Berberine: The Top Supplement for Health Benefits and Wellness

Overall Health Benefits of Berberine

Berberine benefits include its ability to improve insulin sensitivity, regulate blood sugar levels, decrease inflammation, and reduce cholesterol levels, making it a powerful supplement for managing diabetes, PCOS symptoms, and promoting cardiovascular and digestive health. Additionally, it possesses potential anti-cancer properties by decreasing sugar production in the liver and fighting various cancer types.

Lowers blood sugar levels [1-62]
Decreases inflammation [63-88]
Treats PCOS symptoms [89-117]
Reduces cholesterol levels [118-137]
Improves digestive health [138-161]
Decreases sugar production in the liver [162-182]
Fights cancer [183-242]

Key Takeaways

Berberine is a bioactive compound found in several plants, including goldenseal, barberry, and Chinese goldthread. It has a long history of use in traditional medicine, particularly in Chinese and Ayurvedic practices.
Berberine has been studied for its potential to help regulate blood sugar levels. Research suggests that it may improve insulin sensitivity, making it beneficial for individuals with type 2 diabetes or those at risk of developing the condition.
Studies have indicated that berberine may have positive effects on cardiovascular health. It has been associated with lowering levels of LDL cholesterol and triglycerides, potentially reducing the risk of cardiovascular diseases.
Berberine exhibits anti-inflammatory properties, which can be beneficial in managing various inflammatory conditions. This includes potential applications in joint health and inflammatory disorders.
Berberine has antimicrobial properties and may be effective against a variety of microorganisms, including bacteria, viruses, fungi, and parasites. This makes it a topic of interest for potential applications in managing infections.

What is Berberine?

Berberine is a bioactive compound found in several plants, including goldenseal, barberry, and Chinese goldthread. With a history of use in traditional medicine, particularly in Chinese and Ayurvedic practices, berberine has gained attention for its potential health benefits. It is studied for its ability to regulate blood sugar levels, improve insulin sensitivity, promote cardiovascular health by lowering cholesterol and triglycerides, exhibit anti-inflammatory properties, and demonstrate antimicrobial activity against various microorganisms. While research is ongoing, berberine shows promise in addressing several health concerns and is commonly used as a dietary supplement.

How Berberine Works

Berberine, a bioactive compound found in several plants, works through multiple mechanisms in the body. One of its primary actions involves activating AMP-activated protein kinase (AMPK), a regulator of cellular energy metabolism. This activation enhances glucose uptake in cells, leading to improved insulin sensitivity and regulation of blood sugar levels. Berberine also influences various pathways related to lipid metabolism, contributing to lowered cholesterol and triglyceride levels. Moreover, it exhibits anti-inflammatory effects by modulating specific signaling pathways. Additionally, berberine possesses antimicrobial properties, making it effective against various infections. The diverse range of actions makes berberine a promising natural compound with potential therapeutic benefits for conditions like diabetes, cardiovascular issues, inflammation, and infections.

Chemical Structure of Berberine

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Research on Berberine

A. Improves Blood Sugar Levels

Berberine not only improves blood sugar levels by enhancing insulin sensitivity, increasing glycolysis (the breakdown of glucose within cells), decreasing glucose production in the liver, and promoting the uptake of glucose into the cells but also stands out among diabetes medications. Its mechanism of action is notably similar to that of pharmaceuticals such as metformin, a widely used diabetes drug. This similarity positions berberine as a compelling natural alternative for managing blood sugar levels in individuals with type 2 diabetes or those aiming to regulate their glucose levels effectively. By offering a plant-based option, berberine enriches the arsenal of tools available to treat diabetes, providing patients and healthcare providers with more versatility in tailoring diabetes management plans to individual needs.

Berberine inhibits preadipocyte differentiation and secretion of key adipokines, resulting in improved insulin sensitivity and metabolic parameters in both human preadipocytes and metabolic syndrome patients treated with berberine for three months. [1]
In this randomized clinical trial, berberine administration resulted in significant improvements in metabolic syndrome markers, including remission of metabolic syndrome, decreased waist circumference, triglycerides, and total insulin secretion, along with increased insulin sensitivity, compared to placebo. [2]
Berberine, a plant alkaloid, exhibits diverse health benefits including prevention of atherosclerosis, type 2 diabetes, obesity, cardiovascular complications, and cancer. It positively influences blood glucose levels, insulin resistance, glycolysis, and insulin secretion, while inhibiting gluconeogenesis, adipogenesis, and LDL levels, and demonstrating anti-inflammatory, neuroprotective, and anticancer properties, making it a promising nutraceutical for various health conditions. [3]
Berberine, derived from Coptidis rhizome, has been found effective in improving vascular insulin sensitivity and vasodilatation in diabetic rats, possibly through up-regulation of insulin receptor-mediated signalling pathways and enhanced endothelial function. [4]
A recent finding highlight berberine’s potential as a preventive or adjunctive therapy for diabetic vascular complications, supported by its ability to restore impaired vasodilatation and enhance insulin-induced vasodilatation in mesenteric arteries. [5]
In a recent study, researchers evaluated the effectiveness of a new bioavailable berberine 5formulation in normal-overweight PCOS women with normal menses, finding significant improvements in insulin resistance, inflammation markers, lipid metabolism, sex hormone profile, and symptoms associated with hyperandrogenism after 60 days of supplementation. These findings suggest that berberine could serve as a safe and promising dietary supplement for managing PCOS-related symptoms and metabolic dysregulation. [6]
Berberine’s effects on preadipocytes from human omental fat and in metabolic syndrome patients were investigated in this study, revealing significant inhibition of preadipocyte differentiation and changes in adipokine profile. The findings suggest that berberine may improve insulin sensitivity by modulating fat storage and adipokine secretion in both preadipocytes and metabolic syndrome patients. [7]
In this study, researchers investigated the impact of berberine (BBR) on the LTB4-BLT1 axis, a key pathway implicated in chronic low-grade inflammation and insulin resistance. Their findings suggest that BBR may mitigate inflammation and insulin resistance by modulating the LTB4-BLT1 signaling pathway, potentially offering a novel anti-inflammatory and anti-diabetic mechanism of action. [8]
In this systematic review and meta-analysis, the efficacy and safety of berberine in treating patients with type 2 diabetes mellitus (DM) were evaluated across forty-six trials, demonstrating significant improvements in glycemic metabolism, insulin resistance, lipid profiles, and inflammation markers. The findings suggest that berberine, particularly as an adjunctive therapy, holds promise for managing type 2 DM and dyslipidemia, potentially informing targeted clinical approaches and the development of novel medications in the future. [9]
In this study, the researchers aimed to investigate the impact of berberine (BBR) on glucose metabolism in cardiomyocytes, particularly focusing on its effects on glucose consumption and uptake in insulin-sensitive and insulin-resistant rat H9c2 cells. Their findings suggest that BBR increases glucose consumption and uptake in both insulin-sensitive and insulin-resistant cardiomyocytes, potentially through activation of AMP-activated protein kinase (AMPK) signaling, highlighting its potential role in improving insulin resistance in diabetic cardiomyopathy. [10]
Excessive glucocorticoid (GC) production leads to obesity and insulin resistance via glucocorticoid receptor (GR) activation, yet the molecular mechanisms underlying GC’s non-genomic effects on the insulin-signalling pathway in skeletal muscle remain unclear. Here, we investigated how Huang-Gui solid dispersion (HGSD), a highly bioavailable berberine formulation, ameliorated GR-mediated alterations in PI3K signalling and insulin resistance in diabetic rats, dexamethasone-treated mice, and insulin-resistant C2C12 skeletal muscle cells, suggesting HGSD’s potential as a promising treatment for type 2 diabetes by mitigating excess GC-induced insulin resistance through modulation of GR-PI3K association in skeletal muscle. [11]
Berberine (BBR) was found to alleviate insulin resistance (IR) induced by intralipid infusion in rats, independent of changes in blood glucose levels, and this effect was associated with reduced mitochondrial swelling in skeletal muscle. Furthermore, BBR’s beneficial impact on IR was mediated primarily through skeletal muscle, as demonstrated by its suppression of intralipid-induced upregulation of cyclophilin D (CypD) expression in skeletal muscle cells. [12]
Berberine was found to effectively improve insulin sensitivity in fructose-fed mice, as evidenced by significant reductions in fasting insulin levels and area under the curve during oral glucose tolerance test (OGTT), accompanied by favorable changes in serum leptin and adiponectin levels. Mechanistically, berberine increased phosphorylation levels of protein kinase B (AKT) and glycogen synthase kinase-3β (GSK3β), enhanced hepatic glycogen content, and upregulated the expression of key proteins involved in energy metabolism, suggesting its potential therapeutic application for insulin resistance treatment. [13]
A study investigated the metabolic effects of berberine in two animal models of insulin resistance and insulin-responsive cell lines, revealing its ability to reduce body weight, improve glucose tolerance, and enhance insulin action without affecting food intake in diabetic mice and high-fat-fed rats. Furthermore, berberine demonstrated downregulation of lipogenesis-related genes and upregulation of energy expenditure-related genes in adipose tissue and muscle, along with increased AMP-activated protein kinase (AMPK) activity in adipocytes and myotubes, suggesting its potential therapeutic role in diabetes and obesity through AMPK stimulation. [14]
A study examined the metabolic effects of berberine in two animal models of insulin resistance and insulin-responsive cell lines, revealing its ability to improve glucose tolerance, reduce body weight, and enhance insulin action without altering food intake in diabetic mice and high-fat-fed rats. Additionally, berberine stimulated AMP-activated protein kinase (AMPK) activity in adipocytes and myotubes, suggesting its potential as a therapeutic agent for diabetes and obesity by modulating key metabolic pathways. [15]
A study investigated the molecular mechanism and therapeutic potential of berberine in nonalcoholic fatty liver disease (NAFLD). Berberine treatment significantly improved insulin resistance in NAFLD rats by up-regulating IRS-2 mRNA and protein levels, suggesting its potential as a treatment for NAFLD. [16]
A study explored how berberine enhances vascular insulin sensitivity in diabetic rats. Berberine treatment significantly restored impaired vasodilation in mesenteric arteries, up-regulated insulin receptor-mediated signaling, and improved vascular function, suggesting its potential as a treatment for diabetic vascular complications. [17]
A study aimed to explore how berberine affects insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes. Berberine treatment reversed the inhibitory effects of FFAs on insulin-stimulated glucose transport, reduced IKKβ and IRS-1 phosphorylation, and prevented nuclear translocation of NF-κB p65, suggesting its potential in improving insulin resistance by targeting IKKβ. [18]
A study aimed to investigate the potential of berberine in slowing the progression of diabetic retinopathy (DR) in insulin-treated patients by examining its effect on retinal expression of HIF-1α and VEGF through the AKT/mTOR pathway. Berberine demonstrated a dose- and time-dependent inhibition of insulin-stimulated HIF-1α and VEGF expression in retinal endothelial cells, suggesting its efficacy as an adjuvant therapy for DR in both type I and type II diabetes. [19]
Berberine lowers blood sugar levels through multiple mechanisms. [20-62] It activates an enzyme called AMP-activated protein kinase (AMPK), which is often referred to as a metabolic master switch, leading to improved insulin sensitivity and enhanced glucose uptake by the cells. Berberine also inhibits the production of glucose in the liver, a process known as gluconeogenesis. Additionally, it increases the number and activity of insulin receptors, further facilitating glucose absorption by the cells and reducing blood sugar levels. These actions collectively mimic the effects of insulin and help in the management of type 2 diabetes by improving glucose regulation in the body.

B. Decreases Inflammation

Berberine decreases inflammation by inhibiting the production and activity of pro-inflammatory molecules, such as cytokines and enzymes like cyclooxygenase-2 (COX-2). It acts on molecular pathways, including the NF-kB pathway, which plays a crucial role in the inflammatory process. Through these mechanisms, berberine helps reduce inflammation in the body, contributing to its potential benefits in various inflammatory and metabolic conditions.

In a meta-analysis of randomized controlled trials, berberine’s effects on inflammatory markers in metabolic syndrome (MetS) and related disorders were systematically evaluated. [63] Among 52 included studies involving 4616 patients, berberine significantly reduced levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) but had no significant effect on interleukin 1β (IL-1β).
In one study, the effects of berberine on experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, were investigated in female C57BL/6 mice. [64] Berberine administration at low and high doses significantly reduced clinical scores compared to the control group, showing lower lymphocyte infiltration and demyelination in the CNS. Treatment with berberine also decreased pro-inflammatory cytokines while increasing anti-inflammatory cytokine expression, suggesting its potential as a protective agent in EAE by enhancing Treg and Th2 cell function alongside its anti-inflammatory properties.
A study aimed to assess the impact of berberine (BBR) on the intestinal health of piglets exposed to deoxynivalenol (DON). [65] Piglets were divided into three groups: basal diet, basal diet with DON, and basal diet with DON and BBR. Results showed that BBR improved growth performance and inhibited DON-induced intestinal injury by enhancing antioxidant enzyme expression, T cell surface antigens, and reducing proinflammatory cytokines. BBR also increased protein expression levels of tight junction proteins in the mucosa and improved morphological parameters of the jejunum. Furthermore, BBR reduced the expression of signaling pathways associated with inflammation and oxidative stress, suggesting its potential in maintaining intestinal health in piglets exposed to DON.
Chronic low-grade inflammation is a significant factor in insulin resistance, often exacerbated by leukotriene B4 (LTB4) binding to its receptor BLT1, intensifying inflammation and insulin resistance. [66] Berberine (BBR) has known anti-inflammatory properties, but its effect on the LTB4-BLT1 axis remains unclear. Through experiments using LTB4-induced Raw264.7 and HepG2 cells, BBR was found to mitigate inflammation and insulin resistance. These findings suggest that BBR may interact with BLT1, potentially modulating the LTB4-BLT1 pathway, offering a novel anti-inflammatory and anti-diabetic mechanism for BBR.
Berberine (BBR), an isoquinoline alkaloid with diverse pharmacological effects, exhibits anti-adipogenic properties whose mechanism remains elusive. [67] In this investigation, researchers treated 3T3-L1 cells with varying concentrations of BBR to analyze changes in adipogenic enzyme expression. BBR treatment led to reduced levels of leptin and adipogenic factors, alongside increased glycerol secretion and slightly decreased lipolytic enzyme mRNA expression. Furthermore, BBR treatment resulted in down-regulation of inflammation markers such as TNF-alpha and IL-6.
Berberine, an isoquinoline alkaloid with diverse pharmacological effects, including anti-inflammatory properties, presents an unclear mechanism of action. [68] Given the role of cyclooxygenase-2 (COX-2) in prostaglandin synthesis, elevated during inflammation, researchers investigated whether berberine’s anti-inflammatory mechanism involves COX-2 regulation. In oral cancer cell lines OC2 and KB cells, berberine treatment reduced prostaglandin E2 (PGE2) production in a dose-dependent manner, with or without induction by 12-O-tetradecanoylphorbol-13-acetate (TPA). Berberine rapidly decreased COX-2 protein levels within 3 hours, without affecting enzyme activity, and inhibited activator protein 1 (AP-1) binding within 2 hours, suggesting direct AP-1 inhibition. In vivo, berberine pretreatment in Wistar rats inhibited exudate and PGE2 production in carrageenan-induced air pouches, reinforcing its anti-inflammatory effects.
A review summarized BBR’s antioxidant and anti-inflammatory actions, evidenced by changes in oxidative stress markers, antioxidant enzymes, and proinflammatory cytokines in diabetic animals. [69] BBR mitigates oxidative stress and inflammation in various tissues, including liver, adipose tissue, kidney, and pancreas. Its mechanisms involve multiple cellular kinases and signaling pathways, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2), and nuclear factor-κB (NF-κB).
A study aimed to compare the anti-inflammatory potential of BBR and its natural derivatives, oxyberberine (OBB) and dihydroberberine (DHBB), both in vitro and in vivo, and elucidate their underlying mechanisms. [70] LC-MS/MS analysis confirmed the presence of BBR, OBB, and DHBB in RC extract. In vitro assays revealed that pretreatment with BBR, OBB, and DHBB significantly reduced pro-inflammatory cytokines and inhibited NF-κB signaling pathway activation, with OBB demonstrating the highest efficacy. In vivo, BBR and OBB pretreatment dose-dependently alleviated inflammation in murine models, with OBB showing superior efficacy. Histopathological analysis supported the anti-inflammatory effects of OBB and BBR.
A study investigated berberine’s efficacy in treating dextran sulfate sodium (DSS)-induced intestinal injury and colitis in mice. [71] Berberine administration alleviated DSS-induced symptoms including body weight loss, colon shortening, and inflammation. It also reduced proinflammatory cytokine levels, preserved barrier function, and inhibited apoptosis in colonic epithelium. Additionally, berberine suppressed proinflammatory cytokine production and signaling pathways activation in colonic macrophages and epithelial cells.
A study aimed to investigate berberine’s impact on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its underlying mechanisms. [72] Berberine treatment significantly reduced footpad swelling, inflammatory cell infiltration, anti-OVA IgG levels, serum IgE concentration, and tetramer+CD8+ cells. It suppressed Th1-mediated cytokine production in footpad tissue, particularly IFN-γ, TNF-α, and IL-2. Berberine inhibited differentiation into Th1 cells by suppressing T-bet expression and IFN-γ secretion without affecting IL-4. Furthermore, berberine reduced lymphocyte proliferation and cytotoxicity while decreasing apoptosis and caspase-3 activity, as evidenced by altered Bax/Bcl-2 ratio and cleaved caspase-3 expression.
Berberine decreases inflammation through multiple mechanisms, primarily by inhibiting the activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a protein complex that plays a key role in regulating the immune response to infection. [73-88] By suppressing NF-κB activation, berberine reduces the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which are involved in the inflammatory process. Additionally, berberine has been shown to activate the AMP-activated protein kinase (AMPK) pathway, which contributes to its anti-inflammatory effects by promoting cellular energy homeostasis and reducing oxidative stress, further inhibiting inflammatory responses at the cellular level.

C. Treats PCOS Symptoms

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Berberine is increasingly recognized for its role in managing Polycystic Ovary Syndrome (PCOS), primarily by targeting the syndrome’s root issues such as insulin resistance. This condition, prevalent among those with PCOS, is crucial for berberine’s effectiveness in regulating menstrual cycles and promoting ovulation. Furthermore, berberine’s anti-inflammatory and anti-androgen properties are beneficial for reducing common PCOS symptoms like acne and excessive hair growth. Its capacity to aid in weight loss and enhance lipid profiles addresses the metabolic complications often seen in polycystic ovary syndrome patients. Consequently, berberine emerges as a promising supplement for those seeking to mitigate the diverse symptoms associated with PCOS, offering a multifaceted approach to managing this complex condition.

Polycystic ovary syndrome (PCOS), affecting 5-10% of women of reproductive age, was first detailed by Stein and Leventhal in 1935. Given its diverse symptomatology, PCOS treatment often involves tailored approaches and multiple medications. Berberine, a well-established alkaloid, has emerged as a promising treatment for PCOS. Studies suggest it can alleviate hormonal imbalances, including reducing testosterone levels and FAI, increasing SHBG, and improving symptoms like hirsutism and acne. [89-90] Berberine also enhances the effects of other PCOS drugs like metformin and oral contraceptives, with generally good tolerability.
A study assessed the impact of berberine (BBR) on polycystic ovary syndrome (PCOS) patients with insulin resistance (IR). [91] A systematic search of multiple databases was conducted up to July 2018 to identify relevant randomized controlled trials. Nine studies were included in the analysis. The findings suggested that while berberine (BBR) did not significantly differ from metformin (MET) in alleviating insulin resistance or improving glycolipid metabolism and reproductive endocrine conditions, combinations of BBR with cyproterone acetate (CPA) or Chinese herbs showed potential benefits.
Polycystic ovary syndrome (PCOS) is a complex disorder characterized by various endocrine and metabolic irregularities, leading to fertility challenges and adverse pregnancy outcomes. Insulin resistance, often accompanying PCOS, contributes to these complications. Berberine, a compound found in medicinal herbs, possesses hypoglycemic properties and has shown promise in improving fertility and pregnancy outcomes in PCOS women with insulin resistance. [92]
A evaluated the impact of Berberine (BBR) on women’s health, particularly focusing on its effects on polycystic ovary syndrome (PCOS) patients, providing valuable insights for both patients and healthcare providers. [93] Through a comprehensive search of electronic databases up to July 1st, 2019, including PubMed, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL), clinical trials and randomized controlled trials assessing the effects of BBR on PCOS were identified. While BBR did not significantly affect body weight and composition, it showed a notable decrease in waist to hip ratio (WHR), hormonal profiles related to insulin resistance (IR), and insulin resistance itself (HOMA-IR). Additionally, androstenedione levels decreased significantly with BBR treatment, although no significant effects were observed on follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
A study evaluated the potential of berberine in managing polycystic ovary syndrome (PCOS), considering its effectiveness against insulin resistance and obesity, particularly in reducing visceral adipose tissue (VAT). [94] The review encompasses five studies involving a total of 1078 women, revealing promising results. Berberine was found to induce a redistribution of adipose tissue, improve insulin sensitivity similar to metformin, enhance lipid patterns, and ameliorate insulin resistance in theca cells, leading to improved ovulation rates and fertility outcomes. Overall, berberine appears to be safe for premenopausal women seeking pregnancy with minimal side effects. Further research is warranted to establish optimal dosage for long-term therapy.
Berberine treats Polycystic Ovary Syndrome (PCOS) by addressing several underlying mechanisms associated with the condition. [95-117] It improves insulin sensitivity, which is crucial since insulin resistance is a common issue in PCOS, helping to regulate blood sugar levels and potentially reduce the risk of developing type 2 diabetes. Berberine also influences lipid metabolism, contributing to lower cholesterol levels and aiding in weight management, which is beneficial for PCOS patients struggling with obesity. Additionally, berberine has been shown to affect hormonal balance, including reducing testosterone levels, which can help alleviate symptoms like acne and hirsutism. Through these actions, berberine targets key aspects of PCOS, offering a multi-faceted approach to managing the condition.

D. Reduces Cholesterol Levels

Berberine is particularly beneficial for individuals with high cholesterol, as it directly impacts blood lipids by reducing cholesterol levels through the inhibition of an enzyme called PCSK9. This results in more LDL (low-density lipoprotein) cholesterol, often referred to as “bad” cholesterol, being removed from the bloodstream. Furthermore, berberine enhances the liver’s ability to extract LDL cholesterol from the blood for conversion into bile acids, thereby lowering overall cholesterol levels. This mechanism is crucial for those struggling with high cholesterol, as it can lead to a significant improvement in their cholesterol profiles and reduce the risk associated with cardiovascular diseases. Berberine’s multifaceted approach to managing blood lipids makes it an effective option for improving cholesterol profiles and supporting cardiovascular health, offering a natural alternative for managing high cholesterol and protecting against heart disease.

A study aimed to review berberine’s efficacy and safety for dyslipidemia treatment, considering potential sex disparities. [118] Eighteen studies (n = 1788 participants) mainly from mainland China and Hong Kong were analyzed. Berberine reduced LDL cholesterol, total cholesterol, triglycerides, and apolipoprotein B, while increasing HDL cholesterol. Notably, the effect on HDL cholesterol differed between women and men.
While statins effectively lower LDL-cholesterol levels and reduce coronary artery disease-related mortality and morbidity, residual risk remains. Berberine, through a distinct mechanism involving stabilization of LDL receptor mRNA, also lowers LDL-cholesterol levels. [119]
In a study involving 32 hypercholesterolemic patients, oral administration of BBR for 3 months resulted in a 29% reduction in serum cholesterol, a 35% decrease in triglycerides, and a 25% decrease in LDL-cholesterol. [120] Treatment of hyperlipidemic hamsters with BBR showed a significant decrease in serum cholesterol by 40% and LDL-cholesterol by 42%, accompanied by substantial increases in hepatic LDL receptor (LDLR) mRNA and protein levels.
In a randomized, double-blind, placebo-controlled trial in Hong Kong involving 84 Chinese men with hyperlipidemia, berberine (500 mg orally, twice a day) or placebo was administered for 12 weeks. [121] Berberine exhibited larger reductions in total cholesterol and high-density lipoprotein cholesterol after 12 weeks, potentially altering low-density lipoprotein-cholesterol (LDL-c) and testosterone levels.
Research design and methods involved 144 Caucasian subjects who underwent a 6-month run-in period of diet and physical activity before randomization to receive placebo or berberine 500 mg twice daily for 3 months in a double-blind, placebo-controlled design. [122] After a 2-month washout period with only diet and physical activity, patients resumed either berberine or placebo for another 3 months. Anthropometric and metabolic parameters were evaluated throughout the study. Results showed a decrease in body weight and BMI after the run-in period, with berberine significantly reducing total cholesterol, triglycerides, and LDL cholesterol, while increasing HDL cholesterol compared to placebo.
Several studies have shown that berberine can significantly reduce LDL cholesterol levels, often referred to as “bad” cholesterol because high levels can lead to plaque buildup in the arteries and increase the risk of heart disease. [123- 137] It can activate an enzyme called AMP-activated protein kinase (AMPK), which plays a role in regulating lipid metabolism. By activating AMPK, berberine helps reduce the synthesis of cholesterol in the liver, increase the removal of LDL (low-density lipoprotein) cholesterol, and decrease triglyceride levels.

E. Improves Digestive Healt

Berberine improves digestive health by exhibiting antimicrobial properties that can balance the gut microbiota, selectively targeting harmful pathogens while sparing beneficial bacteria. This ability to maintain and even promote the growth of beneficial bacteria in the gut reduces inflammation within the gastrointestinal tract. It aids in managing symptoms related to various digestive disorders, such as irritable bowel syndrome (IBS) and intestinal infections, by promoting the healing of the gut lining and potentially reducing the occurrence of diarrhea. Unlike many prescription medications that may have side effects, berberine offers a natural alternative with multiple benefits for digestive health. This natural compound’s ability to enhance barrier function and modulate gut flora, thereby fostering a healthy population of beneficial bacteria, makes it beneficial for overall digestive health, presenting an option for those seeking alternatives to traditional prescription medications for managing digestive disorders.

A study assessed the impact of berberine (BBR) on liver phosphatidate phosphohydrolase (PAP) activity and plasma lipid levels in rats fed high lipogenic and normal diets. [138] Forty rats were divided into five groups receiving different diet and treatment combinations. Results showed that BBR supplementation significantly reduced PAP activity, plasma triglyceride, total cholesterol, very low-density lipoprotein, and malondialdehyde levels compared to the lipogenic diet group. Moreover, BBR led to a notable decrease in liver triglyceride and cholesterol levels, as well as in the atherogenic index, suggesting its potential effectiveness in mitigating lipid abnormalities and liver triglyceride accumulation associated with hyperlipidemia, with minimal side effects.
Berberine, a traditional Chinese remedy, has shown promise in treating various diseases like obesity, diabetes, and atherosclerosis, with ongoing clinical trials exploring its potential in cardiovascular, gastrointestinal, and endocrine disorders. [139] Despite its clinical benefits and low toxicity, the precise mechanism behind its lipid-lowering and insulin-sensitizing effects remains unclear. One plausible explanation is its impact on the gastrointestinal microbiota.
Berberine (BBR), an isoquinoline alkaloid abundant in plants like Coptis chinensis Franch, exhibits limited bioavailability but exerts significant influence on various diseases by interacting with the gut microbiota. [140] Its impact spans conditions including diabetes, hyperlipidemia, atherosclerosis, liver and intestinal diseases, mental disorders, and autoimmune diseases.
Recent research highlights the intricate connection between the gut microbiome and various metabolic diseases such as obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. [141] Berberine (BBR), a natural compound, has emerged as a significant therapeutic agent for metabolic disorders, with studies demonstrating its ability to alleviate pathological conditions. This effect is attributed to BBR’s regulation of the gut microbiota, influencing its absorption, utilization, and structural composition.
Reseachers investigated the impact of berberine (BBR), a natural alkaloid, on intestinal bacteria using in vitro and in vivo models. [142] In vivo, short-term BBR exposure led to alterations in intestinal bacteria, notably reducing Clostridium clusters XIVa and IV and their bile salt hydrolase (BSH) activity, resulting in taurocholic acid (TCA) accumulation and subsequent FXR activation. In vitro, BBR exposure directly affected bacterial physiology, composition, and function, particularly reducing BSH-expressing bacteria like Clostridium spp. These findings highlight BBR’s direct influence on bacterial communities, shedding light on its role in bile acid metabolism and FXR signaling modulation, thus providing novel insights into the interplay between intestinal bacteria, nuclear receptor signaling, and xenobiotics.
Studies suggest that berberine, a compound found in several plants, can improve digestive health through various mechanisms. [143-161] Its antimicrobial properties may help regulate gut flora, reducing the growth of harmful bacteria and potentially alleviating symptoms of gastrointestinal infections and disorders. Berberine has also been shown to enhance gut barrier function, which can help in preventing leaky gut syndrome and reducing inflammation. Additionally, its ability to stimulate bile secretion and modulate gut motility contributes to improved digestion and relief from constipation. These findings highlight berberine’s potential as a beneficial supplement for supporting digestive health.

F. Decreases Sugar Production in the Liver

Berberine decreases sugar production in the liver primarily by activating an enzyme called AMP-activated protein kinase (AMPK). AMPK is often referred to as a metabolic master switch because it plays a crucial role in regulating metabolism. When activated by berberine, AMPK inhibits the production of glucose in the liver through a process known as gluconeogenesis. This action helps lower blood sugar levels in individuals with high blood sugar, making berberine a valuable supplement for managing conditions like type 2 diabetes. By targeting the liver’s glucose production directly, berberine can effectively reduce fasting blood sugar levels and improve overall glucose tolerance.

Dysregulated glucagon levels contribute to hepatic glucose overproduction, a primary driver of persistent hyperglycemia in type 2 diabetes. [162] While berberine (BBR) has been recognized for its hypoglycemic effects, the precise mechanism by which it inhibits hepatic gluconeogenesis remains unclear. In this study, diabetic mice treated with BBR showed improved blood glucose levels, insulin and glucose tolerance, and suppressed hepatic gluconeogenesis induced by lactate and glucagon. BBR also attenuated glucagon-induced glucose production and gluconeogenic gene expression in hepatocytes by reducing intracellular cAMP levels and inhibiting downstream CREB phosphorylation. Further investigations using cAMP-modifying agents revealed that BBR accelerates cAMP degradation by activating phosphodiesterase (PDE), thereby blocking CREB activation and downregulating gluconeogenic genes, ultimately restraining hepatic glucose production.
Berberine (BBR), derived from the Chinese herb Huanglian (Coptis chinensis French), enhances glucose metabolism in type 2 diabetic patients by activating adenosine monophosphate-activated protein kinase (AMPK) and improving insulin sensitivity. [163] However, its additional mechanisms remain unclear. In this study, we investigated BBR’s impact on liver response in diabetic rats induced by a high-fat diet. BBR significantly reduced fasting glucose levels and suppressed the expression of gluconeogenic genes (PEPCK and G6Pase) in the liver. Additionally, BBR reduced hepatic steatosis and inhibited the expression of fatty acid synthase (FAS), along with decreasing the activities of transcription factors (FoxO1, SREBP1, and ChREBP).
Berberine is known to inhibit hepatic gluconeogenesis, yet the underlying mechanism remains unclear. [164] This study investigated whether berberine could reduce excessive hepatic glucose production (HGP) by targeting mitochondrial pyruvate import through MPC1. High-fat diet (HFD) feeding increased HGP, hepatic acetyl CoA accumulation, and pyruvate carboxylase (PC) induction. Berberine mitigated acetyl CoA accumulation by limiting fatty acid oxidation and prevented mitochondrial pyruvate shift from oxidation to gluconeogenesis.
Berberine has demonstrated efficacy in regulating glucose and lipid metabolism both in vitro and in vivo. [165] This pilot study aimed to assess the effectiveness and safety of berberine in treating patients with type 2 diabetes mellitus (T2DM). In study A, newly diagnosed T2DM patients were randomly assigned to receive either berberine or metformin for three months. Berberine showed similar hypoglycemic effects to metformin, with significant reductions observed in hemoglobin A1c, fasting and postprandial blood glucose levels, and plasma triglycerides.
The effects of berberine on glucose-lipid metabolism, inflammatory factors, and insulin resistance were examined in patients with metabolic syndrome. [166] Eighty patients from Linyi Central Hospital were divided into a control group (n=40) and an observation group (n=40). While the control group received standard Western medicine treatment, the observation group received additional berberine therapy. Changes in relevant blood glucose and lipid metabolism indexes, as well as inflammatory factors, were compared between the two groups. At one month post-treatment, both groups exhibited reductions in fasting blood glucose, postprandial blood glucose, insulin resistance index, and blood lipid levels compared to one week post-treatment (P<0.05). Additionally, the observation group showed significantly lower levels of these parameters compared to the control group (P<0.05). Furthermore, levels of inflammatory markers (hs-CRP, IL-6, TNF-α) decreased in both groups after one month, with the observation group exhibiting lower levels compared to the control group.
Studies suggest that berberine acts similarly to certain pharmaceuticals by influencing molecular pathways to reduce hepatic glucose production. [167-182] Specifically, it activates an enzyme called AMP-activated protein kinase (AMPK), often referred to as a cellular energy regulator. By activating AMPK, berberine can decrease the expression of genes involved in gluconeogenesis, the process by which the liver produces glucose. This action helps lower fasting blood glucose levels and improves overall glucose metabolism, making berberine a subject of interest for managing type 2 diabetes and insulin resistance.

G. Fights Cancer

Berberine fights cancer through multiple mechanisms, including inhibiting cancer cell growth and proliferation, inducing apoptosis (programmed cell death) in cancer cells, and disrupting the cell cycle of cancerous cells. It also impedes the spread of cancer by inhibiting angiogenesis (the formation of new blood vessels that feed tumors) and metastasis (the spread of cancer cells to new areas). Additionally, berberine has been shown to enhance the sensitivity of cancer cells to chemotherapy and radiotherapy, making these treatments more effective. Its anti-inflammatory and antioxidant properties further contribute to its anticancer effects, showcasing its potential as a complementary therapy in cancer treatment.

Berberine (BBR) is a potent plant-derived compound with significant anticancer effects, drawing attention from extensive in vitro and in vivo studies. [183] Its anticancer mechanisms involve targeting various molecular pathways, including activation of p53 and modulation of Cyclin B to arrest cell cycles, inhibition of protein kinases like AKT and MAP kinase for antiproliferative activity, and regulation of autophagy through beclin-1. Berberine also impedes invasion and metastasis by reducing MMP-9 and MMP-2 expression and inhibits oncogene expression by interfering with AP-1 activity. Furthermore, it hampers carcinogenesis by modulating enzymes such as N acetyl transferase, Cyclo-oxygenase-2, Telomerase, and Topoisomerase, while regulating reactive oxygen species and inflammatory cytokines.
Berberine (BBR), a potent bioactive compound, holds considerable promise for various health benefits, particularly in combating cancer. [184] This review synthesizes extensive research highlighting BBR’s anticancer properties across multiple cancer types, including colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR exhibits anti-proliferative effects by inducing apoptosis, regulating the cell cycle, and modulating autophagy. It also impedes tumor invasion and metastasis by suppressing metastasis-related proteins and inhibiting epithelial-mesenchymal transition.
Cancer presents a significant public health challenge, prompting extensive research into potential treatments. [185] Berberine, a renowned natural compound derived from medicinal herbs, exhibits diverse bioactivities, including antioxidant, anti-inflammatory, antidiabetic, anti-obesity, and antimicrobial properties. Notably, berberine demonstrates promising anticancer effects across various cancer types, including breast, lung, gastric, liver, colorectal, ovarian, cervical, and prostate cancers. Mechanisms of action involve inhibition of cancer cell proliferation, metastasis suppression, apoptosis induction, autophagy activation, modulation of gut microbiota, and enhancement of anticancer drug effects.
Cancer remains a pervasive global health challenge, necessitating novel treatment approaches to improve outcomes and mitigate side effects. [186] Natural compounds from medicinal plants, such as berberine, have garnered attention for their potential anticancer properties. Berberine, an alkaloid present in various plants, demonstrates anticancer effects by scavenging free radicals, inducing apoptosis, arresting the cell cycle, inhibiting angiogenesis and inflammation, and modulating signaling pathways like PI3K/AKT/mTOR, Wnt/β-catenin, and MAPK/ERK. Moreover, berberine shows synergistic effects with other anticancer agents.
Extensively studied in both in vivo and in vitro experiments, berberine (BBR) showcases multifaceted anticancer properties. It regulates cell proliferation by modulating the cell cycle, inducing autophagy, and promoting apoptosis while also inhibiting invasion and metastasis through suppression of epithelial-mesenchymal transition (EMT) and metastasis-related proteins and pathways. [187] Additionally, BBR interacts with microRNAs to suppress telomerase activity, exerts anti-inflammatory and antioxidant effects, and modulates the tumor microenvironment.
Studies suggest that berberine, a compound found in several plants, possesses anti-cancer properties through multiple mechanisms. [188-242] It has been shown to inhibit cancer cell growth, induce apoptosis (programmed cell death), and prevent the spread of cancer cells. Berberine acts on various signaling pathways involved in cancer progression, including those regulating cell cycle, metastasis, and angiogenesis (the formation of new blood vessels that feed tumors). Its ability to modulate these pathways contributes to its potential as a complementary therapy in cancer treatment. However, despite promising preclinical data, more research, including clinical trials, is needed to fully understand its efficacy and safety in cancer therapy.

H. Treats High Blood Pressure

Berberine treats high blood pressure by improving overall cardiovascular health through mechanisms such as enhancing arterial flexibility, reducing inflammation, and helping to control lipid levels and body weight. Its effects on metabolic health, including improving insulin sensitivity and reducing blood sugar levels, also contribute indirectly to blood pressure management by addressing underlying conditions that can lead to hypertension.

In this randomized, double-blind, placebo-controlled clinical trial involving 24 patients with metabolic syndrome, berberine administration resulted in a significant reduction in waist circumference, systolic blood pressure, triglycerides, and insulin secretion, alongside an increase in insulin sensitivity. [2] These findings suggest that berberine may contribute to the remission of metabolic syndrome and improvements in various metabolic parameters.
In one study, the effects of berberine on blood pressure reduction and vascular protection in diabetic rats were investigated. [40] Berberine was administered intragastrically at varying dosages to diabetic rats for 8 weeks, following streptozotocin injection. The results showed that chronic administration of 100 mg/kg/day of berberine not only lowered blood glucose levels but also reduced blood pressure and improved vasodilation in diabetic rats.
To address the ongoing debate surrounding BBR’s efficacy, a meta-analysis was conducted, compiling data from randomized controlled trials (RCTs) up to July 2022. [135] The results revealed that BBR supplementation significantly reduced triglycerides, total cholesterol, low-density lipoprotein, fasting blood glucose, insulin, HbA1c, HOMA-IR, systolic blood pressure, weight, and body mass index, while increasing high-density lipoprotein. Optimal BBR dosage varied for different parameters, with favorable outcomes observed over specific time frames. Overall, BBR supplementation demonstrated improvements in lipid profile, blood glucose regulation, obesity indicators, and blood pressure, suggesting its potential in managing CVD risk factors.

Berberine Supplements

Berberine supplements have gained popularity for their wide array of health benefits, derived from the berberine compound found in several plants, such as barberry, goldenseal, and tree turmeric. Recognized for its potent bioactive properties, berberine has been extensively studied and shown to improve several key health markers, including lowering blood sugar levels in people with type 2 diabetes, reducing cholesterol, and exhibiting antimicrobial effects against various pathogens. Additionally, berberine’s role in weight management and potential protective effects against cardiovascular diseases further underscore its versatility as a health supplement. Despite its benefits, individuals considering berberine supplements should be aware of potential side effects and interactions with other medications, underscoring the importance of consulting healthcare professionals before incorporating berberine into their health regimen.

Berberine Side Effects

Berberine is a compound found in several plants, including goldenseal, barberry, and Oregon grape. It has been used in traditional medicine for various purposes, and modern research suggests it may have several health benefits, including potential effects on blood sugar levels, cholesterol levels, and inflammation. However, like any supplement or medication, berberine can have side effects, particularly when taken in high doses or over long periods. Some common side effects of berberine supplementation may include:

Gastrointestinal Distress: Berberine may cause gastrointestinal discomfort such as diarrhea, constipation, abdominal pain, and flatulence in some individuals. This is one of the most commonly reported side effects.
Allergic Reactions: Allergic reactions to berberine supplements are possible, although they are relatively rare. Symptoms may include itching, rash, swelling, or difficulty breathing.
Interaction with Medications: Berberine can interact with various medications, including blood thinners, antidiabetic drugs, and medications metabolized by the liver. This can lead to potential complications or reduced effectiveness of these medications.
Liver Toxicity: There are some concerns that high doses of berberine may be toxic to the liver, particularly when used long-term. Individuals with liver disease should exercise caution when using berberine supplements.
Hypotension: Berberine may lower blood pressure, which could be problematic for individuals already taking medications to lower blood pressure or those with hypotension.
Hormonal Effects: Berberine may have effects on hormone levels, particularly insulin and testosterone. While this can be beneficial for some individuals, it may cause unwanted effects in others, especially those with hormonal imbalances.
Interaction with Pregnancy and Breastfeeding: Berberine may not be safe for use during pregnancy or breastfeeding due to limited research on its effects in these populations. It’s best to avoid berberine supplementation during these times unless advised by a healthcare professional.
Electrolyte Imbalance: Berberine may affect potassium levels in the body, potentially leading to electrolyte imbalances, particularly when taken at high doses.

Before beginning berberine supplementation, it’s crucial to seek advice from a healthcare provider, particularly if you’re dealing with any existing health issues or are on medication. They can provide personalized advice based on your health status and help monitor for any potential side effects or interactions.

Berberine Foods

Berberine is a compound found in certain plants, particularly in the roots, stems, and bark. While there aren’t many foods that are rich in berberine, there are some edible plants that contain this compound. Here are a few examples:

Barberry: Barberry is a shrub that produces small, tart berries. The bark and roots of the barberry plant contain berberine. Barberry berries can be used in cooking and baking, and the bark and roots have been used in traditional medicine.
Goldenseal: Goldenseal is a perennial herb native to North America. Its roots and rhizomes contain berberine. Goldenseal has a long history of use in traditional Native American medicine and was used by indigenous peoples for various health purposes.
Oregon Grape: Oregon grape is a shrub native to North America, particularly the Pacific Northwest. Its roots and stem contain berberine. The berries of the Oregon grape plant are edible but are extremely tart and are typically used in small quantities or mixed with sweeter fruits in recipes.
Coptis Chinensis (Chinese Goldthread): This herbaceous perennial plant is native to China and contains high levels of berberine in its rhizomes. In Chinese medicine, it’s used for its various health benefits.

While these plants contain berberine, they are not commonly consumed in large quantities as part of the regular diet. Instead, berberine is often extracted from these plants and used as a supplement in capsule or powder form. It’s important to note that berberine supplements should be used with caution and under the guidance of a healthcare professional, as they can interact with certain medications and may have side effects for some individuals.

Berberine and Metformin

Berberine and metformin are both compounds that have been studied for their potential effects on blood sugar levels and metabolic health, particularly in relation to diabetes management. Here’s an overview of each:

Metformin: Metformin is a medication commonly prescribed to treat type 2 diabetes. It belongs to a class of drugs known as biguanides. Metformin works primarily by decreasing glucose production in the liver and increasing insulin sensitivity in peripheral tissues, such as muscle and fat cells. It also has some effects on reducing glucose absorption in the intestines. Metformin is typically taken orally in the form of tablets or extended-release tablets.
Berberine: Berberine is a naturally occurring compound found in several plants, including goldenseal, barberry, and Oregon grape. It has been used in traditional medicine for various purposes, including the management of diabetes. Berberine has been studied for its potential to lower blood sugar levels, improve insulin sensitivity, and reduce inflammation. It may work through multiple mechanisms, including activation of AMP-activated protein kinase (AMPK), which plays a role in regulating glucose and lipid metabolism. Berberine is available as a dietary supplement in capsule or powder form.

Both metformin and berberine have shown promise in improving glucose metabolism and may be effective in managing blood sugar levels. Some studies have suggested that berberine may be as effective as metformin in lowering blood sugar levels in individuals with type 2 diabetes. Additionally, berberine may have additional benefits, such as reducing lipid levels and inflammation.

However, it’s essential to note that while both metformin and berberine can be effective for some individuals, they may not be suitable for everyone. Both can have side effects, and they may interact with other medications or supplements.

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FAQ

What does berberine do for a person?

Berberine is known to improve several aspects of health, primarily by reducing blood sugar levels and influencing cholesterol levels. By addressing these risk factors, berberine can significantly lower the risk of developing cardiovascular diseases. Additionally, its impact on cholesterol levels helps manage other risk factors associated with heart disease and metabolic syndrome, further enhancing its protective effects on overall health. This makes berberine a potentially valuable supplement for patients undergoing percutaneous coronary intervention (PCI), a common procedure to treat coronary artery disease. Its ability to improve metabolic health may support better outcomes post-PCI by reducing the likelihood of restenosis and promoting overall cardiovascular health.

Is there a downside to taking berberine?

Some potential downsides include gastrointestinal discomfort and interactions with various medications. Additionally, individuals on anticoagulant therapy should be cautious, as berberine may influence blood clotting mechanisms.

Does berberine really work for weight loss?

Berberine has been shown to aid weight loss in some studies, leading to significant weight loss for some individuals, but results may vary. The variability in outcomes highlights the importance of considering individual metabolic responses and lifestyle factors when evaluating berberine’s effectiveness for weight management. Incorporating berberine into a regimen that includes lifestyle changes such as a balanced diet and regular exercise can enhance its weight loss benefits. For those who experience significant weight loss, berberine can be a valuable part of a comprehensive approach to weight management, emphasizing the need for lifestyle changes to achieve and maintain optimal results. This integrated strategy, combining berberine supplementation with lifestyle changes, supports a holistic approach to health and wellness.

Who should not take berberine?

Pregnant women, nursing mothers, and individuals with certain medical conditions should avoid berberine, as its safety in these populations has not been well-established. This is particularly important when considering child health, as substances ingested by pregnant or nursing mothers can affect fetal and infant development. The potential risks to child health necessitate caution and consultation with a healthcare provider before considering berberine for women in these sensitive life stages or for young children.

Does berberine reduce belly fat?

There is evidence suggesting berberine can help reduce belly fat as part of its weight loss benefits.

What is berberine supplement used for?

Berberine supplements are used for managing blood sugar levels, cholesterol, and for potential weight loss benefits.

Will berberine help me lose weight?

Berberine may support weight loss efforts, particularly in conjunction with diet and exercise.

How effective is berberine for weight loss?

Its effectiveness can vary, but berberine has been shown to help with weight loss in several studies.

Is berberine like Ozempic?

Berberine and Ozempic are different; Ozempic is a prescription medication for diabetes, while berberine is a natural supplement with broader uses.

Has anyone gained weight on berberine?

Weight gain is not typically associated with berberine; it is more often linked to weight loss.

What should you not take with berberine?

Avoid taking berberine with medications that are metabolized by the liver, as it can affect drug levels.

Is berberine toxic to the liver?

When taken at recommended doses, berberine is generally not toxic to the liver, but high doses could pose risks, including potential alterations in liver function enzymes.

What does berberine do to kidneys?

Berberine may have protective effects on the kidneys, which is particularly beneficial for individuals managing chronic diseases that can affect kidney health, such as diabetes, hypertension, and idiopathic nephrotic syndrome. However, high doses or long-term use can potentially cause harm. The balance between its therapeutic benefits and risks underlines the importance of cautious use, especially in the context of chronic diseases, where kidney function may already be compromised. Nonetheless, monitoring and consultation with a healthcare provider are essential to safely incorporate berberine into a treatment plan for those with or at risk of chronic diseases.

How long is it safe to take berberine?

Berberine hydrochloride, the commonly used form of berberine for medicinal purposes, is known for its bioavailability and efficacy in managing various health conditions. However, the emphasis on shorter duration usage stems from the cautious approach to mitigate potential side effects and the need for more comprehensive research on its long-term impact, particularly in relation to human development.

What foods contain berberine?

Berberine is found in plants like barberry, goldenseal, and Oregon grape.

What is the best source of berberine?

The best sources of berberine are supplements derived from berberine-rich plants like barberry or goldenseal.

Does turmeric contain berberine?

No, turmeric does not contain berberine; it contains curcumin, a different compound with its own health benefits.

How long does it take for berberine to lower sugar?

Effects on blood sugar levels can be observed as soon as a few days to weeks after starting berberine, a finding supported by numerous studies published in medical journals. These publications highlight berberine’s role in improving glycemic control, demonstrating its rapid onset of action and its potential benefits for individuals managing diabetes.

Can you take berberine along with metformin?

Yes, but with caution and under medical supervision, as both affect blood sugar levels and could lead to hypoglycemia.

What do I need to know before taking berberine?

You should be aware of potential interactions with medications and possible side effects like gastrointestinal discomfort. For statin intolerant patients, who cannot tolerate the side effects of traditional statin therapy, berberine offers a promising natural alternative to help manage cholesterol without the adverse effects associated with statins. However, it’s crucial to consult with a healthcare provider before incorporating berberine into your regimen to navigate potential interactions and ensure it’s appropriate for your specific health situation.

What to avoid while taking berberine?

Avoid consuming alcohol and taking medications that are metabolized by the liver without consulting a healthcare provider.

What happens to your body when you take berberine?

Berberine, a natural remedy extracted from various plants, can lower blood sugar, reduce cholesterol levels, and may have antimicrobial effects. Its broad spectrum of health benefits positions berberine as a valuable addition to traditional and alternative medicine practices. It offers a holistic approach to managing health conditions, particularly for individuals looking for plant-based alternatives to conventional pharmaceuticals. The versatility of berberine in addressing multiple health concerns underscores its significance in natural health care.

What are the recommendations for berberine?

Recommendations typically include taking 500 mg two to three times a day before meals for specific health conditions.

When should you avoid berberine?

Avoid berberine if you’re pregnant, breastfeeding, or have certain health conditions without consulting a doctor. This caution is particularly important due to berberine’s potential to cross the blood-brain barrier, raising concerns about its effects on brain health and the risk of brain damage, especially in vulnerable populations such as fetuses and infants. Consulting with a healthcare provider ensures that you consider all possible risks and benefits, safeguarding against adverse outcomes, including those related to brain health.

Is berberine safe to take daily?

Yes, when taken in recommended doses, berberine is safe for daily use for a limited period. Its safety profile makes it a viable option for individuals looking to manage various health conditions. Berberine’s potential benefits in improving cholesterol levels, reducing blood sugar, and enhancing overall metabolic health can contribute to the prevention and management of coronary heart disease when used as part of a comprehensive health care plan. However, it’s important to consult with a healthcare provider to ensure its use is appropriate for your specific health needs and conditions.

Why don’t doctors recommend berberine?

Some doctors may be cautious due to the lack of long-term safety data and potential interactions with other medications. Additionally, a common side effect associated with berberine is an upset stomach, especially when taken in high doses or on an empty stomach. This potential for causing an upset stomach highlights the importance of starting with lower doses and considering timing and dietary factors when taking berberine, to minimize gastrointestinal discomfort. It is essential for individuals to discuss their health conditions and current medications with their healthcare provider to safely incorporate berberine into their regimen.

Can berberine damage kidneys?

In high doses or with long-term use, berberine could potentially harm the kidneys, though it may also have protective effects.

When is the best time to take berberine?

The best time is usually before meals to maximize its absorption and effectiveness.

Should berberine be taken at night or morning?

This can depend on personal preference and the specific health goals, but it’s often taken before meals regardless of the time of day.

How do you know if berberine is working?

Improvements in blood sugar levels, cholesterol, or weight loss can indicate that berberine is working.

What are the risks and benefits of berberine?

Benefits of using berberine include improved metabolic health, which could be particularly beneficial for individuals at risk of or managing conditions like acute coronary syndrome, as it helps in regulating blood sugar and cholesterol levels. However, risks involve potential digestive side effects, such as discomfort and diarrhea, and interactions with medications. These interactions are especially crucial to consider for those with acute coronary syndrome, who may be on a regimen of prescription drugs, underscoring the importance of consulting healthcare providers before starting berberine.

What are the benefits of berberine?

Benefits of berberine include managing diabetes, lowering cholesterol, supporting weight loss, and offering antimicrobial properties, which are particularly advantageous for individuals with an increased risk of cardiovascular diseases and infections. Its multifaceted actions help address several factors that contribute to an increased risk of chronic conditions, showcasing berberine’s potential as a versatile supplement in promoting overall health and preventing disease progression.

How many times can I take berberine?

It is commonly taken 2-3 times a day, with doses usually not exceeding 1500-2000 mg per day.

What supplements interact with berberine?

Berberine can interact with supplements that affect blood sugar levels and those metabolized by the liver.

Does berberine have negative side effects?

Possible negative side effects include gastrointestinal issues, such as diarrhea and constipation, especially at higher doses.

Is berberine better than metformin?

While berberine has shown similar effects to metformin in some studies, it is not universally considered better due to varying individual responses and lack of extensive research.

Does berberine work immediately?

Berberine begins to work soon after ingestion, but noticeable effects might take several days to weeks.

Can I take berberine 3 times a day?

Yes, taking berberine 3 times a day is common, especially with doses around 500 mg to spread its impact throughout the day.

Is berberine bad for kidneys or liver?

While generally safe, high doses or improper use of berberine could potentially stress the kidneys or liver.

Is berberine bad for your heart?

Berberine has been shown to have potential heart-protective benefits, including improving cholesterol levels and reducing blood pressure. Furthermore, animal studies suggest that berberine may also reduce cardiac damage in certain heart conditions and improve heart function, indicating its broad potential in cardiovascular health management. These findings highlight the need for further research, particularly in human clinical trials, to fully understand the extent of berberine’s heart-protective effects.

Can berberine reverse fatty liver?

Berberine has been shown to help improve liver enzymes and reduce fat accumulation in the liver in some studies, highlighting its beneficial metabolic effects on liver health. These effects are particularly important for individuals with conditions like non-alcoholic fatty liver disease (NAFLD) or metabolic syndrome, where berberine’s ability to enhance insulin sensitivity and reduce blood sugar levels contributes to its overall positive impact on metabolic health

Does berberine clean the liver?

Berberine, a compound found in plants such as tree turmeric, can support liver health by improving liver function and reducing liver fat content.

Can I drink coffee and take berberine?

Yes, but be cautious of potential interactions or enhanced effects of caffeine.

Is it OK to take berberine at night?

Taking berberine at night is generally okay and may be preferred by some for its potential blood sugar-stabilizing effects overnight. However, it is important for nursing mothers to exercise caution, as it’s not clear how berberine may affect breast milk and, consequently, the nursing infant.

How long after taking berberine can you eat?

It’s recommended to take berberine about 30 minutes before meals for optimal absorption.

How many hours does berberine last?

The effects of a single dose of berberine can last several hours, with some studies suggesting up to 8 hours.

What is the best brand of berberine to take?

The best brand will depend on quality, purity, and user reviews; looking for third-party testing can be a good indicator.

Can I take berberine instead of metformin?

While some may consider berberine as an alternative to metformin, this decision should be made with medical guidance.

What is the best way to absorb berberine?

Taking berberine with a meal or fat source can improve its absorption.

Can you take berberine while fasting?

Taking berberine while fasting is possible, but it may be more effective when taken before meals.

When should I stop taking berberine?

Consult with a healthcare provider for personalized advice, but stopping may be recommended if adverse effects occur or after a certain period of use.

How long should you take berberine?

Short-term use is generally recommended, up to a few months, due to the lack of long-term safety data.

Is berberine hard on the kidneys?

At recommended doses, berberine is not typically hard on the kidneys, but caution is advised for those with kidney disease.

Can you take berberine permanently?

Long-term continuous use is not recommended without medical supervision due to potential risks and unknown long-term effects.

Is it OK to take berberine with probiotics?

Yes, taking berberine with probiotics is generally considered safe and might even complement each other’s beneficial effects on gut health.

Does berberine raise uric acid?

There is limited evidence on berberine raising uric acid levels; consult healthcare providers for personal health concerns.

Is berberine anti-aging?

Berberine has been studied for its potential anti-aging effects, primarily through its impact on metabolic health and cell signaling pathways.

Can Type 2 diabetics take berberine?

Yes, Type 2 diabetics can take berberine as it has been shown to help lower blood sugar levels, positioning it alongside other blood sugar lowering drugs as an effective option for managing diabetes. Its ability to enhance insulin sensitivity and promote glucose metabolism makes berberine a promising addition to diabetes management strategies, especially for those seeking alternatives or complements to conventional medications.

Does berberine lower blood sugar fast?

Berberine can begin lowering blood sugar within a few days, but the full effect might take longer to be noticeable.

How long does it take for berberine to start working?

Some effects of berberine can be noticed within a few days, especially its impact on metabolic functions, but it may take weeks for the full benefits to manifest, particularly in areas such as heart disease prevention and management. Berberine’s potential to improve cardiovascular health, by reducing factors that contribute to heart disease, becomes more evident over time with consistent use. By addressing key risk factors for heart disease, such as high cholesterol and blood pressure, berberine can play a significant role in a comprehensive approach to heart health.

What are the severe side effects of berberine?

Severe side effects are rare but can include hypoglycemia, especially when taken with other blood sugar-lowering medications.

Can berberine cause damage?

While generally safe, improper use of berberine in high doses over long periods can potentially cause damage.

Does berberine affect the digestive system?

Berberine can cause gastrointestinal side effects such as diarrhea, constipation, and stomach cramps in some individuals.

Is berberine safe for liver and kidneys?

In recommended doses, berberine is generally safe for the liver and kidneys, but caution is advised for individuals with existing liver or kidney conditions.

Is berberine safe to take with a fatty liver?

Berberine has shown potential benefits for improving fatty liver disease, but it should be used under medical supervision.

How does berberine help cardiovascular health?

Is berberine safe to take with other medications?

Berberine can interact with certain medications, so it’s important to consult with a healthcare provider before combining it with other treatments.

Can berberine damage liver?

In appropriate doses, berberine is not known to damage the liver, but caution is advised for those with liver conditions.

How long does berberine stay active in your system?

The active effects of berberine can last several hours, with its half-life being around 4-8 hours.

When is the best time to take berberine and how much?

The best time to take berberine is before meals, with a common dosage being 500 mg two to three times a day.

What are the benefits of berberine for longevity?

Berberine’s potential benefits for longevity may include its effects on metabolic health, inflammation, and cellular repair mechanisms.

Is berberine a good supplement to take?

Berberine can be a beneficial supplement for certain health conditions, particularly those related to metabolic health.

What supplement is similar to berberine?

Cinnamon and alpha-lipoic acid are supplements with some similar effects to berberine, particularly in terms of blood sugar regulation.

Should berberine be taken before or after meals?

Berberine is most effective when taken before meals to enhance absorption and impact on blood sugar levels.

Why berberine is better than metformin?

Some prefer berberine to metformin due to its natural origin and broader range of health benefits, though individual responses can vary.

Can I exercise while taking berberine?

Yes, exercising while taking berberine is safe and can complement its health benefits.

How much berberine should I take with each meal?

A common dose is 500 mg before each meal, but it’s important to follow specific recommendations based on health goals and conditions.

Can berberine spike blood sugar?

Berberine is more likely to lower blood sugar levels rather than spike them, making it useful for managing diabetes.

How long do you have to take berberine to lose weight?

Weight loss effects from berberine can take several weeks to months to become noticeable, depending on diet and lifestyle factors.

Which berberine is best?

The best berberine supplement should have high purity, be third-party tested for quality, and have positive user reviews.

What cannot be taken with berberine?

Avoid taking berberine with medications that are metabolized by the liver or those that can lower blood sugar levels to prevent interactions.

Is berberine safer than metformin?

Berberine and metformin have different safety profiles; berberine is considered safe for many but lacks extensive long-term research compared to metformin.

Can you take berberine with other supplements?

Yes, but it’s important to be aware of potential interactions, especially with supplements that affect blood sugar levels.

Why is berberine bad for you?

Berberine is not inherently bad, but it can cause side effects or interact with medications, highlighting the need for cautious use.

Why can't you take berberine long term?

Long-term use of berberine is not recommended without medical supervision due to potential side effects and lack of long-term safety data.

Does berberine lower creatinine?

There is limited evidence on berberine’s effect on creatinine levels; its primary use is not for kidney function modification.

What happens if you take berberine everyday?

Taking berberine every day can lead to improvements in metabolic health, but it’s important to monitor for potential side effects.

Does berberine protect the kidneys?

Berberine may have protective effects on the kidneys by improving metabolic factors and reducing inflammation.

Reference

Yang J, Yin J, Gao H, Xu L, Wang Y, Xu L, Li M. Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients. Evid Based Complement Alternat Med. 2012;2012:363845. doi: 10.1155/2012/363845. Epub 2012 Mar 8. PMID: 22474499; PMCID: PMC3310165

Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients

This study aimed to assess the impact of berberine on preadipocytes isolated from human omental fat and on metabolic syndrome patients treated with berberine for three months. The findings demonstrated that berberine treatment led to significant inhibition of human preadipocyte differentiation, decreased leptin and adiponectin secretion, and downregulated expression of key genes associated with adipogenesis. Additionally, metabolic syndrome patients exhibited reductions in BMI, leptin levels, and HOMA-IR after three months of berberine treatment, indicating improved insulin sensitivity and adipokine profile adjustment.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310165/.
Pérez-Rubio KG, González-Ortiz M, Martínez-Abundis E, Robles-Cervantes JA, Espinel-Bermúdez MC. Effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord. 2013 Oct;11(5):366-9. doi: 10.1089/met.2012.0183. Epub 2013 Jun 28. PMID: 23808999.

Effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion

In this randomized, double-blind, placebo-controlled clinical trial involving 24 patients with metabolic syndrome, berberine administration resulted in a significant reduction in waist circumference, systolic blood pressure, triglycerides, and insulin secretion, alongside an increase in insulin sensitivity. These findings suggest that berberine may contribute to the remission of metabolic syndrome and improvements in various metabolic parameters.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/23808999/.
Och A, Och M, Nowak R, Podgórska D, Podgórski R. Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease. Molecules. 2022 Feb 17;27(4):1351. doi: 10.3390/molecules27041351. PMID: 35209140; PMCID: PMC8874997.

Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease

In recent years, the search for new solutions to improve the health of patients with metabolic syndrome has led to intensive investigation into plant nutraceuticals. Berberine, a plant alkaloid, has demonstrated scientifically supported mechanisms for 5preventing the development of atherosclerosis, type 2 diabetes, obesity, cardiovascular complications, and cancer. It positively affects fasting and postprandial blood glucose levels, glycosylated hemoglobin, and insulin resistance, while also stimulating glycolysis, improving insulin secretion, and inhibiting gluconeogenesis and adipogenesis in the liver. Additionally, berberine exhibits anti-obesity, anti-sclerotic, anti-inflammatory, neuroprotective, and antidepressive properties, and it shows promise as an adjuvant treatment in psychiatric patients by improving metabolic parameters. Berberine also acts as an anticancer agent by inducing apoptosis, cell cycle arrest, and influencing various signaling pathways related to cancer development and lipid metabolism.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874997/.
Geng FH, Li GH, Zhang X, Zhang P, Dong MQ, Zhao ZJ, Zhang Y, Dong L, Gao F. Berberine improves mesenteric artery insulin sensitivity through up-regulating insulin receptor-mediated signalling in diabetic rats. Br J Pharmacol. 2016 May;173(10):1569-79. doi: 10.1111/bph.13466. Epub 2016 Apr 5. PMID: 26914282; PMCID: PMC4842924.

Berberine improves mesenteric artery insulin sensitivity through up-regulating insulin receptor-mediated signalling in diabetic rats

Berberine, derived from Coptidis rhizome, has been shown to effectively lower blood glucose and regulate lipid metabolism. In this study, we investigated how berberine enhances vascular insulin sensitivity in diabetic rats. Berberine treatment restored impaired vasodilatation in mesenteric arteries of diabetic rats and enhanced insulin-induced vasodilatation. Mechanistically, berberine upregulated insulin receptor phosphorylation and downstream signaling molecules, including AMPK, Akt, and eNOS, indicating its potential as a preventive or adjunctive treatment for diabetic vascular complications.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842924/.
Rondanelli M, Riva A, Petrangolini G, Allegrini P, Giacosa A, Fazia T, Bernardinelli L, Gasparri C, Peroni G, Perna S. Berberine Phospholipid Is an Effective Insulin Sensitizer and Improves Metabolic and Hormonal Disorders in Women with Polycystic Ovary Syndrome: A One-Group Pretest-Post-Test Explanatory Study. Nutrients. 2021 Oct 19;13(10):3665. doi: 10.3390/nu13103665. PMID: 34684666; PMCID: PMC8538182.

Berberine Phospholipid Is an Effective Insulin Sensitizer and Improves Metabolic and Hormonal Disorders in Women with Polycystic Ovary Syndrome: A One-Group Pretest-Post-Test Explanatory Study

This study aimed to assess the effectiveness of berberine supplementation in normal-overweight PCOS women with normal menses. Berberine supplementation for 60 days resulted in significant improvements in insulin resistance, inflammation markers, lipid metabolism, sex hormone profile, symptoms related to hyperandrogenism, and body composition, without significant adverse effects on liver and kidney functions. These findings suggest that berberine could serve as a safe and beneficial dietary supplement in PCOS treatment strategies.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538182/.
Yang J, Yin J, Gao H, Xu L, Wang Y, Xu L, Li M. Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients. Evid Based Complement Alternat Med. 2012;2012:363845. doi: 10.1155/2012/363845. Epub 2012 Mar 8. PMID: 22474499; PMCID: PMC3310165.

Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients

This study aimed to explore the effects of berberine on preadipocytes from human omental fat and in metabolic syndrome patients over a 3-month period. Berberine treatment significantly inhibited preadipocyte differentiation and secretion of leptin and adiponectin, accompanied by downregulation of key mRNA expressions. In metabolic syndrome patients, berberine led to decreased BMI and leptin levels, as well as improvements in leptin/adiponectin ratio and HOMA-IR, suggesting its potential in enhancing insulin sensitivity and adjusting adipokine profiles.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310165/.
Gong M, Duan H, Wu F, Ren Y, Gong J, Xu L, Lu F, Wang D. Berberine Alleviates Insulin Resistance and Inflammation via Inhibiting the LTB4-BLT1 Axis. Front Pharmacol. 2021 Nov 4;12:722360. doi: 10.3389/fphar.2021.722360. PMID: 34803675; PMCID: PMC8599302.
Berberine Alleviates Insulin Resistance and Inflammation via Inhibiting the LTB4-BLT1 Axis

Chronic low-grade inflammation is implicated in insulin resistance, with leukotriene B4 (LTB4) exacerbating inflammation through its receptor BLT1. Berberine (BBR) has shown promise in alleviating insulin resistance via its anti-inflammatory properties, but its effects on the LTB4-BLT1 axis remain unclear. Investigating LTB4-induced inflammation in Raw264.7 and HepG2 cells, we found that BBR partially countered insulin resistance and inflammation, potentially by modulating the LTB4-BLT1 axis, suggesting a novel anti-inflammatory and anti-diabetic mechanism of BBR.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599302/.
Guo J, Chen H, Zhang X, Lou W, Zhang P, Qiu Y, Zhang C, Wang Y, Liu WJ. The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Oxid Med Cell Longev. 2021 Dec 15;2021:2074610. doi: 10.1155/2021/2074610. PMID: 34956436; PMCID: PMC8696197.

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

This systematic review and meta-analysis aimed to assess the efficacy and safety of berberine in treating patients with type 2 diabetes mellitus (T2DM). Forty-six trials were analyzed, showing significant reductions in HbA1c, FPG, and 2hPG, along with improvements in insulin resistance, lipid profiles, and inflammation factors. Berberine demonstrated clinical efficacy and safety, particularly as an adjunctive therapy, suggesting its potential as a targeted treatment for T2DM and dyslipidemia.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696197/.
Chang W, Zhang M, Li J, Meng Z, Wei S, Du H, Chen L, Hatch GM. Berberine improves insulin reiiiiiiiiiiiiiiiisistance in cardiomyocytes via activation of 5′-adenosine monophosphate-activated protein kinase. Metabolism. 2013 Aug;62(8):1159-67. doi: 10.1016/j.metabol.2013.02.007. Epub 2013 Mar 26. PMID: 23537779.

Berberine improves insulin reiiiiiiiiiiiiiiiisistance in cardiomyocytes via activation of 5′-adenosine monophosphate-activated protein kinase

This study aimed to investigate the impact of berberine (BBR) on glucose metabolism in heart cells and its potential role in regulating insulin resistance. Berberine treatment increased glucose consumption and uptake in both insulin-sensitive and insulin-resistant cardiomyocyte cells, with the effect being mediated by enhanced AMP-activated protein kinase (AMPK) activity. These findings suggest that berberine may mitigate insulin resistance in cardiomyocytes through AMPK activation, highlighting its potential therapeutic benefit in diabetic cardiomyopathy.

You can read the abstract of the article at https://www.metabolismjournal.com/article/S0026-0495(13)00054-1/abstract.
Meng Z, Yu Y, Zhang Y, Yang X, Lv X, Guan F, Hatch GM, Zhang M, Chen L. Highly bioavailable Berberine formulation improves Glucocorticoid Receptor-mediated Insulin Resistance via reduction in association of the Glucocorticoid Receptor with phosphatidylinositol-3-kinase. Int J Biol Sci. 2020 Jul 19;16(14):2527-2541. doi: 10.7150/ijbs.39508. PMID: 32792855; PMCID: PMC7415432.

Highly bioavailable Berberine formulation improves Glucocorticoid Receptor-mediated Insulin Resistance via reduction in association of the Glucocorticoid Receptor with phosphatidylinositol-3-kinase

Excessive glucocorticoid (GC) production contributes to obesity and insulin resistance via increased glucocorticoid receptor (GR) activation, yet the non-genomic effects on insulin signaling in skeletal muscle remain unclear. Berberine, known for its anti-diabetic properties, is delivered effectively via the bioavailable formulation Huang-Gui solid dispersion (HGSD). In diabetic rats, dexamethasone-treated mice, and insulin-resistant C2C12 skeletal muscle cells, HGSD treatment restored blood glucose and skeletal muscle GC levels, improved insulin signaling, and attenuated GR-mediated alterations in PI3K signaling, suggesting HGSD as a potential treatment for type 2 diabetes by mitigating GR-PI3K association in skeletal muscle.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415432/.
Dong ZH, Lin HY, Chen FL, Che XQ, Bi WK, Shi SL, Wang J, Gao L, He Z, Zhao JJ. Berberine improves intralipid-induced insulin resistance in murine. Acta Pharmacol Sin. 2021 May;42(5):735-743. doi: 10.1038/s41401-020-0493-4. Epub 2020 Aug 7. PMID: 32770172; PMCID: PMC8115075.

Berberine improves intralipid-induced insulin resistance in murine

Excessive glucocorticoid (GC) production contributes to obesity and insulin resistance via increased glucocorticoid receptor (GR) activation, yet the non-genomic effects on insulin signaling in skeletal muscle remain unclear. Berberine, known for its anti-diabetic properties, is delivered effectively via the bioavailable formulation Huang-Gui solid dispersion (HGSD). In diabetic rats, dexamethasone-treated mice, and insulin-resistant C2C12 skeletal muscle cells, HGSD treatment restored blood glucose and skeletal muscle GC levels, improved insulin signaling, and attenuated GR-mediated alterations in PI3K signaling, suggesting HGSD as a potential treatment for type 2 diabetes by mitigating GR-PI3K association in skeletal muscle.

You can read the abstract of the article at https://www.nature.com/articles/s41401-020-0493-4.
Li Y, Wang B, Shen J, Bai M, Xu E. Berberine attenuates fructose-induced insulin resistance by stimulating the hepatic LKB1/AMPK/PGC1α pathway in mice. Pharm Biol. 2020 Dec;58(1):385-392. doi: 10.1080/13880209.2020.1756349. PMID: 32393087; PMCID: PMC7269079.

Berberine attenuates fructose-induced insulin resistance by stimulating the hepatic LKB1/AMPK/PGC1α pathway in mice

In this study, the mechanism behind berberine’s ability to improve insulin sensitivity in fructose-fed mice was investigated. Berberine administration significantly reversed fructose-induced insulin resistance, as evidenced by decreased fasting insulin levels and improved oral glucose tolerance. Moreover, berberine treatment was associated with increased phosphorylation levels of key proteins involved in insulin signaling pathways, such as AKT and GSK3β, and upregulation of important metabolic regulators like PGC1α and p-AMPK. These findings suggest that berberine could be a potential therapeutic option for addressing insulin resistance.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269079/.
Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006 Aug;55(8):2256-64. doi: 10.2337/db06-0006. PMID: 16873688.

Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states

Berberine, known for its antidiabetic properties, was investigated for its metabolic effects in insulin-resistant animal models and insulin-responsive cell lines. It led to improvements in glucose tolerance, reduced body weight, and lowered plasma triglycerides in db/db mice and high-fat-fed Wistar rats. Berberine downregulated lipogenesis genes and upregulated energy expenditure-related genes in adipose tissue and muscle. Additionally, it increased AMP-activated protein kinase (AMPK) activity in adipocytes and myotubes, promoted GLUT4 translocation in myotubes independently of phosphatidylinositol 3′ kinase, and reduced lipid accumulation in adipocytes. These findings suggest that berberine’s therapeutic effects in diabetes and obesity may involve the stimulation of AMPK activity.

You can read the full article at https://diabetesjournals.org/diabetes/article/55/8/2256/12348/Berberine-a-Natural-Plant-Product-Activates-AMP.
Chen Y, Li Y, Wang Y, Wen Y, Sun C. Berberine improves free-fatty-acid-induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator-activated receptor gamma and fatty acid transferase expressions. Metabolism. 2009 Dec;58(12):1694-702. doi: 10.1016/j.metabol.2009.06.009. Epub 2009 Sep 19. PMID: 19767038.

Berberine improves free-fatty-acid-induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator-activated receptor gamma and fatty acid transferase expressions

Berberine (BBR) exhibits antidiabetic effects, yet its mechanism of action remains unclear. This study aimed to elucidate how BBR affects free-fatty-acid (FFA)-induced insulin resistance in muscle cells. Using an FFA-induced insulin-resistant model in L6 myotubes, we observed increased expressions of peroxisome proliferator-activated receptor gamma (PPARgamma) and fatty acid transferase (FAT/CD36), alongside decreased glucose consumption and insulin-mediated glucose uptake. BBR treatment improved glucose uptake in insulin-resistant cells and downregulated PPARgamma and FAT/CD36 proteins in a dose-dependent manner. These findings suggest that BBR mitigates FFA-induced insulin resistance by inhibiting fatty acid uptake, potentially through reducing PPARgamma and FAT/CD36 expressions.

You can read the abstract of the article at https://www.metabolismjournal.com/article/S0026-0495(09)00238-8/abstract.
Xing LJ, Zhang L, Liu T, Hua YQ, Zheng PY, Ji G. Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. Eur J Pharmacol. 2011 Oct 15;668(3):467-71. doi: 10.1016/j.ejphar.2011.07.036. Epub 2011 Aug 4. PMID: 21839075.

Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver

This study aimed to investigate the molecular mechanism and therapeutic effects of berberine on nonalcoholic fatty liver disease (NAFLD). Rat models were induced with NAFLD through a high-fat diet and treated with either normal saline, berberine, or pioglitazone for four weeks. Evaluation included hyperinsulinemic euglycemic clamping for insulin sensitivity, analysis of serum biochemical markers and liver triglyceride levels, and assessment of insulin receptor (IR) and insulin receptor substrate-2 (IRS-2) mRNA and protein expression. NAFLD rats exhibited insulin resistance, hepatic steatosis, and inflammation, with downregulated IRS-2 levels. Berberine treatment led to significant improvement in insulin resistance and upregulation of IRS-2 mRNA and protein levels, suggesting its potential therapeutic role in NAFLD.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0014299911008284?via%3Dihub.
Geng FH, Li GH, Zhang X, Zhang P, Dong MQ, Zhao ZJ, Zhang Y, Dong L, Gao F. Berberine improves mesenteric artery insulin sensitivity through up-regulating insulin receptor-mediated signalling in diabetic rats. Br J Pharmacol. 2016 May;173(10):1569-79. doi: 10.1111/bph.13466. Epub 2016 Apr 5. PMID: 26914282; PMCID: PMC4842924.

Berberine improves mesenteric artery insulin sensitivity through up-regulating insulin receptor-mediated signalling in diabetic rats

In this study, we investigated how berberine improves vascular insulin sensitivity in diabetic rats. Using a diabetic rat model induced by a high-fat diet and streptozotocin, we administered berberine for four weeks and assessed vascular function. Berberine treatment significantly restored impaired vasodilation in mesenteric arteries and enhanced insulin-induced vasodilation. Mechanistically, berberine upregulated phosphorylation of insulin receptor and downstream signaling molecules like AMPK, Akt, and eNOS. It also increased cell viability and autophagy in cultured endothelial cells. These results suggest that berberine improves diabetic vascular insulin sensitivity by enhancing insulin receptor-mediated signaling, highlighting its potential for preventing or treating diabetic vascular complications.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842924/.
Yi P, Lu FE, Xu LJ, Chen G, Dong H, Wang KF. Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKbeta. World J Gastroenterol. 2008 Feb 14;14(6):876-83. doi: 10.3748/wjg.14.876. PMID: 18240344; PMCID: PMC2687054.

Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKbeta

The study aimed to investigate how berberine affects insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes. The model of insulin resistance was established using palmic acid, and berberine treatment was administered concurrently. Berberine reversed the inhibition of insulin-stimulated glucose transport, reduced IKKβ Ser181 and IRS-1 Ser307 phosphorylation, and prevented nuclear translocation of NF-κB p65 protein. Although the expression of GLUT4, IKKβ, and total NF-κB p65 protein remained unchanged, berberine effectively improved insulin resistance in 3T3-L1 adipocytes induced by FFAs, highlighting its potential therapeutic role.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687054/.
Wang N, Zhang C, Xu Y, Tan HY, Chen H, Feng Y. Berberine improves insulin-induced diabetic retinopathy through exclusively suppressing Akt/mTOR-mediated HIF-1α/VEGF activation in retina endothelial cells. Int J Biol Sci. 2021 Oct 20;17(15):4316-4326. doi: 10.7150/ijbs.62868. PMID: 34803500; PMCID: PMC8579442.

Berberine improves insulin-induced diabetic retinopathy through exclusively suppressing Akt/mTOR-mediated HIF-1α/VEGF activation in retina endothelial cells

Insulin therapy is a cornerstone in managing glycemic control in diabetes, yet its efficacy in preventing diabetic retinopathy (DR) remains limited, potentially exacerbating the risk. Berberine, an isoquinoline alkaloid with notable anti-diabetic properties, is investigated here for its potential to mitigate DR progression in insulin-treated diabetes. The study explores berberine’s mechanism of action, revealing its ability to suppress insulin-induced activation of retinal endothelial cells, particularly targeting HIF-1α and VEGF through the AKT/mTOR pathway. Berberine effectively inhibited DR advancement in experimental models of both type I and type II diabetes receiving insulin therapy, underscoring its promise as an adjunctive therapy for diabetic retinopathy.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579442/.
Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008 May;57(5):712-7. doi: 10.1016/j.metabol.2008.01.013. PMID: 18442638; PMCID: PMC2410097.

Efficacy of berberine in patients with type 2 diabetes mellitus

Berberine, known for its role in regulating glucose and lipid metabolism, was evaluated for its efficacy and safety in treating type 2 diabetes mellitus (T2DM). In a pilot study, newly diagnosed T2DM patients were treated with berberine or metformin for three months, showing similar hypoglycemic effects between the two treatments. Significant improvements were observed in hemoglobin A1c, fasting and postprandial blood glucose levels, and plasma triglycerides in the berberine group. In another trial with poorly controlled T2DM patients, berberine effectively lowered fasting and postprandial blood glucose levels, reduced hemoglobin A1c, fasting plasma insulin, and insulin resistance index, as well as total and LDL cholesterol levels. Transient gastrointestinal adverse effects were reported in some patients, but no liver or kidney damage was observed. This study suggests that berberine holds promise as an oral hypoglycemic agent with favorable effects on lipid metabolism.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/.
Guo J, Chen H, Zhang X, Lou W, Zhang P, Qiu Y, Zhang C, Wang Y, Liu WJ. The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Oxid Med Cell Longev. 2021 Dec 15;2021:2074610. doi: 10.1155/2021/2074610. PMID: 34956436; PMCID: PMC8696197.

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

This systematic review and meta-analysis aimed to assess the efficacy and safety of berberine in treating type 2 diabetes mellitus (T2DM). Forty-six randomized controlled trials were analyzed, demonstrating significant reductions in glycemic parameters such as HbA1c, fasting plasma glucose, and postprandial glucose. Berberine also improved insulin resistance, lipid profiles, and inflammation markers. These findings suggest that berberine could be a valuable adjunctive therapy for T2DM, guiding its targeted clinical use and the development of medications for T2DM and dyslipidemia.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696197/.
Liang Y, Xu X, Yin M, Zhang Y, Huang L, Chen R, Ni J. Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis. Endocr J. 2019 Jan 28;66(1):51-63. doi: 10.1507/endocrj.EJ18-0109. Epub 2018 Nov 3. PMID: 30393248.

Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis

In this systematic review and meta-analysis, we assessed the impact of Berberine on glucose levels in type 2 diabetes mellitus (T2DM) patients and investigated potential modifying factors. We analyzed 28 randomized controlled trials involving 2,313 T2DM patients and found that Berberine treatment led to significant reductions in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and glycated hemoglobin (HbA1c) levels compared to control groups. Subgroup analyses revealed that the efficacy of Berberine might diminish with longer treatment durations (>90 days), higher daily dosages (>2 g/d), and older patient age (>60 years). Additionally, combining Berberine with hypoglycemic agents showed better outcomes than either treatment alone. These findings suggest that Berberine’s effectiveness could be influenced by dosage, treatment duration, and patient age.

You can read the abstract of the article at https://www.jstage.jst.go.jp/article/endocrj/66/1/66_EJ18-0109/_article.
Zhang H, Wei J, Xue R, Wu JD, Zhao W, Wang ZZ, Wang SK, Zhou ZX, Song DQ, Wang YM, Pan HN, Kong WJ, Jiang JD. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism. 2010 Feb;59(2):285-92. doi: 10.1016/j.metabol.2009.07.029. Epub 2009 Oct 1. PMID: 19800084.

Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression

Our study confirms berberine’s ability to upregulate insulin receptor (InsR) expression and improve glucose utilization in human cell lines and patients with type 2 diabetes mellitus (T2DM). Berberine increased InsR mRNA and protein expression in various human cell lines and enhanced insulin-stimulated phosphorylations of InsR beta-subunit and Akt. In clinical studies, berberine significantly reduced fasting blood glucose (FBG), hemoglobin A(1c), triglyceride, and insulin levels in T2DM patients, with efficacy comparable to metformin and rosiglitazone. Furthermore, berberine improved liver function in chronic hepatitis B and hepatitis C patients with T2DM or impaired fasting glucose. These findings suggest berberine as a promising therapy for T2DM with a mechanism distinct from traditional medications like metformin and rosiglitazone.

You can read the full article at https://www.metabolismjournal.com/article/S0026-0495(09)00316-3/abstract.
Xie W, Su F, Wang G, Peng Z, Xu Y, Zhang Y, Xu N, Hou K, Hu Z, Chen Y, Chen R. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022 Nov 16;13:1015045. doi: 10.3389/fphar.2022.1015045. PMID: 36467075; PMCID: PMC9709280.

Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis

Our meta-analysis investigated berberine’s glucose-lowering effects in type 2 diabetes mellitus (T2DM) with varying baseline fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels. Analyzing 37 studies involving 3,048 patients, we found that berberine significantly reduced FPG, HbA1c, and 2-hour plasma blood glucose (2hPBG). Subgroup analyses revealed associations between berberine’s efficacy and baseline FPG and HbA1c levels. Furthermore, berberine treatment, either alone or in combination with oral hypoglycemic agents (OHAs), did not increase the incidence of adverse events or hypoglycemia. This suggests that berberine is a safe and effective option for managing T2DM.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709280/.
Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008 May;57(5):712-7. doi: 10.1016/j.metabol.2008.01.013. PMID: 18442638; PMCID: PMC2410097.

Efficacy of berberine in patients with type 2 diabetes mellitus

Our meta-analysis investigated berberine’s glucose-lowering effects in type 2 diabetes mellitus (T2DM) with varying baseline fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels. Analyzing 37 studies involving 3,048 patients, we found that berberine significantly reduced FPG, HbA1c, and 2-hour plasma blood glucose (2hPBG). Subgroup analyses revealed associations between berberine’s efficacy and baseline FPG and HbA1c levels. Furthermore, berberine treatment, either alone or in combination with oral hypoglycemic agents (OHAs), did not increase the incidence of adverse events or hypoglycemia. This suggests that berberine is a safe and effective option for managing T2DM.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/.
Cao C, Su M. Effects of berberine on glucose-lipid metabolism, inflammatory factors and insulin resistance in patients with metabolic syndrome. Exp Ther Med. 2019 Apr;17(4):3009-3014. doi: 10.3892/etm.2019.7295. Epub 2019 Feb 22. PMID: 30936971; PMCID: PMC6434235.

Effects of berberine on glucose-lipid metabolism, inflammatory factors and insulin resistance in patients with metabolic syndrome

The study investigated the effects of berberine on glucose-lipid metabolism, inflammatory factors, and insulin resistance in patients with metabolic syndrome. Eighty patients were divided into control and observation groups, with the latter receiving berberine in addition to regular therapy. Results showed that berberine treatment significantly lowered fasting and postprandial blood glucose, insulin resistance, and blood lipid levels compared to the control group. Furthermore, levels of inflammatory markers such as hs-CRP, IL-6, and TNF-α were reduced with berberine treatment. The study suggests that berberine may effectively regulate glucose and lipid metabolism, alleviate insulin resistance, and reduce inflammation in patients with metabolic syndrome.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434235/#:~:text=The%20combined%20application%20of%20berberine,inflammatory%20response%20in%20the%20body.
Guo J, Chen H, Zhang X, Lou W, Zhang P, Qiu Y, Zhang C, Wang Y, Liu WJ. The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Oxid Med Cell Longev. 2021 Dec 15;2021:2074610. doi: 10.1155/2021/2074610. PMID: 34956436; PMCID: PMC8696197.

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The systematic review and meta-analysis assessed the efficacy and safety of berberine in treating type 2 diabetes mellitus (T2DM). Analysis of 46 trials revealed significant reductions in HbA1c, fasting plasma glucose, and postprandial glucose with berberine treatment, along with improvements in insulin resistance and lipid metabolism. Berberine also showed efficacy in reducing inflammation markers. The findings suggest that berberine, especially as an adjunctive therapy, holds promise for managing T2DM and dyslipidemia, warranting further clinical exploration and medication development.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696197/.
Dong H, Wang N, Zhao L, Lu F. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. 2012;2012:591654. doi: 10.1155/2012/591654. Epub 2012 Oct 15. PMID: 23118793; PMCID: PMC3478874.

Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis

The study aimed to evaluate the effectiveness and safety of berberine in treating type 2 diabetes mellitus (T2DM). Fourteen randomized trials involving 1068 participants were analyzed. Berberine, when combined with lifestyle modifications, demonstrated significant improvements in glycemic and lipid profiles compared to lifestyle modifications alone. However, when compared directly to oral hypoglycemic drugs, berberine showed similar glycemic control but had a mild beneficial effect on dyslipidemia. No serious adverse effects were reported. Despite these findings, caution is warranted due to the generally low methodological quality, small sample sizes, limited number of trials, and potential biases in the studies analyzed.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478874/.
Chen Y, Wang Y, Zhang J, Sun C, Lopez A. Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance. ISRN Endocrinol. 2011;2011:519371. doi: 10.5402/2011/519371. Epub 2011 Nov 20. PMID: 22363882; PMCID: PMC3262646.

Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance

The study aimed to investigate berberine’s impact on glucose homeostasis and insulin sensitivity biomarkers in male Wistar rats with streptozotocin-induced diabetes. Rats with elevated fasting blood glucose levels were divided into control and berberine-treated groups, while normal rats served as controls. After seven weeks, berberine supplementation significantly reduced fasting blood glucose levels and improved glucose tolerance. It also lowered plasma free fatty acids and C-reactive protein levels and decreased plasma triacylglycerol and cholesterol levels. Additionally, berberine inhibited dipeptidyl peptidase-4 and protein tyrosine phosphatase-1B activities, suggesting its potential in improving insulin resistance-related factors.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262646/.
Li C, He JZ, Zhou XD, Xu X. [Berberine regulates type 2 diabetes mellitus related with insulin resistance]. Zhongguo Zhong Yao Za Zhi. 2017 Jun;42(12):2254-2260. Chinese. doi: 10.19540/j.cnki.cjcmm.20170307.014. PMID: 28822177.

[Berberine regulates type 2 diabetes mellitus related with insulin resistance]

Insulin resistance (IR) denotes reduced insulin effectiveness in lowering blood sugar levels due to decreased tissue sensitivity to insulin, contributing significantly to type 2 diabetes mellitus (T2DM) development. Berberine, an extract from traditional Chinese herbs, has demonstrated safety and efficacy in lowering blood sugar, easing insulin resistance, and managing T2DM and its complications. Despite its low bioavailability, berberine’s potential in regulating intestinal flora suggests a mechanism for its blood sugar and lipid-lowering effects, highlighting the intestinal microbiota as a novel target for berberine therapy in T2DM.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/28822177/.
Leng SH, Lu FE, Xu LJ. Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion. Acta Pharmacol Sin. 2004 Apr;25(4):496-502. PMID: 15066220.

Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion

The aim of this study was to investigate the anti-diabetic effects of berberine and its impact on insulin secretion. Impaired glucose tolerance rats were treated with different doses of berberine while on a high-fat diet, and various parameters including fasting blood glucose, insulin, and lipid levels were measured. Berberine treatment significantly reduced fasting blood glucose, triglycerides, total cholesterol, free fatty acids, and apolipoprotein B levels while increasing high-density lipoprotein cholesterol and apolipoprotein AI levels. Additionally, berberine improved oral glucose tolerance. In vitro experiments demonstrated that berberine promoted insulin secretion from pancreatic cells in a dose-dependent manner. Furthermore, berberine administration in mice resulted in increased serum insulin levels and decreased blood glucose levels. Overall, these findings suggest that berberine exhibits anti-diabetic effects through its ability to stimulate insulin secretion and modulate lipid metabolism.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/15066220/.
Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, Huo L, Wang M, Hong J, Wu P, Ren G, Ning G. Treatment of type 2 diabetes and dyslipid emia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. 2008 Jul;93(7):2559-65. doi: 10.1210/jc.2007-2404. Epub 2008 Apr 8. PMID: 18397984.

Treatment of type 2 diabetes and dyslipid emia with the natural plant alkaloid berberine

Berberine, a natural plant alkaloid initially used as an antibiotic, has shown potential for lowering glucose levels, particularly noted during its use for diarrhea in diabetic patients. This study aimed to assess its efficacy and safety in treating type 2 diabetic patients with dyslipidemia. One hundred sixteen participants were randomly assigned to receive berberine or placebo for 3 months. Berberine treatment resulted in significant reductions in fasting and postload plasma glucose, HbA1c, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol compared to placebo. Glucose disposal rate also improved with berberine. Mild to moderate constipation was observed in some participants. In conclusion, berberine demonstrated effectiveness and safety in treating type 2 diabetes and dyslipidemia.

You can read the full article at https://academic.oup.com/jcem/article/93/7/2559/2598635?login=false.
Pirillo A, Catapano AL. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. Atherosclerosis. 2015 Dec;243(2):449-61. doi: 10.1016/j.atherosclerosis.2015.09.032. Epub 2015 Sep 30. PMID: 26520899.

Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies

Berberine (BBR), an isoquinoline plant alkaloid, possesses diverse pharmacological activities including antimicrobial, glucose- and cholesterol-lowering, anti-tumoral, and immunomodulatory effects. Its protective role against atherosclerosis primarily stems from its ability to lower cholesterol by increasing hepatic low-density lipoprotein receptor (LDLR) expression and reducing proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. BBR also exhibits anti-inflammatory and antioxidant properties, inhibits vascular smooth muscle cell proliferation, and improves endothelial dysfunction. Moreover, BBR enhances glucose utilization while reducing glucose absorption, leading to hypoglycemic effects. Animal studies have demonstrated BBR’s efficacy in lowering LDL-C, TC levels, and improving glucose tolerance. Clinical studies support its ability to lower cholesterol, triglycerides, and glycemia, as well as improving lipid and glucose profiles in diabetic and metabolic syndrome patients, with good tolerability. Nonetheless, further well-designed randomized controlled trials are needed to fully establish its safety and efficacy for hypercholesterolemia or diabetes treatment.

You can read the abstract of the article at https://www.atherosclerosis-journal.com/article/S0021-9150(15)30141-6/abstract.
Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab. 2008 Jan;294(1):E148-56. doi: 10.1152/ajpendo.00211.2007. Epub 2007 Oct 30. PMID: 17971514; PMCID: PMC2464622.

Berberine improves glucose metabolism through induction of glycolysis

Berberine, a botanical alkaloid renowned for its efficacy in controlling blood glucose levels in type 2 diabetes in China, has recently been found to activate AMPK, although the precise mechanism remains unclear. This study investigated berberine’s activity and mechanism of action both in vivo and in vitro. In dietary obese rats, berberine significantly enhanced insulin sensitivity after 5 weeks of administration, leading to reductions of 46% in fasting insulin and 48% in HOMA-IR. In various cell lines, berberine increased glucose consumption and uptake, independent of insulin, while also enhancing insulin-induced glucose uptake without altering IRS-1 (Ser307/312), Akt, p70 S6, and ERK phosphorylation. Berberine-induced AMPK phosphorylation persisted for >16 hours, associated with an elevation in the AMP/ATP ratio and a reduction in oxygen consumption, indicating inhibition of glucose oxidation in mitochondria. Additionally, berberine exhibited no cytotoxicity and protected the plasma membrane in L6 myotubes, suggesting its potential as a safe and effective glucose metabolism enhancer through stimulation of glycolysis.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464622/.
Liu L, Yu YL, Yang JS, Li Y, Liu YW, Liang Y, Liu XD, Xie L, Wang GJ. Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study. Naunyn Schmiedebergs Arch Pharmacol. 2010 Apr;381(4):371-81. doi: 10.1007/s00210-010-0502-0. Epub 2010 Mar 13. PMID: 20229011.

Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study

Clinical reports suggest that berberine may possess antidiabetic properties, yet the underlying mechanism remains elusive. This study aimed to investigate whether berberine exerts its hypoglycemic effects by inhibiting intestinal disaccharidases through in vivo and in vitro experiments. Diabetic rats induced by streptozotocin received oral berberine (100 or 200 mg/kg) once daily for 5 weeks, while normal rats underwent the same treatment regimen. Results showed that berberine significantly decreased disaccharidase activities and sucrase-isomaltase (SI) complex mRNA expression in both diabetic and normal rats. Moreover, berberine effectively lowered postprandial blood glucose levels induced by sucrose or maltose loading in normal rats. In cellular experiments, berberine demonstrated a concentration-dependent suppression of disaccharidase activities and downregulation of SI complex mRNA expression. Notably, only H-89, an inhibitor of protein kinase A (PKA), could reverse the decrease induced by berberine, suggesting the involvement of the PKA-dependent pathway in berberine’s inhibitory effects. Overall, berberine exhibits promising potential in mitigating disaccharidase activities and SI complex mRNA expression, offering beneficial metabolic effects in diabetic conditions.

You can read the abstract of the article at https://link.springer.com/article/10.1007/s00210-010-0502-0.
Wang Y, Yan A, Li S, Liu B, Li H, Yan Y. Efficacy and safety of berberine in the treatment of type 2 diabetes with insulin resistance: Protocol for a systematic review. Medicine (Baltimore). 2019 Aug;98(35):e16947. doi: 10.1097/MD.0000000000016947. PMID: 31464934; PMCID: PMC6736273.

Efficacy and safety of berberine in the treatment of type 2 diabetes with insulin resistance: Protocol for a systematic review

The rising incidence of diabetes mellitus (DM), particularly type 2 diabetes mellitus (T2DM) associated with insulin resistance (IR), poses significant health risks. Berberine (BBR) has shown promise in improving T2DM with IR. This study aims to assess the efficacy and safety of BBR in treating T2DM with IR through a comprehensive review of literature up to June 30, 2019. Primary outcomes include Homeostatic Model Assessment for IR (HOMA-IR), blood glucose levels, and adverse events. Data will be analyzed using software such as RevMan 5.3.5, ENDNOTE X7, and STATA 13.0, providing a valuable synthesis of evidence to guide clinical practice.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736273/.
Xia QS, Wu F, Wu WB, Dong H, Huang ZY, Xu L, Lu FE, Gong J. Berberine reduces hepatic ceramide levels to improve insulin resistance in HFD-fed mice by inhibiting HIF-2α. Biomed Pharmacother. 2022 Jun;150:112955. doi: 10.1016/j.biopha.2022.112955. Epub 2022 Apr 13. PMID: 35429745.

Berberine reduces hepatic ceramide levels to improve insulin resistance in HFD-fed mice by inhibiting HIF-2α

Numerous studies have elucidated the impact of hypoxia and ceramides on lipid and glucose metabolism, leading to insulin resistance, yet the specific roles of ceramides in hepatic hypoxia and insulin resistance remain unclear. This study investigates the correlation between hepatic hypoxia, ceramide synthesis, and insulin resistance in high-fat diet (HFD)-fed mice. Additionally, it explores the pharmacological effects of berberine on the HIF-2α-ceramide-insulin resistance pathway, based on molecular docking interactions. Results indicate that berberine mitigates hypoxia-induced ceramide production and alleviates ceramide-induced insulin resistance, shedding light on potential therapeutic avenues for type 2 diabetes mellitus (T2DM).

You can read the full article at https://www.sciencedirect.com/science/article/pii/S0753332222003444?via%3Dihub.
Tian CM, Jiang X, Ouyang XX, Zhang YO, Xie WD. Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice. Chin J Nat Med. 2016 Jul;14(7):518-26. doi: 10.1016/S1875-5364(16)30061-9. PMID: 27507202.

Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice

The study aimed to assess whether combining berberine with canagliflozin could enhance antidiabetic effects and mitigate adverse effects in diabetes mellitus. Using streptozotocin-induced diabetic mice, researchers investigated their combined impact on glucose metabolism and kidney function. Results revealed that the combination (BC) significantly lowered fasting and postprandial blood glucose levels, diet, and water intake compared to berberine or canagliflozin alone. Notably, BC demonstrated greater reductions in blood urea nitrogen and creatinine levels, along with decreased urine glucose excretion compared to canagliflozin alone. Additionally, BC increased phosphorylated 5′ AMP-activated protein kinase (pAMPK) expression and decreased tumor necrosis factor alpha (TNFα) levels in kidneys. These findings suggest that BC offers stronger antidiabetic effects with fewer kidney-related side effects, likely mediated by synergistic promotion of pAMPK expression and reduction of TNFα levels. This study highlights the potential of combining canagliflozin with berberine as a promising treatment for diabetes mellitus, warranting further investigation into its underlying mechanisms.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S1875536416300619?via%3Dihub.
Pirillo A, Catapano AL. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. Atherosclerosis. 2015 Dec;243(2):449-61. doi: 10.1016/j.atherosclerosis.2015.09.032. Epub 2015 Sep 30. PMID: 26520899.

Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies

Berberine (BBR), an isoquinoline plant alkaloid, exhibits diverse pharmacological activities such as antimicrobial, glucose- and cholesterol-lowering, anti-tumoral, and immunomodulatory effects. Its protective role in atherosclerosis primarily stems from cholesterol reduction, achieved by increasing hepatic low-density lipoprotein receptor (LDLR) expression and decreasing proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. BBR also demonstrates anti-inflammatory and antioxidant properties, inhibits vascular smooth muscle cell proliferation, and improves endothelial dysfunction. Moreover, it enhances glucose utilization in adipocytes and myocytes while decreasing glucose absorption in intestinal cells, resulting in hypoglycemic effects. Animal studies show BBR reduces LDL-C and total cholesterol levels in hypercholesterolemic models, and improves glucose tolerance and reduces adipose tissue mass in diabetic models. Clinical studies suggest BBR effectively lowers cholesterol, triglycerides, and LDL-C, increases HDL-C, and improves glycemic control and metabolic profile in diabetic and metabolic syndrome patients. These findings support BBR as a potential therapeutic option for hypercholesterolemia and diabetes, warranting further well-designed randomized controlled trials to confirm safety and efficacy.

You can read the full article at https://www.atherosclerosis-journal.com/article/S0021-9150(15)30141-6/abstract.
Zhang R, Xiao Y, Yan J, Yang W, Wu X, Mei Z, Zhou Z. Effects of Berberine Plus Inulin on Diabetes Care in Patients With Latent Autoimmune Diabetes in Adults: Protocol for a Randomized Controlled Trial. Front Endocrinol (Lausanne). 2022 Jun 15;13:876657. doi: 10.3389/fendo.2022.876657. PMID: 35784546; PMCID: PMC9241519.

Effects of Berberine Plus Inulin on Diabetes Care in Patients With Latent Autoimmune Diabetes in Adults: Protocol for a Randomized Controlled Trial

In this study, the combined effects of oral berberine (BBR) and inulin with insulin therapy were assessed in patients with latent autoimmune diabetes in adults (LADA), a multifaceted form of diabetes characterized by autoimmune β-cell destruction and insulin resistance. Berberine, known for its antidiabetic, anti-inflammatory, and antibacterial properties, and inulin, a prebiotic with demonstrated benefits in glycemic control and inflammation modulation, were investigated for their potential synergistic effects on diabetes management in LADA patients undergoing insulin therapy.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241519/.
Ma YG, Liang L, Zhang YB, Wang BF, Bai YG, Dai ZJ, Xie MJ, Wang ZW. Berberine reduced blood pressure and improved vasodilation in diabetic rats. J Mol Endocrinol. 2017 Oct;59(3):191-204. doi: 10.1530/JME-17-0014. Epub 2017 May 17. PMID: 28515053.

Berberine reduced blood pressure and improved vasodilation in diabetic rats

In this study, the effects of berberine on blood pressure reduction and vascular protection in diabetic rats were investigated. Berberine was administered intragastrically at varying dosages to diabetic rats for 8 weeks, following streptozotocin injection. The results showed that chronic administration of 100 mg/kg/day of berberine not only lowered blood glucose levels but also reduced blood pressure and improved vasodilation in diabetic rats. Furthermore, berberine enhanced the function and expression of the BKCa β1-subunit in cerebral vascular smooth muscle cells, suggesting its potential as a dual therapy for managing hyperglycemia and hypertension in diabetes. These findings highlight the role of BKCa channel activation as a mechanism underlying berberine’s vascular protective effects in diabetes.

You can read the full article at https://jme.bioscientifica.com/view/journals/jme/59/3/JME-17-0014.xml.
Chueh WH, Lin JY. Protective effect of berberine on serum glucose levels in non-obese diabetic mice. Int Immunopharmacol. 2012 Mar;12(3):534-8. doi: 10.1016/j.intimp.2012.01.003. Epub 2012 Jan 18. PMID: 22266065.

Protective effect of berberine on serum glucose levels in non-obese diabetic mice

In this study, the effects of berberine on serum glucose levels in type 1 diabetes (T1D) were investigated using non-obese diabetic (NOD) mice. The mice were divided into groups receiving different doses of berberine for 14 weeks, while changes in body weight, oral glucose challenge, and serum glucose levels were monitored. Berberine supplementation led to a dose-dependent decrease in fasting serum glucose levels in NOD mice, approaching levels seen in normal mice, without causing toxic side effects. Additionally, a negative and non-linear correlation was observed between serum berberine levels and fasting glucose levels in the treated mice. These findings highlight the potential of berberine as a therapeutic agent for managing hyperglycemia in T1D.

You can read the abstract of the article at https://www.sciencedirect.com/science/article/abs/pii/S1567576912000124?via%3Dihub.
Shan YQ, Ren G, Wang YX, Pang J, Zhao ZY, Yao J, You XF, Si SY, Song DQ, Kong WJ, Jiang JD. Berberine analogue IMB-Y53 improves glucose-lowering efficacy by averting cellular efflux especially P-glycoprotein efflux. Metabolism. 2013 Mar;62(3):446-56. doi: 10.1016/j.metabol.2012.09.009. Epub 2012 Oct 15. PMID: 23079743.

Berberine analogue IMB-Y53 improves glucose-lowering efficacy by averting cellular efflux especially P-glycoprotein efflux

This study aimed to address the issue of cellular efflux, particularly by P-glycoprotein (P-gp), which reduces the bioavailability of berberine (BBR). Through molecular docking, pseudo-berberine (IMB-Y53) was identified as having low affinity to P-gp. IMB-Y53 exhibited prolonged retention in various cell types compared to BBR, and P-gp inhibitor tetrandrine had no effect on IMB-Y53 efflux. In rats, IMB-Y53 demonstrated improved bioavailability compared to BBR, leading to enhanced glucose-lowering efficacy in diabetic mice. These findings underscore the potential of targeting cellular efflux mechanisms to enhance the therapeutic benefits of BBR.

You can read the abstract of the article at https://www.metabolismjournal.com/article/S0026-0495(12)00348-4/abstract.
Dong H, Wang N, Zhao L, Lu F. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. 2012;2012:591654. doi: 10.1155/2012/591654. Epub 2012 Oct 15. PMID: 23118793; PMCID: PMC3478874.

Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis

The objective of this study was to evaluate the effectiveness and safety of berberine in treating type 2 diabetes mellitus (T2DM). Fourteen randomized trials involving 1068 participants were analyzed, revealing that berberine, when combined with lifestyle modification, demonstrated significant hypoglycemic and antidyslipidemic effects compared to lifestyle modification alone or with placebo. While berberine did not show superior glycemic control compared to certain oral hypoglycemic drugs like metformin or glipizide, it exhibited a mild antidyslipidemic effect. However, caution is warranted due to the generally low methodological quality, small sample sizes, and limited number of trials, emphasizing the need for further research to fully understand berberine’s efficacy and safety profile in T2DM treatment.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478874/.
Ilyas Z, Perna S, Al-Thawadi S, Alalwan TA, Riva A, Petrangolini G, Gasparri C, Infantino V, Peroni G, Rondanelli M. The effect of Berberine on weight loss in order to prevent obesity: A systematic review. Biomed Pharmacother. 2020 Jul;127:110137. doi: 10.1016/j.biopha.2020.110137. Epub 2020 Apr 27. PMID: 32353823.

The effect of Berberine on weight loss in order to prevent obesity: A systematic review

This study offers a comprehensive examination of Berberine’s efficacy in managing obesity and its metabolic consequences, drawing from experimental studies conducted in vitro, in animals, and in humans. Summarizing various effects and mechanisms, Berberine has shown to influence gut microbiota, inhibit glucose-related pathways, decrease adipocyte differentiation, and modulate lipid levels. These effects are observed across different dosages, with Berberine demonstrating promising results in both preclinical and human studies. The review underscores Berberine’s potential as a therapeutic agent for obesity treatment and prevention.

You can read the full article at https://www.sciencedirect.com/science/article/pii/S0753332220303292?via%3Dihub.
Zhang W, Xu YC, Guo FJ, Meng Y, Li ML. Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus. Chin Med J (Engl). 2008 Nov 5;121(21):2124-8. PMID: 19080170.

Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus

This study aimed to assess the anti-diabetic effects of cinnamaldehyde (Cin), berberine (Ber), and metformin (Met) in rat models of type 2 diabetes mellitus (T2DM) and their impact on the RBP4-GLUT4 system. After four weeks of treatment, both Cin and Ber demonstrated significant hypolipidemic, hypoglycemic, and insulin-sensitizing effects, outperforming Met in some aspects. They notably lowered serum RBP4 levels and increased tissue GLUT4 protein expression, with Cin showing particularly promising results. These findings suggest that Cin and Ber hold potential as effective treatments for T2DM, operating through modulation of the RBP4-GLUT4 system.

You can read the full article at https://journals.lww.com/cmj/fulltext/2008/11010/anti_diabetic_effects_of_cinnamaldehyde_and.3.aspx.
Yao Y, Zuo J, Chen L, Wei Y. Combination of metformin and berberine represses the apoptosis of sebocytes in high-fat diet-induced diabetic hamsters and an insulin-treated human cell line. Cell Biochem Funct. 2020 Jul;38(5):567-573. doi: 10.1002/cbf.3504. Epub 2020 Feb 20. PMID: 32080865.

Combination of metformin and berberine represses the apoptosis of sebocytes in high-fat diet-induced diabetic hamsters and an insulin-treated human cell line

In this study, the combined treatment of berberine and metformin was investigated for its effects on sebocyte apoptosis in high-fat diet-induced diabetic hamsters and insulin-treated human cell lines. The treatment resulted in reduced body weight, liver fat accumulation, and insulin and glucose concentrations in hamsters. Glucose tolerance was also improved in hamsters receiving berberine. Moreover, berberine and metformin attenuated cell death rates in sebocytes, potentially through the Bik pathway. These findings suggest that berberine may offer therapeutic benefits for managing insulin-related sebaceous gland diseases, such as acne, by mitigating cell apoptosis and improving metabolic parameters in diabetic conditions.

You can read the abstract of the article at https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/cbf.3504.
Wu YS, Li ZM, Chen YT, Dai SJ, Zhou XJ, Yang YX, Lou JS, Ji LT, Bao YT, Xuan L, Lin LN, Li CY. Berberine Improves Inflammatory Responses of Diabetes Mellitus in Zucker Diabetic Fatty Rats and Insulin-Resistant HepG2 Cells through the PPM1B Pathway. J Immunol Res. 2020 Aug 18;2020:2141508. doi: 10.1155/2020/2141508. PMID: 32908938; PMCID: PMC7450322.

Berberine Improves Inflammatory Responses of Diabetes Mellitus in Zucker Diabetic Fatty Rats and Insulin-Resistant HepG2 Cells through the PPM1B Pathway

This study investigates the impact of berberine (BBR) and protein phosphatase, Mg2+/Mn2+-dependent 1B (PPM1B) on insulin resistance (IR) using ZDF rats and HepG2-IR cells. BBR treatment significantly reduced body weight, blood glucose levels, and liver pathology in ZDF rats with upregulated PPM1B. In HepG2-IR cells, BBR improved glucose consumption, uptake, and inflammation. Knockdown of PPM1B exacerbated inflammation and glycometabolism disorder in HepG2-IR cells. Mechanistically, BBR modulated the expression of cAMP, PKA, PPM1B, PPARγ, LRP1, GLUT4, NF-κB p65, JNK, pIKKβ Ser181, IKKβ, IRS-1 Ser307, IRS-1, IRS-2 Ser731, IRS-2, PI3K p85, and AKT Ser473, suggesting its potential in regulating IR progression through liver-related pathways.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450322/.
Lu Y, Zhang X, He J, Dai Z, Shi P, Lu Y, Chang F. The effects of berberine on inflammatory markers in Chinese patients with metabolic syndrome and related disorders: a meta-analysis of randomized controlled trials. Inflammopharmacology. 2022 Jun;30(3):1063-1077. doi: 10.1007/s10787-022-00976-2. Epub 2022 Mar 29. PMID: 35352233; PMCID: PMC9135894.

The effects of berberine on inflammatory markers in Chinese patients with metabolic syndrome and related disorders: a meta-analysis of randomized controlled trials

In this meta-analysis of randomized controlled trials, berberine’s effects on inflammatory markers in metabolic syndrome (MetS) and related disorders were systematically evaluated. Among 52 included studies involving 4616 patients, berberine significantly reduced levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) but had no significant effect on interleukin 1β (IL-1β). These findings suggest a potential role for berberine in decreasing inflammation in MetS and related conditions, though further large-scale investigations are warranted to confirm its efficacy.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135894/.
Xie W, Su F, Wang G, Peng Z, Xu Y, Zhang Y, Xu N, Hou K, Hu Z, Chen Y, Chen R. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022 Nov 16;13:1015045. doi: 10.3389/fphar.2022.1015045. PMID: 36467075; PMCID: PMC9709280.

Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis

In recent years, berberine has emerged as a potential insulin secretagogue for type 2 diabetes, offering a safer alternative to traditional agents like sulfonylureas and glinides due to its reduced risk of hypoglycemia. To evaluate its glucose-lowering effects across varying baseline fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels, we conducted a meta-analysis of randomized controlled trials involving 3,048 patients. Berberine demonstrated significant reductions in FPG, HbA1c, and 2-hour plasma blood glucose (2hPBG), with effects varying based on baseline FPG and HbA1c levels. Importantly, berberine treatment did not increase the risk of total adverse events or hypoglycemia, whether used alone or in combination with oral hypoglycemic agents (OHAs). These findings underscore the potential of berberine as a safe and effective treatment option for type 2 diabetes.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709280/.
Zhang H, Wei J, Xue R, Wu JD, Zhao W, Wang ZZ, Wang SK, Zhou ZX, Song DQ, Wang YM, Pan HN, Kong WJ, Jiang JD. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism. 2010 Feb;59(2):285-92. doi: 10.1016/j.metabol.2009.07.029. Epub 2009 Oct 1. PMID: 19800084.

Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression

In our investigation, we explored the insulin receptor (InsR)-up-regulating and glucose-lowering effects of berberine (BBR) in humans, building upon our previous findings in vitro and in animal models. We observed that BBR increased InsR mRNA and protein expression across various human cell lines, enhancing insulin-stimulated phosphorylations of InsR beta-subunit and Akt. In a clinical study involving patients with type 2 diabetes mellitus (T2DM), BBR significantly reduced fasting blood glucose (FBG), hemoglobin A(1c), triglyceride, and insulin levels, with efficacy comparable to metformin and rosiglitazone. Moreover, BBR treatment elevated the percentages of peripheral blood lymphocytes expressing InsR in T2DM patients and effectively lowered FBG in individuals with chronic hepatitis B and hepatitis C. These findings underscore BBR’s potential as a therapeutic agent for T2DM, offering a distinct mechanism of action compared to conventional medications like metformin and rosiglitazone.

You can read the abstract of the article at https://www.metabolismjournal.com/article/S0026-0495(09)00316-3/abstract.
Xie W, Su F, Wang G, Peng Z, Xu Y, Zhang Y, Xu N, Hou K, Hu Z, Chen Y, Chen R. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022 Nov 16;13:1015045. doi: 10.3389/fphar.2022.1015045. PMID: 36467075; PMCID: PMC9709280.

Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis

In recent years, berberine has emerged as a potential treatment for type 2 diabetes due to its ability to promote insulin secretion without causing hypoglycemia. To investigate its glucose-lowering effects across different baseline fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels, we conducted a meta-analysis of randomized controlled trials. Our analysis, which included 37 studies involving 3,048 patients, revealed that berberine significantly reduced FPG, HbA1c, and 2-hour plasma blood glucose levels. Subgroup analyses indicated that the efficacy of berberine was associated with baseline FPG and HbA1c levels in type 2 diabetes. Furthermore, berberine treatment, either alone or in combination with oral hypoglycemic agents, did not increase the risk of adverse events or hypoglycemia. These findings suggest that berberine holds promise as a safe and effective therapeutic option for managing type 2 diabetes.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709280/.
Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006 Aug;55(8):2256-64. doi: 10.2337/db06-0006. PMID: 16873688.

Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states

Berberine’s metabolic effects were investigated in insulin-resistant animal models and cell lines, revealing its potential as an antidiabetic agent. In db/db mice, berberine improved glucose tolerance and reduced body weight without affecting food intake. Similarly, in high-fat-fed Wistar rats, berberine improved insulin action, reduced body weight, and lowered plasma triglycerides. Berberine also downregulated lipogenesis-related genes and upregulated energy expenditure-related genes in adipose tissue and muscle. In cell studies, berberine increased AMP-activated protein kinase (AMPK) activity, promoted GLUT4 translocation, and reduced lipid accumulation, suggesting its beneficial effects in diabetes and obesity treatment, possibly mediated through AMPK stimulation.

You can read the full article at https://diabetesjournals.org/diabetes/article/55/8/2256/12348/Berberine-a-Natural-Plant-Product-Activates-AMP.
Zhang Q, Xiao X, Feng K, Wang T, Li W, Yuan T, Sun X, Sun Q, Xiang H, Wang H. Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism. Evid Based Complement Alternat Med. 2011;2011:924851. doi: 10.1155/2011/924851. Epub 2010 Sep 26. PMID: 20953398; PMCID: PMC2952334.

Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

Berberine’s impact on glucose and lipid metabolism was investigated in KKAy mice to elucidate its mechanism. Mice were divided into berberine and control groups, with measurements including fasting blood glucose, weight, lipid profile, and serum insulin. Berberine significantly reduced fasting blood glucose, insulin resistance, cholesterol, and triglycerides compared to controls. Gene expression analysis revealed upregulation of GLUT4, MAPK14, MAPK8, PPARα, UCP2, and HNF4α, while downregulating PPARγ, CEBP, PGC 1α, and resistin. These findings suggest berberine’s multifaceted regulation of glucose and lipid metabolism through pathways involving AMPK, p38 MAPK, GLUT4, JNK, and PPARα.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952334/.
Xia X, Yan J, Shen Y, Tang K, Yin J, Zhang Y, Yang D, Liang H, Ye J, Weng J. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS One. 2011 Feb 3;6(2):e16556. doi: 10.1371/journal.pone.0016556. PMID: 21304897; PMCID: PMC3033390.

Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis

Berberine (BBR), derived from the Chinese herb Huanglian (Coptis chinensis French), enhances glucose metabolism in type 2 diabetes via AMPK activation and insulin sensitivity improvement. This study investigates BBR’s effects on diabetic rats induced by a high-fat diet. BBR significantly reduces fasting glucose levels and downregulates gluconeogenic genes (PEPCK and G6Pase) in the liver, while also decreasing hepatic steatosis and inhibiting FAS expression. Transcription factors FoxO1, SREBP1c, and ChREBP activities are reduced, and insulin signaling remains unaffected. In hepatocytes, BBR inhibits oxygen consumption and lowers ATP levels, indicating direct inhibition of gluconeogenesis possibly through mitochondrial inhibition. These findings support BBR’s insulin-independent pathway in improving glucose metabolism.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033390/.
Zhang B, Pan Y, Xu L, Tang D, Dorfman RG, Zhou Q, Yin Y, Li Y, Zhou L, Zhao S, Zou X, Wang L, Zhang M. Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting deacetylase SIRT3. Endocrine. 2018 Dec;62(3):576-587. doi: 10.1007/s12020-018-1689-y. Epub 2018 Aug 16. PMID: 30117113.

Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting deacetylase SIRT3

Numerous studies have highlighted berberine’s efficacy in lowering glucose levels in type 2 diabetes patients, primarily attributed to improved insulin sensitivity. However, its precise hypoglycemic mechanism remains unclear. Here, we unveil a novel mechanism whereby berberine antagonizes glucagon signaling and implicates SIRT3 in its hypoglycemic effect. By inhibiting deacetylase SIRT3, berberine induces mitochondrial dysfunction and AMP accumulation. This, in turn, activates the AMPK signaling pathway, enhancing glucose uptake while diminishing cyclic AMP (cAMP) levels, thus inhibiting critical protein targets of PKA. Notably, berberine’s glucagon inhibition stabilizes PEPCK1, a key gluconeogenesis enzyme, through ubiquitination and degradation, alongside increased PEPCK1 acetylation. Remarkably, this glucagon antagonism by berberine operates independently of AMPK activation. These findings underscore berberine’s potential in modulating glucose metabolism through SIRT3 inhibition, offering insights for antidiabetic drug development.

You can read the abstract of the article at https://link.springer.com/article/10.1007/s12020-018-1689-y.
Kong WJ, Zhang H, Song DQ, Xue R, Zhao W, Wei J, Wang YM, Shan N, Zhou ZX, Yang P, You XF, Li ZR, Si SY, Zhao LX, Pan HN, Jiang JD. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism. 2009 Jan;58(1):109-19. doi: 10.1016/j.metabol.2008.08.013. PMID: 19059538.

Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression

Berberine (BBR), a natural product with hypoglycemic and insulin-sensitizing properties, lacks a fully elucidated mechanism. This study aims to unravel its molecular action against insulin resistance. We identify the insulin receptor (InsR) as a BBR target to enhance insulin sensitivity. BBR boosts InsR mRNA and protein expression in cultured human liver cells and L6 rat skeletal muscle cells in a dose- and time-dependent manner, consequently improving glucose consumption in the presence of insulin. Silencing InsR or inhibiting phosphoinositide 3-kinase abolishes this effect, indicating InsR’s pivotal role. BBR activates InsR gene expression via a protein kinase C (PKC)-dependent pathway, evidenced by InsR promoter activation and mRNA transcription. In type 2 diabetes mellitus rats, BBR treatment lowers fasting blood glucose and serum insulin levels, enhances insulin sensitivity, and upregulates InsR mRNA alongside hepatic PKC activity. Furthermore, BBR reduces blood glucose in type 2 diabetes mellitus mice but not in insulin-deficient type 1 diabetes mellitus mice. These findings underscore BBR’s unique efficacy against insulin resistance in type 2 diabetes mellitus and metabolic syndrome.

You can read the full article at https://www.metabolismjournal.com/article/S0026-0495(08)00327-2/fulltext.
Xia Y, Yang HC, Zhang K, Tian JJ, Li ZF, Yu EM, Li HY, Gong WB, Xie WP, Wang GJ, Xie J. Berberine regulates glucose metabolism in largemouth bass by modulating intestinal microbiota. Front Physiol. 2023 Mar 9;14:1147001. doi: 10.3389/fphys.2023.1147001. PMID: 36969581; PMCID: PMC10033662.

Berberine regulates glucose metabolism in largemouth bass by modulating intestinal microbiota

This study investigated the impact of intestinal microbiota on berberine (BBR)-mediated glucose metabolism regulation in largemouth bass. Largemouth bass were fed with control diet, BBR-supplemented diet, antibiotic (ATB)-supplemented diet, and BBR + ATB-supplemented diet. BBR improved growth, decreased hepatosomatic and visceral weight indices, and modulated serum cholesterol, glucose, and bile acid levels. ATB treatment altered these parameters adversely, while BBR + ATB co-treatment showed intermediate effects. High-throughput sequencing revealed microbiota alterations, with BBR increasing the number of culturable bacteria and promoting Enterobacter cloacae growth, which metabolizes carbohydrates. BBR mitigated hepatocyte vacuolation and lipid distribution in liver tissue, indicating improved glucose metabolism. This suggests that BBR regulates glucose metabolism in largemouth bass by modulating intestinal microbiota.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10033662/.
Chen Y, Li Q, Zhao S, Sun L, Yin Z, Wang X, Li X, Iwakiri Y, Han J, Duan Y. Berberine protects mice against type 2 diabetes by promoting PPARγ-FGF21-GLUT2-regulated insulin sensitivity and glucose/lipid homeostasis. Biochem Pharmacol. 2023 Dec;218:115928. doi: 10.1016/j.bcp.2023.115928. Epub 2023 Nov 17. PMID: 37979703.

Berberine protects mice against type 2 diabetes by promoting PPARγ-FGF21-GLUT2-regulated insulin sensitivity and glucose/lipid homeostasis

Type 2 diabetes (T2D) presents significant challenges due to insulin sensitivity issues and disrupted glucose/lipid balance. Berberine (BBR) offers therapeutic benefits in T2D by regulating these metabolic aspects and enhancing insulin sensitivity and energy expenditure. While the role of BBR in fibroblast growth factor 21 (FGF21) function has been noted, its precise mechanism in T2D remains unclear. Through studies involving T2D mouse models and human liver carcinoma cells, we found that BBR activates FGF21 expression via upregulating peroxisome proliferator-activated receptor γ (PPARγ). BBR mitigates glucosamine hydrochloride-induced insulin resistance and enhances glucose transporter 2 (GLUT2) expression in a PPARγ/FGF21-dependent manner. In T2D mice, BBR elevates PPARγ, FGF21, and GLUT2 expression in the liver and GLUT2 in the pancreas, reversing insulin resistance and liver lipid accumulation. However, these effects are diminished in FGF21-deficient mice. This study underscores the therapeutic potential of BBR in T2D via the PPARγ-FGF21-GLUT2 pathway, offering insights into its mechanism of action.

You can read the full article at https://www.sciencedirect.com/science/article/pii/S000629522300521X?via%3Dihub.
Deng XW, Xie N. [Progress of berberine for treatment of type 2 diabetes]. Zhongguo Zhong Yao Za Zhi. 2014 Apr;39(8):1374-8. Chinese. PMID: 25039167.

[Progress of berberine for treatment of type 2 diabetes]

Berberine, the primary component of Coptidis Rhizoma, has long been recognized for its anti-infective and anti-inflammatory properties in gastrointestinal ailments. Recent research has unveiled its potential in regulating glucose and lipid metabolism, supported by clinical trials and animal studies. Berberine’s mechanisms in diabetes encompass enhancing beta-cell function, stimulating insulin secretion and islet regeneration, reducing lipid levels, and modulating transcription factors such as PPARgamma, C/EBPalpha, and SREBP-1c. Additionally, it exhibits antioxidant properties and inhibits reductase to counteract oxidative stress and regulate metabolic signaling pathways. While evidence from clinical trials and animal models suggests its efficacy in improving insulin resistance, further large-scale, multicenter trials are warranted to comprehensively assess its impact on diabetes and its complications within the framework of evidence-based medicine.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/25039167/.
Pang B, Zhao LH, Zhou Q, Zhao TY, Wang H, Gu CJ, Tong XL. Application of berberine on treating type 2 diabetes mellitus. Int J Endocrinol. 2015;2015:905749. doi: 10.1155/2015/905749. Epub 2015 Mar 11. PMID: 25861268; PMCID: PMC4377488.

Application of berberine on treating type 2 diabetes mellitus

Traditional Chinese medicine (TCM) presents promising prospects in the management of diabetes mellitus (DM), offering advantages of reduced toxicity and side effects compared to conventional treatments. Berberine (BBR), a renowned natural remedy, exhibits diverse pharmacological effects in glucose metabolism, including enhancing insulin sensitivity, insulin secretion, and glycolysis, while inhibiting gluconeogenesis and modulating gut microbiota. Its antioxidant and anti-inflammatory properties make it effective in treating diabetic complications such as nephropathy, neuropathy, and cardiomyopathy. Clinical trials support BBR’s efficacy and safety, with considerations for dosage, formulation, and potential side effects discussed alongside traditional Chinese medical principles. This review integrates scientific evidence and clinical experience to guide clinicians in the appropriate and rational use of BBR for diabetic patients.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377488/.
Xia X, Yan J, Shen Y, Tang K, Yin J, Zhang Y, Yang D, Liang H, Ye J, Weng J. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS One. 2011 Feb 3;6(2):e16556. doi: 10.1371/journal.pone.0016556. PMID: 21304897; PMCID: PMC3033390.

Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis

Berberine (BBR), derived from the Chinese herb Huanglian (Coptis chinensis French), is known to enhance glucose metabolism in type 2 diabetic patients through mechanisms involving the activation of adenosine monophosphate activated protein kinase (AMPK) and improved insulin sensitivity. However, its exact mechanisms for reducing blood glucose remain unclear. This study investigates the liver response to BBR in diabetic rats induced by a high-fat diet. BBR significantly decreased fasting glucose levels and reduced gluconeogenic gene expression, such as Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), while also mitigating hepatic steatosis and inhibiting fatty acid synthase (FAS) expression. Furthermore, BBR decreased the activities of transcription factors like Forkhead transcription factor O1 (FoxO1), sterol regulatory element-binding protein 1c (SREBP1), and carbohydrate responsive element-binding protein (ChREBP). Interestingly, BBR did not alter the insulin signaling pathway in the liver but rather inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP) levels in cultured hepatocytes, suggesting a direct inhibition of gluconeogenesis in the liver through mitochondria inhibition, thus highlighting an insulin-independent pathway for BBR’s improvement of glucose metabolism.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033390/.
Zhang Q, Xiao X, Li M, Li W, Yu M, Zhang H, Ping F, Wang Z, Zheng J. Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine. BMC Complement Altern Med. 2014 Jun 9;14:188. doi: 10.1186/1472-6882-14-188. PMID: 24912407; PMCID: PMC4057525.

Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine

Berberine is known for its ability to improve glucose and lipid metabolism disorders, yet its limited absorption into the bloodstream from the gut has left its underlying mechanism elusive. In this study, we investigated berberine’s effect on glucose metabolism in diabetic rats, hypothesizing that it acts directly in the terminal ileums. Our findings revealed that 8 weeks of berberine treatment significantly reduced fasting blood glucose levels and improved oral glucose tolerance. Notably, plasma postprandial glucagon-like peptide-1 (GLP-1) levels were elevated in berberine-treated groups. Transcriptomic analysis of the ileum identified significant changes in gene expression, particularly in pathways related to MAPK signaling and GnRH-Glp-1. This was corroborated by up-regulation of Glp1r and Mapk10 and down-regulation of Gnrhr and Gnrh1 in the berberine-treated group. These results suggest that berberine may modulate blood glucose levels through the MAPK and GnRH-Glp-1 pathways in the ileum of diabetic rats.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057525/.
Tavaf MJ, Soltanmohammadi A, Zargarani S, Yazdanpanah E, Sadighimoghaddam B, Yousefi B, Sameni HR, Haghmorad D. Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells. Immun Inflamm Dis. 2023 Jan;11(1):e766. doi: 10.1002/iid3.766. PMID: 36705421; PMCID: PMC9837936.

Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells

In this study, the effects of berberine on experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, were investigated in female C57BL/6 mice. Berberine administration at low and high doses significantly reduced clinical scores compared to the control group, showing lower lymphocyte infiltration and demyelination in the CNS. Treatment with berberine also decreased pro-inflammatory cytokines while increasing anti-inflammatory cytokine expression, suggesting its potential as a protective agent in EAE by enhancing Treg and Th2 cell function alongside its anti-inflammatory properties.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837936/.
Tang M, Yuan D, Liao P. Berberine improves intestinal barrier function and reduces inflammation, immunosuppression, and oxidative stress by regulating the NF-κB/MAPK signaling pathway in deoxynivalenol-challenged piglets. Environ Pollut. 2021 Nov 15;289:117865. doi: 10.1016/j.envpol.2021.117865. Epub 2021 Jul 31. PMID: 34358871.

Berberine improves intestinal barrier function and reduces inflammation, immunosuppression, and oxidative stress by regulating the NF-κB/MAPK signaling pathway in deoxynivalenol-challenged piglets

This study aimed to assess the impact of berberine (BBR) on the intestinal health of piglets exposed to deoxynivalenol (DON). Piglets were divided into three groups: basal diet, basal diet with DON, and basal diet with DON and BBR. Results showed that BBR improved growth performance and inhibited DON-induced intestinal injury by enhancing antioxidant enzyme expression, T cell surface antigens, and reducing proinflammatory cytokines. BBR also increased protein expression levels of tight junction proteins in the mucosa and improved morphological parameters of the jejunum. Furthermore, BBR reduced the expression of signaling pathways associated with inflammation and oxidative stress, suggesting its potential in maintaining intestinal health in piglets exposed to DON.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0269749121014470?via%3Dihub.
Gong M, Duan H, Wu F, Ren Y, Gong J, Xu L, Lu F, Wang D. Berberine Alleviates Insulin Resistance and Inflammation via Inhibiting the LTB4-BLT1 Axis. Front Pharmacol. 2021 Nov 4;12:722360. doi: 10.3389/fphar.2021.722360. PMID: 34803675; PMCID: PMC8599302.

Berberine Alleviates Insulin Resistance and Inflammation via Inhibiting the LTB4-BLT1 Axis

Chronic low-grade inflammation is a significant factor in insulin resistance, often exacerbated by leukotriene B4 (LTB4) binding to its receptor BLT1, intensifying inflammation and insulin resistance. Berberine (BBR) has known anti-inflammatory properties, but its effect on the LTB4-BLT1 axis remains unclear. Through experiments using LTB4-induced Raw264.7 and HepG2 cells, BBR was found to mitigate inflammation and insulin resistance. These findings suggest that BBR may interact with BLT1, potentially modulating the LTB4-BLT1 pathway, offering a novel anti-inflammatory and anti-diabetic mechanism for BBR.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599302/.
Choi BH, Ahn IS, Kim YH, Park JW, Lee SY, Hyun CK, Do MS. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. Exp Mol Med. 2006 Dec 31;38(6):599-605. doi: 10.1038/emm.2006.71. PMID: 17202835.

Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte

Berberine (BBR), an isoquinoline alkaloid with diverse pharmacological effects, exhibits anti-adipogenic properties whose mechanism remains elusive. In our investigation, we treated 3T3-L1 cells with varying concentrations of BBR to analyze changes in adipogenic enzyme expression. BBR treatment led to reduced levels of leptin and adipogenic factors, alongside increased glycerol secretion and slightly decreased lipolytic enzyme mRNA expression. Furthermore, BBR treatment resulted in down-regulation of inflammation markers such as TNF-alpha and IL-6. Overall, our findings suggest that BBR exerts both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, primarily through the down-regulation of adipogenic enzymes and transcription factors.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/17202835/.
Kuo CL, Chi CW, Liu TY. The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett. 2004 Jan 20;203(2):127-37. doi: 10.1016/j.canlet.2003.09.002. PMID: 14732220.

The anti-inflammatory potential of berberine in vitro and in vivo

Berberine, an isoquinoline alkaloid with diverse pharmacological effects, including anti-inflammatory properties, presents an unclear mechanism of action. Given the role of cyclooxygenase-2 (COX-2) in prostaglandin synthesis, elevated during inflammation, we investigated whether berberine’s anti-inflammatory mechanism involves COX-2 regulation. In oral cancer cell lines OC2 and KB cells, berberine treatment reduced prostaglandin E2 (PGE2) production in a dose-dependent manner, with or without induction by 12-O-tetradecanoylphorbol-13-acetate (TPA). Berberine rapidly decreased COX-2 protein levels within 3 hours, without affecting enzyme activity, and inhibited activator protein 1 (AP-1) binding within 2 hours, suggesting direct AP-1 inhibition. In vivo, berberine pretreatment in Wistar rats inhibited exudate and PGE2 production in carrageenan-induced air pouches, reinforcing its anti-inflammatory effects.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0304383503005949?via%3Dihub.
Li Z, Geng YN, Jiang JD, Kong WJ. Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus. Evid Based Complement Alternat Med. 2014;2014:289264. doi: 10.1155/2014/289264. Epub 2014 Feb 11. PMID: 24669227; PMCID: PMC3942282.

Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus

Oxidative stress and inflammation play crucial roles in diabetes mellitus pathogenesis. Berberine (BBR), derived from plants like Coptis chinensis and Hydrastis canadensis, exhibits diverse pharmacological effects. Recent studies highlight its antioxidant and anti-inflammatory properties, contributing to its effectiveness against diabetes mellitus. This review summarizes BBR’s antioxidant and anti-inflammatory actions, evidenced by changes in oxidative stress markers, antioxidant enzymes, and proinflammatory cytokines in diabetic animals. BBR mitigates oxidative stress and inflammation in various tissues, including liver, adipose tissue, kidney, and pancreas. Its mechanisms involve multiple cellular kinases and signaling pathways, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2), and nuclear factor-κB (NF-κB). Further research is needed to elucidate detailed mechanisms and pathways, aiding in understanding BBR’s pharmacology in diabetes treatment and fostering the development of antidiabetic natural products.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942282/.
Li CL, Tan LH, Wang YF, Luo CD, Chen HB, Lu Q, Li YC, Yang XB, Chen JN, Liu YH, Xie JH, Su ZR. Comparison of anti-inflammatory effects of berberine, and its natural oxidative and reduced derivatives from Rhizoma Coptidis in vitro and in vivo. Phytomedicine. 2019 Jan;52:272-283. doi: 10.1016/j.phymed.2018.09.228. Epub 2018 Oct 1. PMID: 30599908.

Comparison of anti-inflammatory effects of berberine, and its natural oxidative and reduced derivatives from Rhizoma Coptidis in vitro and in vivo

Berberine (BBR), a prominent constituent of Rhizoma Coptidis (RC) in traditional medicine, exhibits potent anti-inflammatory effects. This study aimed to compare the anti-inflammatory potential of BBR and its natural derivatives, oxyberberine (OBB) and dihydroberberine (DHBB), both in vitro and in vivo, and elucidate their underlying mechanisms. LC-MS/MS analysis confirmed the presence of BBR, OBB, and DHBB in RC extract. In vitro assays revealed that pretreatment with BBR, OBB, and DHBB significantly reduced pro-inflammatory cytokines and inhibited NF-κB signaling pathway activation, with OBB demonstrating the highest efficacy. In vivo, BBR and OBB pretreatment dose-dependently alleviated inflammation in murine models, with OBB showing superior efficacy. Histopathological analysis supported the anti-inflammatory effects of OBB and BBR. These findings suggest OBB as a promising candidate for inflammation treatment, highlighting its potential therapeutic value and providing insights into RC pharmacodynamics.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0944711318305154?via%3Dihub.
Yan F, Wang L, Shi Y, Cao H, Liu L, Washington MK, Chaturvedi R, Israel DA, Cao H, Wang B, Peek RM Jr, Wilson KT, Polk DB. Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice. Am J Physiol Gastrointest Liver Physiol. 2012 Mar 1;302(5):G504-14. doi: 10.1152/ajpgi.00312.2011. Epub 2011 Dec 15. PMID: 22173918; PMCID: PMC3311435.

Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice

Inflammatory bowel disease (IBD) arises from disrupted immune responses in the intestinal mucosa, posing a significant challenge for treatment development. Berberine, a plant-derived alkaloid, traditionally used for bacterial diarrhea and intestinal parasites, has shown promise for its anti-inflammatory properties. This study investigated berberine’s efficacy in treating dextran sulfate sodium (DSS)-induced intestinal injury and colitis in mice. Berberine administration alleviated DSS-induced symptoms including body weight loss, colon shortening, and inflammation. It also reduced proinflammatory cytokine levels, preserved barrier function, and inhibited apoptosis in colonic epithelium. Additionally, berberine suppressed proinflammatory cytokine production and signaling pathways activation in colonic macrophages and epithelial cells. These findings suggest berberine as a potential therapeutic agent for gastrointestinal inflammatory disorders.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311435/.
Wang Z, Chen Z, Chen T, Yi T, Zheng Z, Fan H, Chen Z. Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis. Inflammation. 2017 Feb;40(1):221-231. doi: 10.1007/s10753-016-0472-6. PMID: 27832398.

Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis

Berberine, an active alkaloid from Rhizoma Coptidis, possesses anti-inflammatory and immunosuppressive properties. This study aimed to investigate berberine’s impact on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its underlying mechanisms. Berberine treatment significantly reduced footpad swelling, inflammatory cell infiltration, anti-OVA IgG levels, serum IgE concentration, and tetramer+CD8+ cells. It suppressed Th1-mediated cytokine production in footpad tissue, particularly IFN-γ, TNF-α, and IL-2. Berberine inhibited differentiation into Th1 cells by suppressing T-bet expression and IFN-γ secretion without affecting IL-4. Furthermore, berberine reduced lymphocyte proliferation and cytotoxicity while decreasing apoptosis and caspase-3 activity, as evidenced by altered Bax/Bcl-2 ratio and cleaved caspase-3 expression. These findings suggest that berberine mitigates Th1-mediated inflammation in OVA-induced DTH by modulating Th1 response and inhibiting apoptosis, highlighting its therapeutic potential for type IV hypersensitivity treatment.

You can read the abstract of the article at https://link.springer.com/article/10.1007/s10753-016-0472-6.
Liu M, Gao L, Zhang N. Berberine reduces neuroglia activation and inflammation in streptozotocin-induced diabetic mice. Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419866379. doi: 10.1177/2058738419866379. PMID: 31337260; PMCID: PMC6657114.

Berberine reduces neuroglia activation and inflammation in streptozotocin-induced diabetic mice

Our objective was to examine berberine’s impact on neuropathic pain and neuroglia activation in an experimental diabetes mellitus (DM) model. Diabetes was induced in mice using streptozotocin (STZ) followed by berberine administration. We assessed mechanical allodynia, thermal hyperalgesia, and activation of microglia and astrocytes. Berberine demonstrated anti-nociceptive effects in DM mice, improving mechanical thresholds and thermal latencies. It also suppressed microglia and astrocyte activation in the spinal cords of diabetic mice and reduced levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β, along with inflammatory proteins like iNOS and COX-2. These findings suggest that berberine alleviates neuropathic pain in STZ-induced diabetic mice by reducing neuroglia activation and associated inflammation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657114/.
Yang Z, Bian M, Ma J, Dong Y, Yang D, Qiu M, Gao Z. Berberine regulates pulmonary inflammatory microenvironment and decreases collagen deposition in response to bleomycin-induced pulmonary fibrosis in mice. Basic Clin Pharmacol Toxicol. 2023 Feb;132(2):154-170. doi: 10.1111/bcpt.13818. Epub 2022 Dec 14. PMID: 36433932.

Berberine regulates pulmonary inflammatory microenvironment and decreases collagen deposition in response to bleomycin-induced pulmonary fibrosis in mice

This study aimed to investigate berberine’s protective effect and potential mechanism against bleomycin (BLM)-induced fibrosis following lung injury, utilizing network pharmacology. Berberine and pulmonary fibrosis prediction targets were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In a BLM-induced fibrosis model, mice were treated with berberine, revealing that the mitogen-activated protein kinase (MAPK) signaling pathway may be involved in berberine’s mechanism against pulmonary fibrosis. Berberine treatment reduced lung inflammatory cell aggregation and down-regulated expression levels of TNF-α, IL-8, and IL-6 after 14 days, while after 42 days, it decreased expression levels of TGF-β1, PDGF-AB, HYP, and α-SMA, and inhibited collagen production. Berberine also down-regulated total p38 MAPKα and p38 MAPKα (pT180/Y182) expression, indicating anti-pulmonary fibrosis potential via the MAPK signaling pathway.

You can read the full article at https://onlinelibrary.wiley.com/doi/10.1111/bcpt.13818.
Yu ZC, Cen YX, Wu BH, Wei C, Xiong F, Li DF, Liu TT, Luo MH, Guo LL, Li YX, Wang LS, Wang JY, Yao J. Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats. World J Gastroenterol. 2019 Aug 7;25(29):3956-3971. doi: 10.3748/wjg.v25.i29.3956. PMID: 31413530; PMCID: PMC6689801.

Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats

In this study, we investigated the therapeutic mechanism of berberine (BBR) in irritable bowel syndrome (IBS). Using a rat model induced by water avoidance stress (WAS), we found that BBR alleviated mucosal inflammation, visceral hypersensitivity, and increased intestinal motility associated with IBS. BBR administration inhibited the NF-κB signaling pathway, reduced pro-inflammatory cytokines, promoted anti-inflammatory cytokines, and improved terminal ileum tissue inflammation. Moreover, BBR downregulated the expression of BDNF, TrkB, and C-kit, leading to decreased intestinal motility and visceral hypersensitivity. The higher dose of BBR exhibited superior therapeutic effects compared to the lower dose. These findings suggest that BBR mitigates intestinal inflammation, reduces motility, and alleviates visceral hypersensitivity in IBS rats through multiple mechanisms, highlighting its potential as a therapeutic agent for IBS.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689801/.
Naz I, Masoud MS, Chauhdary Z, Shah MA, Panichayupakaranant P. Anti-inflammatory potential of berberine-rich extract via modulation of inflammation biomarkers. J Food Biochem. 2022 Dec;46(12):e14389. doi: 10.1111/jfbc.14389. Epub 2022 Sep 19. PMID: 36121315.

Anti-inflammatory potential of berberine-rich extract via modulation of inflammation biomarkers

Prepared from Berberis lycium root bark using a green extraction approach, berberine-rich extract (BRE) along with its marker compound, berberine, exhibit diverse clinical applications, including anticancer, antidiarrheal, antidiabetic, antimicrobial, and anti-inflammatory activities. In this study, the therapeutic potential of BRE and berberine against inflammation was evaluated through in vitro chemiluminescence assays and in vivo carrageenan and formaldehyde-induced inflammation models in Wistar rats. Both BRE and berberine significantly reduced paw diameter and inflammation, restored antioxidant enzyme levels, and downregulated inflammatory biomarkers. The findings suggest that BRE, a cost-effective and bioequivalent alternative to berberine, holds promise as a natural remedy for inflammatory disorders, offering a safer therapeutic option compared to conventional NSAIDs.

You can read the abstract of the article at https://onlinelibrary.wiley.com/doi/10.1111/jfbc.14389.
Bakshi J, Lathar P, Mehra M, Grewal S, Dhingra D, Kumari S. Evaluation of anti-inflammatory response of berberine-loaded gum nanocomplexes in carrageenan-induced acute paw edema in rats. Pharmacol Rep. 2022 Apr;74(2):392-405. doi: 10.1007/s43440-021-00350-z. Epub 2022 Jan 5. PMID: 34984656.

Evaluation of anti-inflammatory response of berberine-loaded gum nanocomplexes in carrageenan-induced acute paw edema in rats

Berberine, known for its anti-inflammatory properties, faces limitations in clinical use due to poor bioavailability and solubility. To address this, berberine-loaded gum nanocomplexes were developed in this study, aiming to enhance its efficacy. Using a cross-linker, the nanocomplexes were prepared from gums (tragacanth and acacia gum) and berberine. These nanocomplexes demonstrated a significant reduction in carrageenan-induced paw edema in rats, along with decreased inflammatory mediator levels in plasma and paw tissue. Compared to berberine alone, the nanocomplexes exhibited superior anti-inflammatory effects, suggesting their potential as an effective treatment for inflammation. The study highlights the promising therapeutic application of berberine-loaded gum nanocomplexes, offering a novel approach to overcome berberine’s limitations in clinical utility.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/34984656/.
Azadi R, Mousavi SE, Kazemi NM, Yousefi-Manesh H, Rezayat SM, Jaafari MR. Anti-inflammatory efficacy of Berberine Nanomicelle for improvement of cerebral ischemia: formulation, characterization and evaluation in bilateral common carotid artery occlusion rat model. BMC Pharmacol Toxicol. 2021 Oct 3;22(1):54. doi: 10.1186/s40360-021-00525-7. PMID: 34600570; PMCID: PMC8487542.

Anti-inflammatory efficacy of Berberine Nanomicelle for improvement of cerebral ischemia: formulation, characterization and evaluation in bilateral common carotid artery occlusion rat model

Berberine (BBR), known for its anti-inflammatory and antioxidant properties, suffers from low oral bioavailability. In this study, a micelle formulation of BBR was developed to enhance its therapeutic efficacy, particularly in cerebral ischemia. The nano formulation exhibited favorable characteristics, with micelles smaller than 20 nm and high stability. Pretreatment with BBR and BBR-loaded micelles significantly decreased levels of inflammatory cytokines TNF-α, IL-1β, and MDA in a rat model of cerebral ischemia induced by BCCAO. Particularly, nano BBR at lower doses demonstrated superior efficacy compared to conventional BBR, suggesting its potential as a protective agent against cerebral ischemia. This study highlights the promise of BBR-loaded micelle formulation in mitigating oxidative stress and inflammation associated with cerebral ischemia.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487542/.
Shang W, Liu J, Yu X, Zhao J. [Effects of berberine on serum levels of inflammatory factors and inflammatory signaling pathway in obese mice induced by high fat diet]. Zhongguo Zhong Yao Za Zhi. 2010 Jun;35(11):1474-7. Chinese. PMID: 20822024.

[Effects of berberine on serum levels of inflammatory factors and inflammatory signaling pathway in obese mice induced by high fat diet]

The study aimed to assess berberine’s impact on serum TNF-alpha, IL-6, and adiponectin levels in obese mice induced by a high-fat diet, along with its underlying molecular mechanisms. Mice were divided into normal chow and high-fat diet groups, with the latter further subdivided into model, low-dosage berberine, and high-dosage berberine groups. Berberine administration reduced TNF-alpha and IL-6 levels in treated mice compared to the model group, with improved glucose tolerance, reduced body weight, and epididymal fat. Berberine treatment also decreased phosphorylation of IKK-beta (ser181) in liver and adipose tissue, indicating its potential in ameliorating insulin resistance and abnormal glucose metabolism in obese mice.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/20822024/.
Spatuzza C, Postiglione L, Covelli B, Ricciardone M, Benvenuti C, Mondola P, Belfiore A. Effects of berberine and red yeast on proinflammatory cytokines IL-6 and TNF-α in peripheral blood mononuclear cells (PBMCs) of human subjects. Front Pharmacol. 2014 Oct 20;5:230. doi: 10.3389/fphar.2014.00230. PMID: 25368579; PMCID: PMC4202723.

Effects of berberine and red yeast on proinflammatory cytokines IL-6 and TNF-α in peripheral blood mononuclear cells (PBMCs) of human subjects

The study aimed to assess the impact of berberine and red yeast on the release and gene expression of proinflammatory cytokines IL-6 and TNF-α in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs), associated with obesity-related inflammation. Results showed that both berberine and red yeast inhibited the release of IL-6 and TNF-α proteins induced by LPS, with a synergistic effect observed at certain concentrations. Additionally, the combination treatment significantly inhibited IL-6 and TNF-α gene expression in activated PBMCs. These findings suggest that berberine and red yeast may offer a promising pharmacological approach to mitigate obesity-related inflammation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202723/.
Li Z, Geng YN, Jiang JD, Kong WJ. Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus. Evid Based Complement Alternat Med. 2014;2014:289264. doi: 10.1155/2014/289264. Epub 2014 Feb 11. PMID: 24669227; PMCID: PMC3942282.

Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus

Oxidative stress and inflammation play crucial roles in diabetes mellitus pathogenesis. Berberine (BBR), a natural compound found in plants like Coptis chinensis and Hydrastis canadensis, exhibits diverse pharmacological activities. Recent research highlights BBR’s antioxidant and anti-inflammatory properties, contributing to its effectiveness against diabetes. This review outlines BBR’s antioxidant and anti-inflammatory effects and their underlying molecular mechanisms. BBR administration in diabetic animals demonstrates changes in oxidative stress markers, antioxidant enzymes, and proinflammatory cytokines across various tissues. BBR mitigates oxidative stress and inflammation in liver, adipose tissue, kidney, and pancreas through intricate mechanisms involving AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2) pathway, and nuclear factor-κB (NF-κB) pathway. However, further investigation is needed to fully elucidate these mechanisms, aiding in comprehending BBR’s pharmacology in diabetes treatment and fostering the development of antidiabetic natural products.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942282/.
Choi BH, Kim YH, Ahn IS, Ha JH, Byun JM, Do MS. The inhibition of inflammatory molecule expression on 3T3-L1 adipocytes by berberine is not mediated by leptin signaling. Nutr Res Pract. 2009 Summer;3(2):84-8. doi: 10.4162/nrp.2009.3.2.84. Epub 2009 Jun 30. PMID: 20016706; PMCID: PMC2788178.

The inhibition of inflammatory molecule expression on 3T3-L1 adipocytes by berberine is not mediated by leptin signaling

In our previous research, we demonstrated berberine’s dual anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, attributing the anti-adipogenicity to the down-regulation of adipogenic enzymes and transcription factors. Here, we delved deeper into berberine’s anti-inflammatory impact, assessing changes in adipokine expressions via real-time RT-PCR. Despite initially hypothesizing that berberine’s anti-adipogenicity might mediate its anti-inflammatory effect, further investigation using western blot analysis revealed no impact on the phosphorylations of STAT-3 and ERK, key players in leptin signaling. This suggests that berberine’s anti-inflammatory effect is not mediated by inhibiting leptin signal transduction. However, our findings did show that berberine down-regulates NF-κB signaling, an inflammation-related pathway, indicating that its anti-inflammatory action operates independently of leptin signaling.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788178/.
Ma J, Chan CC, Huang WC, Kuo ML. Berberine Inhibits Pro-inflammatory Cytokine-induced IL-6 and CCL11 Production via Modulation of STAT6 Pathway in Human Bronchial Epithelial Cells. Int J Med Sci. 2020 Jun 8;17(10):1464-1473. doi: 10.7150/ijms.45400. PMID: 32624703; PMCID: PMC7330667.

Berberine Inhibits Pro-inflammatory Cytokine-induced IL-6 and CCL11 Production via Modulation of STAT6 Pathway in Human Bronchial Epithelial Cells

Berberine, an isoquinoline alkaloid derived from various Chinese herbs, exhibits diverse pharmacological properties including anti-inflammatory activity. This study investigates berberine’s efficacy in mitigating allergic airway inflammation by targeting epithelial cells, pivotal in Th2-type immunity-driven allergic responses. Using the BEAS-2B human bronchial epithelial cell line, pre-treated with berberine and then activated by IL-4 plus TNF-α, we assessed cell viability and measured IL-6 and CCL11 secretion levels. While berberine didn’t affect cell viability, it significantly inhibited IL-6 and CCL11 secretion. Notably, berberine reduced nuclear STAT6 protein expression, suggesting modulation of the STAT6 signaling pathway. These findings underscore berberine’s potential as an anti-inflammatory agent in allergic airway inflammation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330667/.
Liu M, Gao L, Zhang N. Berberine reduces neuroglia activation and inflammation in streptozotocin-induced diabetic mice. Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419866379. doi: 10.1177/2058738419866379. PMID: 31337260; PMCID: PMC6657114.

Berberine reduces neuroglia activation and inflammation in streptozotocin-induced diabetic mice

We investigated berberine’s effects on neuropathic pain and neuroglia activation in an experimental diabetes mellitus (DM) model induced in mice by streptozotocin (STZ) injection. Berberine administration ameliorated mechanical allodynia and thermal hyperalgesia and reduced microglia and astrocyte activation in the spinal cords of diabetic mice. Moreover, berberine inhibited the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and inflammatory proteins (iNOS, COX-2). These findings demonstrate berberine’s anti-nociceptive effects in diabetic mice, attributed to its ability to reduce neuroglia activation and associated inflammation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657114/.
Xu X, Zhang L, Zhao Y, Xu B, Qin W, Yan Y, Yin B, Xi C, Ma L. Anti-inflammatory mechanism of berberine on lipopolysaccharide-induced IEC-18 models based on comparative transcriptomics. Mol Med Rep. 2020 Dec;22(6):5163-5180. doi: 10.3892/mmr.2020.11602. Epub 2020 Oct 14. PMID: 33174609; PMCID: PMC7646980.

Anti-inflammatory mechanism of berberine on lipopolysaccharide-induced IEC-18 models based on comparative transcriptomics

Intestinal surface epithelial cells (IECs) play a crucial role in maintaining water and electrolyte balance and nutrient absorption, but inflammation can disrupt their function. Berberine (BBR), an isoquinoline alkaloid, is known for its clinical use in treating gastrointestinal bacterial infections and inflammation. In this study, IEC-18 rat intestinal epithelial cells were treated with lipopolysaccharide (LPS) to induce inflammation, followed by BBR treatment to investigate its anti-inflammatory mechanism. Transcriptome analysis revealed that BBR treatment resulted in differential gene expression related to DNA replication, cell cycle, apoptosis, leukocyte migration, and pathways such as NF-κB and AP-1. BBR showed the ability to restrict DNA replication, inhibit cell cycle progression, promote apoptosis, suppress NF-κB and AP-1 pathways, and inhibit leukocyte migration, indicating its multifaceted anti-inflammatory effects on IECs.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646980/.
Zhai L, Huang T, Xiao HT, Wu PG, Lin CY, Ning ZW, Zhao L, Kwan HYA, Hu XJ, Wong HLX, Li XQ, Bian ZX. Berberine Suppresses Colonic Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis Through Inhibition of Cytosolic Phospholipase A2 Activity. Front Pharmacol. 2020 Nov 19;11:576496. doi: 10.3389/fphar.2020.576496. PMID: 33658925; PMCID: PMC7919193.

Berberine Suppresses Colonic Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis Through Inhibition of Cytosolic Phospholipase A2 Activity

Recent studies have linked alterations in phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) levels to ulcerative colitis (UC) pathology, with oral PC administration showing therapeutic potential. Berberine has demonstrated anti-inflammatory effects in colitic mice, yet its impact on PC metabolism remains unclear. Here, we found that berberine reduces LPC levels in DSS-induced colitic mice sera and LPS-stimulated macrophages. Cytosolic phospholipase A2a (PLA2G4A), responsible for PC hydrolysis to LPC, was up-regulated in colonic tissues and inflamed macrophages. Berberine inhibited PLA2G4A phosphorylation, suppressed pro-inflammatory TNF-alpha and IL-6 expression, and directly bound to PLA2G4A, inhibiting the MAPK/JNK pathway. These findings suggest berberine’s potential in modulating PC metabolism via PLA2G4A to alleviate colonic inflammation, offering new UC therapeutic strategies.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919193/.
Lu Y, Zhang X, He J, Dai Z, Shi P, Lu Y, Chang F. The effects of berberine on inflammatory markers in Chinese patients with metabolic syndrome and related disorders: a meta-analysis of randomized controlled trials. Inflammopharmacology. 2022 Jun;30(3):1063-1077. doi: 10.1007/s10787-022-00976-2. Epub 2022 Mar 29. PMID: 35352233; PMCID: PMC9135894.

The effects of berberine on inflammatory markers in Chinese patients with metabolic syndrome and related disorders: a meta-analysis of randomized controlled trials

A meta-analysis of randomized controlled trials (RCTs) aimed to assess the impact of berberine on inflammatory markers in metabolic syndrome (MetS) and related disorders. From 7387 screened publications, 52 studies involving 4616 patients were included. Berberine was found to significantly reduce levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) in MetS patients. However, it did not affect interleukin 1β (IL-1β) levels. These findings suggest that berberine may have a beneficial effect on inflammation in MetS and related disorders, warranting further large-scale studies for validation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135894/.
Wu YS, Li ZM, Chen YT, Dai SJ, Zhou XJ, Yang YX, Lou JS, Ji LT, Bao YT, Xuan L, Lin LN, Li CY. Berberine Improves Inflammatory Responses of Diabetes Mellitus in Zucker Diabetic Fatty Rats and Insulin-Resistant HepG2 Cells through the PPM1B Pathway. J Immunol Res. 2020 Aug 18;2020:2141508. doi: 10.1155/2020/2141508. PMID: 32908938; PMCID: PMC7450322.

Berberine Improves Inflammatory Responses of Diabetes Mellitus in Zucker Diabetic Fatty Rats and Insulin-Resistant HepG2 Cells through the PPM1B Pathway

Berberine (BBR), derived from a Chinese herb, is known for its clinical efficacy in mitigating insulin resistance (IR) and inflammation, although its underlying mechanism remains unclear. This study investigates the impact of BBR and protein phosphatase, Mg2+/Mn2+-dependent 1B (PPM1B) on IR. In ZDF rats, BBR administration significantly reduces various markers of IR and improves liver pathology, particularly with PPM1B upregulation. In HepG2-IR cells, BBR enhances glucose consumption, uptake, and alleviates inflammation. Knockdown of PPM1B exacerbates inflammatory response and glycometabolism disorder in these cells. Mechanistically, BBR treatment reverses the expression of several key signaling molecules, suggesting its regulatory role in IR progression through modulation of various pathways in the liver.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450322/.
Zhang BY, Chen M, Chen XC, Cao K, You Y, Qian YJ, Yu WK. Berberine reduces circulating inflammatory mediators in patients with severe COVID-19. Br J Surg. 2021 Jan 27;108(1):e9-e11. doi: 10.1093/bjs/znaa021. PMID: 33640910; PMCID: PMC7799351.

Berberine reduces circulating inflammatory mediators in patients with severe COVID-19

Uncontrolled cytokine storms and multiple organ dysfunction syndrome (MODS) are significant factors contributing to the severity and mortality of COVID-19 patients. Berberine, a traditional Chinese medicine with antimicrobial and anti-inflammatory properties, has been proposed for its potential in mitigating gut damage and systemic inflammation caused by SARS-CoV-2. In a prospective study involving 39 severe COVID-19 patients, berberine supplementation alongside routine therapy did not significantly alter serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), procalcitonin, and white blood cell (WBC) count over 14 days compared to routine therapy alone. However, subgroup analysis revealed that berberine had a notable effect in improving IL-6, TNF-α, and CRP levels in patients with diarrhea, a common symptom associated with COVID-19. Adverse effects were minimal, with only one patient experiencing a mild rash that resolved upon discontinuation of berberine.

You can read the abstract of the article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799351/.
Jurgiel J, Graniak A, Opyd P, Zawodny T, Lis M. The role of berberine in polycystic ovary syndrome – a summary of knowledge. Ginekol Pol. 2023 Dec 18. doi: 10.5603/gpl.95138. Epub ahead of print. PMID: 38108460.

The role of berberine in polycystic ovary syndrome – a summary of knowledge

Polycystic ovary syndrome (PCOS), affecting 5-10% of women of reproductive age, was first detailed by Stein and Leventhal in 1935. Given its diverse symptomatology, PCOS treatment often involves tailored approaches and multiple medications. Berberine, a well-established alkaloid, has emerged as a promising treatment for PCOS. Studies suggest it can alleviate hormonal imbalances, including reducing testosterone levels and FAI, increasing SHBG, and improving symptoms like hirsutism and acne. Berberine also enhances the effects of other PCOS drugs like metformin and oral contraceptives, with generally good tolerability. However, further research is needed to fully understand its mechanisms, efficacy, and long-term safety in PCOS management.

You can read the bstract of the article at https://journals.viamedica.pl/ginekologia_polska/article/view/95138.
Zhang SW, Zhou J, Gober HJ, Leung WT, Wang L. Effect and mechanism of berberine against polycystic ovary syndrome. Biomed Pharmacother. 2021 Jun;138:111468. doi: 10.1016/j.biopha.2021.111468. Epub 2021 Mar 16. PMID: 33740526.

Effect and mechanism of berberine against polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, and infertility, often accompanied by metabolic dysfunction, including metabolic syndrome (MS) and insulin resistance (IR). Berberine (BBR), the active compound in Coptis, has emerged as a promising treatment for PCOS due to its multifaceted effects and minimal side effects. Studies suggest that BBR can improve insulin resistance, reduce serum androgen levels, regulate lipid metabolism, and alleviate chronic inflammation associated with PCOS. It is often used in combination with other drugs like metformin and compound cyproterone (CPA) to enhance therapeutic outcomes in PCOS management.

You can read the full article at https://www.sciencedirect.com/science/article/pii/S0753332221002535?via%3Dihub.
Li MF, Zhou XM, Li XL. The Effect of Berberine on Polycystic Ovary Syndrome Patients with Insulin Resistance (PCOS-IR): A Meta-Analysis and Systematic Review. Evid Based Complement Alternat Med. 2018 Nov 14;2018:2532935. doi: 10.1155/2018/2532935. PMID: 30538756; PMCID: PMC6261244.

The Effect of Berberine on Polycystic Ovary Syndrome Patients with Insulin Resistance (PCOS-IR): A Meta-Analysis and Systematic Review

The aim of this study was to assess the impact of berberine (BBR) on polycystic ovary syndrome (PCOS) patients with insulin resistance (IR). A systematic search of multiple databases was conducted up to July 2018 to identify relevant randomized controlled trials. Nine studies were included in the analysis. The findings suggested that while berberine (BBR) did not significantly differ from metformin (MET) in alleviating insulin resistance or improving glycolipid metabolism and reproductive endocrine conditions, combinations of BBR with cyproterone acetate (CPA) or Chinese herbs showed potential benefits. However, definitive conclusions on the efficacy of BBR for PCOS-IR were limited by the available data. Further well-designed, randomized, double-blind, placebo-controlled trials are warranted to elucidate the mechanisms and confirm the safety and effectiveness of BBR in treating PCOS-IR.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261244/.
Ionescu OM, Frincu F, Mehedintu A, Plotogea M, Cirstoiu M, Petca A, Varlas V, Mehedintu C. Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women. Life (Basel). 2023 Jan 2;13(1):125. doi: 10.3390/life13010125. PMID: 36676074; PMCID: PMC9864590.

Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by various endocrine and metabolic irregularities, leading to fertility challenges and adverse pregnancy outcomes. Insulin resistance, often accompanying PCOS, contributes to these complications. Berberine, a compound found in medicinal herbs, possesses hypoglycemic properties and has shown promise in improving fertility and pregnancy outcomes in PCOS women with insulin resistance. Our study aims to investigate how berberine mitigates the impact of insulin resistance in PCOS, potentially enhancing fertility and pregnancy outcomes, drawing from existing pharmacological and clinical trials.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864590/.
Mirzaee F, Razmjouei P, Shahrahmani H, Vafisani F, Najaf Najafi M, Ghazanfarpour M. The effect and safety of Berberine on polycystic ovary syndrome: a systematic review. J Obstet Gynaecol. 2021 Jul;41(5):684-689. doi: 10.1080/01443615.2020.1787964. Epub 2020 Aug 19. PMID: 32811221.

The effect and safety of Berberine on polycystic ovary syndrome: a systematic review

This systematic review aims to evaluate the impact of Berberine (BBR) on women’s health, particularly focusing on its effects on polycystic ovary syndrome (PCOS) patients, providing valuable insights for both patients and healthcare providers. Through a comprehensive search of electronic databases up to July 1st, 2019, including PubMed, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL), clinical trials and randomized controlled trials assessing the effects of BBR on PCOS were identified. While BBR did not significantly affect body weight and composition, it showed a notable decrease in waist to hip ratio (WHR), hormonal profiles related to insulin resistance (IR), and insulin resistance itself (HOMA-IR). Additionally, androstenedione levels decreased significantly with BBR treatment, although no significant effects were observed on follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

You can read the full article at https://www.tandfonline.com/doi/full/10.1080/01443615.2020.1787964.
Rondanelli M, Infantino V, Riva A, Petrangolini G, Faliva MA, Peroni G, Naso M, Nichetti M, Spadaccini D, Gasparri C, Perna S. Polycystic ovary syndrome management: a review of the possible amazing role of berberine. Arch Gynecol Obstet. 2020 Jan;301(1):53-60. doi: 10.1007/s00404-020-05450-4. Epub 2020 Feb 14. PMID: 32060683; PMCID: PMC7028834.

Polycystic ovary syndrome management: a review of the possible amazing role of berberine

This narrative review aims to evaluate the potential of berberine in managing polycystic ovary syndrome (PCOS), considering its effectiveness against insulin resistance and obesity, particularly in reducing visceral adipose tissue (VAT). The review encompasses five studies involving a total of 1078 women, revealing promising results. Berberine was found to induce a redistribution of adipose tissue, improve insulin sensitivity similar to metformin, enhance lipid patterns, and ameliorate insulin resistance in theca cells, leading to improved ovulation rates and fertility outcomes. Overall, berberine appears to be safe for premenopausal women seeking pregnancy with minimal side effects. Further research is warranted to establish optimal dosage for long-term therapy.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028834/.
Ionescu OM, Frincu F, Mehedintu A, Plotogea M, Cirstoiu M, Petca A, Varlas V, Mehedintu C. Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women. Life (Basel). 2023 Jan 2;13(1):125. doi: 10.3390/life13010125. PMID: 36676074; PMCID: PMC9864590.

Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by various endocrine and metabolic abnormalities, leading to fertility challenges and adverse pregnancy outcomes. Insulin resistance plays a crucial role in PCOS-related infertility and pregnancy complications. Berberine, an alkaloid found in medicinal herbs, exhibits hypoglycemic effects and has shown promise in improving fertility and pregnancy outcomes in PCOS women with insulin resistance. Despite limited clinical trials, berberine’s potential in addressing insulin resistance in PCOS and enhancing reproductive health warrants further investigation, prompting our study to explore its mechanisms and benefits in improving fertility and pregnancy outcomes for women with PCOS.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864590/.
Xie L, Zhang D, Ma H, He H, Xia Q, Shen W, Chang H, Deng Y, Wu Q, Cong J, Wang CC, Wu X. The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials. Evid Based Complement Alternat Med. 2019 Dec 13;2019:7918631. doi: 10.1155/2019/7918631. PMID: 31915452; PMCID: PMC6930782.

The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials

The objective of this systematic review was to evaluate the effectiveness and safety of berberine in managing reproductive endocrine and metabolic outcomes in women diagnosed with polycystic ovary syndrome (PCOS). Through a comprehensive search of several databases and analysis of relevant indicators, 12 randomized controlled trials were included. The findings indicated that while berberine did not significantly improve live birth rates compared to placebo or metformin, it showed promise in reducing total testosterone levels, luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio, total cholesterol, waist circumference, and waist-to-hip ratio. However, berberine did not demonstrate a significant impact on body mass index (BMI). Moreover, berberine was not associated with an increased risk of gastrointestinal adverse events or serious events during pregnancy when compared to placebo. These results suggest that while berberine may not significantly affect live birth rates, it may offer benefits in addressing insulin resistance, dyslipidemia, and hormonal imbalances in women with PCOS compared to metformin.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930782/.
An Y, Sun Z, Zhang Y, Liu B, Guan Y, Lu M. The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment. Clin Endocrinol (Oxf). 2014 Mar;80(3):425-31. doi: 10.1111/cen.12294. Epub 2013 Aug 9. PMID: 23869585.

The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment

In this prospective study involving 150 infertile women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) treatment, we aimed to compare the clinical, metabolic, and endocrine effects of berberine versus metformin. Patients were randomized to receive either berberine, metformin, or placebo tablets for three months before ovarian stimulation. Results showed that both berberine and metformin groups exhibited significant improvements in various parameters compared to placebo, including reductions in total testosterone, free androgen index, fasting glucose, fasting insulin, and HOMA-IR, along with increases in SHBG. Moreover, berberine and metformin treatments were associated with increased pregnancy rates and decreased incidence of severe ovarian hyperstimulation syndrome. Berberine demonstrated superior outcomes compared to metformin, showing reductions in BMI, lipid parameters, and total FSH requirement, and an increased live birth rate with fewer gastrointestinal adverse events. These findings suggest that both berberine and metformin can enhance pregnancy outcomes in PCOS women undergoing IVF, with berberine showing a more favorable therapeutic profile.

You can read the abstract of the article at https://onlinelibrary.wiley.com/doi/10.1111/cen.12294.
Mishra N, Verma R, Jadaun P. Study on the Effect of Berberine, Myoinositol, and Metformin in Women with Polycystic Ovary Syndrome: A Prospective Randomised Study. Cureus. 2022 Jan 31;14(1):e21781. doi: 10.7759/cureus.21781. PMID: 35251851; PMCID: PMC8890747.

Study on the Effect of Berberine, Myoinositol, and Metformin in Women with Polycystic Ovary Syndrome: A Prospective Randomised Study

This study aimed to compare the effects of berberine, metformin, and myoinositol in women with polycystic ovary syndrome (PCOS). Subjects were randomly assigned to receive either berberine hydrochloride, metformin hydrochloride, or myoinositol twice daily for three months. Significant improvements were observed in weight, BMI, waist circumference, waist-hip ratio, fasting blood sugar, serum fasting insulin, total testosterone, free androgen index, sex hormone-binding globulin, lipid profile, and carbohydrate metabolic parameters in all groups. Berberine showed greater improvements in clinical, hormonal, and lipid parameters compared to metformin and myoinositol, while myoinositol demonstrated superior effects on carbohydrate metabolic parameters. These findings suggest that berberine may offer greater potential in reducing cardiovascular risk in PCOS patients, while myoinositol may be considered as a first-line option for those with insulin resistance without prediabetes or diabetes.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890747/.
Zhang N, Liu X, Zhuang L, Liu X, Zhao H, Shan Y, Liu Z, Li F, Wang Y, Fang J. Berberine decreases insulin resistance in a PCOS rats by improving GLUT4: Dual regulation of the PI3K/AKT and MAPK pathways. Regul Toxicol Pharmacol. 2020 Feb;110:104544. doi: 10.1016/j.yrtph.2019.104544. Epub 2019 Nov 26. PMID: 31778716.

Berberine decreases insulin resistance in a PCOS rats by improving GLUT4: Dual regulation of the PI3K/AKT and MAPK pathways

In this study, the pharmacological activities of berberine in reducing blood glucose levels and treating polycystic ovarian syndrome (PCOS) were investigated using a female Sprague-Dawley rat model of insulin-resistant PCOS induced by oral letrozole. Rats were divided into untreated and berberine-treated groups receiving different doses of berberine (400, 200, or 100 mg/kg) for 28 days. Berberine treatment effectively restored homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) values to normal levels and upregulated glucose transporter 4 (GLUT4) expression, leading to normalization of ovarian morphology. Additionally, berberine at 400 mg/kg activated the PI3K/AKT signaling pathway and suppressed the MAPK pathway. These findings suggest that berberine may alleviate PCOS pathology and insulin resistance through upregulation of GLUT4 via PI3K/AKT activation and MAPK pathway suppression.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0273230019303083?via%3Dihub.
Wei W, Zhao H, Wang A, Sui M, Liang K, Deng H, Ma Y, Zhang Y, Zhang H, Guan Y. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome. Eur J Endocrinol. 2012 Jan;166(1):99-105. doi: 10.1530/EJE-11-0616. Epub 2011 Oct 21. PMID: 22019891.

A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome

The objective of this study was to assess the effects of berberine (BBR) compared to metformin (MET) on the metabolic features of women with polycystic ovary syndrome (PCOS) and insulin resistance (IR). Eighty-nine PCOS and IR subjects were randomized into BBR+compound cyproterone acetate (CPA), MET+CPA, or placebo+CPA groups for 3 months. BBR treatment resulted in significant reductions in waist circumference, waist-to-hip ratio, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDLC), and increases in high-density lipoprotein cholesterol (HDLC) and sex hormone-binding globulin (SHBG) compared to MET or placebo. These findings suggest that BBR may improve metabolic and hormonal abnormalities in women with PCOS, possibly through changes in body composition and lipid metabolism, necessitating further controlled studies for validation.

You can read the abstract of the article at https://academic.oup.com/ejendo/article-abstract/166/1/99/6659259?redirectedFrom=fulltext&login=false.
Xia Q, Wang W, Liu Z, Xiao J, Qiao C, Zhao Y, Li B, Liu Y, Peng Y, Yang X, Shi J, Gao X, Wang D. New insights into mechanisms of berberine in alleviating reproductive disorders of polycystic ovary syndrome: Anti-inflammatory properties. Eur J Pharmacol. 2023 Jan 15;939:175433. doi: 10.1016/j.ejphar.2022.175433. Epub 2022 Dec 16. PMID: 36535493.

New insights into mechanisms of berberine in alleviating reproductive disorders of polycystic ovary syndrome: Anti-inflammatory properties

Polycystic ovary syndrome (PCOS) poses significant challenges to female reproductive health, impacting oocyte quality, embryo development, and pregnancy rates. Identifying novel therapeutic targets for PCOS-related reproductive disorders is crucial. Berberine, a renowned traditional Chinese medicine, has demonstrated efficacy in improving ovulation and live birth rates in PCOS women by targeting insulin resistance and metabolic abnormalities. However, its anti-inflammatory properties, vital in addressing PCOS-associated chronic inflammation, have received less attention. Berberine’s ability to modulate ovarian and uterine inflammation may offer fresh insights into its mechanisms of action in alleviating PCOS-related reproductive disorders. This review aims to highlight berberine’s anti-inflammatory effects in PCOS, encouraging further research into its potential as a therapeutic agent.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S001429992200694X?via%3Dihub.
Zhu TW, Li XL. Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome. Clin Exp Pharmacol Physiol. 2023 Nov;50(11):835-843. doi: 10.1111/1440-1681.13814. Epub 2023 Aug 21. PMID: 37604463.

Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome

Berberine (BBR), derived from Chinese medicinal plants, is closely associated with gut microbiota. Polycystic ovary syndrome (PCOS) is a prevalent reproductive and endocrine disorder linked to dysbiosis, an imbalance in intestinal microorganisms. Emerging evidence suggests berberine’s potential in PCOS treatment. This review explores recent findings on the interplay between berberine and gut microbiota, encompassing alterations in bacterial structure, intestinal metabolites post-BBR treatment, and the impact of gut microbiota on BBR bioavailability. Additionally, we discuss berberine’s therapeutic effects on PCOS, considering gut microbiota and potential mechanisms.

You can read the abstract of the article at https://onlinelibrary.wiley.com/doi/10.1111/1440-1681.13814.
Yu J, Ding C, Hua Z, Jiang X, Wang C. Protective effects of berberine in a rat model of polycystic ovary syndrome mediated via the PI3K/AKT pathway. J Obstet Gynaecol Res. 2021 May;47(5):1789-1803. doi: 10.1111/jog.14730. Epub 2021 Mar 11. PMID: 33709493; PMCID: PMC8252786.

Protective effects of berberine in a rat model of polycystic ovary syndrome mediated via the PI3K/AKT pathway

Background: Berberine (Ber), a Chinese herbal monomer, has demonstrated diverse pharmacological activities, particularly in lowering blood glucose and treating polycystic ovarian syndrome (PCOS). This study aimed to investigate Berberine’s effect on a PCOS rat model through the PI3K/AKT signaling pathway. PCOS was induced in rats using letrozole, followed by randomization into untreated, Berberine-treated, and metformin hydrochloride-treated groups. Berberine treatment improved fasting blood glucose, HOMA-IR, fasting insulin (FINS), and serum hormone levels in PCOS rats. Histological and apoptosis examinations of ovarian tissues revealed Berberine’s ability to restore morphological lesions and reduce apoptosis. Berberine also impacted granulosa cell proliferation and apoptosis, mediated via the PI3K/AKT pathway, as demonstrated by CCK-8 assays, flow cytometry, and western blotting. These findings suggest Berberine’s beneficial effects on PCOS involve modulating serum hormone levels, morphological lesions, insulin resistance, and cell viability, with inhibition of apoptosis, through the PI3K/AKT pathway.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252786/.
Shen HR, Xu X, Ye D, Li XL. Berberine Improves the Symptoms of DHEA-Induced PCOS Rats by Regulating Gut Microbiotas and Metabolites. Gynecol Obstet Invest. 2021;86(4):388-397. doi: 10.1159/000518040. Epub 2021 Aug 18. PMID: 34515131.

Berberine Improves the Symptoms of DHEA-Induced PCOS Rats by Regulating Gut Microbiotas and Metabolites

This study investigated berberine’s effects on polycystic ovary syndrome (PCOS) with insulin resistance (IR) using 16S rRNA sequencing and metabolomic analysis on DHEA-induced PCOS rats. Berberine treatment altered gut microbiota and metabolism, affecting Firmicutes, Bacteroidetes, and specific genera. Differential metabolites implicated in diabetes pathways were identified, suggesting berberine’s potential in PCOS-IR treatment. However, the study’s small sample size and the need for further validation and functional studies are noted. Berberine’s efficacy in ameliorating PCOS pathology by modulating gut microbiotas and metabolites underscores its therapeutic potential for PCOS-IR.

You can read the abstract of the article at https://karger.com/goi/article/86/4/388/819984/Berberine-Improves-the-Symptoms-of-DHEA-Induced.
Shen HR, Xu X, Li XL. Berberine exerts a protective effect on rats with polycystic ovary syndrome by inhibiting the inflammatory response and cell apoptosis. Reprod Biol Endocrinol. 2021 Jan 7;19(1):3. doi: 10.1186/s12958-020-00684-y. PMID: 33407557; PMCID: PMC7789273.

Berberine exerts a protective effect on rats with polycystic ovary syndrome by inhibiting the inflammatory response and cell apoptosis

Berberine (BBR), known for its pharmacological properties as an insulin sensitizer, was investigated for its effects on polycystic ovary syndrome (PCOS) in this study. Rats with PCOS were treated with BBR for six weeks, resulting in reduced insulin resistance and testosterone levels. BBR also decreased cell apoptosis rates in ovarian granulosa cells. Molecular analysis indicated that BBR suppressed the expression of various factors associated with PCOS pathology. These findings suggest that BBR may alleviate PCOS symptoms and insulin resistance by inhibiting cell apoptosis and modulating related molecular pathways.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789273/.
Li L, Li C, Pan P, Chen X, Wu X, Ng EH, Yang D. A Single Arm Pilot Study of Effects of Berberine on the Menstrual Pattern, Ovulation Rate, Hormonal and Metabolic Profiles in Anovulatory Chinese Women with Polycystic Ovary Syndrome. PLoS One. 2015 Dec 8;10(12):e0144072. doi: 10.1371/journal.pone.0144072. PMID: 26645811; PMCID: PMC4672885.

A Single Arm Pilot Study of Effects of Berberine on the Menstrual Pattern, Ovulation Rate, Hormonal and Metabolic Profiles in Anovulatory Chinese Women with Polycystic Ovary Syndrome

The study aimed to assess the impact of berberine on menstrual patterns, ovulation rates, and hormonal/metabolic profiles in anovulatory Chinese women with polycystic ovary syndrome (PCOS). Over four months, 98 out of 102 participants completed the treatment, with 14.3% experiencing a restoration of regular menses. The ovulation rate was 25.0% overall, with no significant difference between normal weight and overweight/obese groups. Berberine treatment led to reductions in sex hormone binding globulin, insulin resistance, total cholesterol, triglycerides, and low-density lipoprotein cholesterol, primarily observed in the normal weight group. These findings suggest that berberine may improve menstrual patterns and ovulation rates in anovulatory Chinese women with PCOS and modulate metabolic parameters in normal weight individuals.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672885/.
Li Y, Ma H, Zhang Y, Kuang H, Ng EH, Hou L, Wu X. Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial. Trials. 2013 Jul 18;14:226. doi: 10.1186/1745-6215-14-226. PMID: 23866924; PMCID: PMC3722087.

Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial

This paper outlines a research design aimed at investigating the effects of berberine on insulin resistance in women with polycystic ovary syndrome (PCOS). The study employs a multicenter, randomized, placebo-controlled, and double-blind trial involving 120 participants randomized into two groups. Over a 12-week period, participants will receive either berberine or a placebo orally. The primary outcome measure will be the assessment of whole-body insulin action using the hyperinsulinemic-euglycemic clamp technique. It is hypothesized that berberine administration will lead to improved insulin resistance in women with PCOS.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722087/.
Wang Y, Fu X, Xu J, Wang Q, Kuang H. Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome. Sci Rep. 2016 Jun 16;6:28089. doi: 10.1038/srep28089. PMID: 27306862; PMCID: PMC4910093.

Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, characterized by various clinical features and an unclear pathogenesis. Current treatments for PCOS focus on managing individual symptoms rather than addressing the underlying mechanism. Berberine, an alkaloid with diverse biological effects, has shown promise in alleviating PCOS-related conditions in both animal models and human studies. Utilizing systems pharmacology, potential targets of berberine relevant to PCOS were predicted, along with potential drug interactions based on the disease network. Berberine emerges as a promising polypharmacological agent for PCOS treatment and may enhance the efficacy of existing clinical drugs.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910093/.
Li Y, Zhang C, Zhang H, Zhao X, Hou L, Xu G. [Application of metabolomics in treating polycystic ovary syndrome with berberine based on ultra high performance liquid chromatography-mass spectrometry]. Se Pu. 2014 May;32(5):464-71. Chinese. doi: 10.3724/sp.j.1123.2014.01006. PMID: 25185305.

[Application of metabolomics in treating polycystic ovary syndrome with berberine based on ultra high performance liquid chromatography-mass spectrometry]

Polycystic ovary syndrome (PCOS) presents a multifaceted challenge to the health of women in their reproductive years, underscoring the need for personalized treatment approaches. This study investigated the effects of berberine treatment on overweight PCOS patients by analyzing serum samples collected before and after a three-month treatment period. Utilizing metabolomic profiling with UHPLC-q-TOF MS, metabolic changes associated with berberine treatment were examined. Patients after berberine treatment showed distinct metabolic profiles compared to before treatment, particularly in lipid metabolism-related metabolites such as phosphatidylcholines, sphingomyelin, stearic acid, and erucamide. These findings suggest that berberine treatment may enhance insulin sensitivity and address dyslipidemia in overweight PCOS patients, highlighting the potential of LC-MS-based metabolomic analysis for evaluating traditional Chinese medicine interventions.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/25185305/.
Wu XK, Wang YY, Liu JP, Liang RN, Xue HY, Ma HX, Shao XG, Ng EH; Reproductive and Developmental Network in Chinese Medicine. Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome. Fertil Steril. 2016 Sep 1;106(3):757-765.e1. doi: 10.1016/j.fertnstert.2016.05.022. Epub 2016 Jun 20. PMID: 27336209.

Reproductive and Developmental Network in Chinese Medicine. Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome

The objective of this multicenter randomized double-blinded placebo-controlled trial was to investigate whether combining berberine with letrozole would lead to higher rates of live births compared to letrozole alone in infertile women with polycystic ovary syndrome (PCOS). A total of 644 participants were randomized into letrozole, berberine, and combination groups. The study found that cumulative live births were similar between the letrozole and combination groups (36% and 34%, respectively), both superior to the berberine group (22%). Conception, pregnancy, and ovulation rates were also similar between the letrozole and combination groups and significantly higher than in the berberine group. However, berberine did not enhance fecundity in PCOS when used in combination with letrozole.

You can read the full article at https://www.fertstert.org/article/S0015-0282(16)61289-X/fulltext.
Zhao H, Xing C, Zhang J, He B. Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis. Reprod Health. 2021 Aug 18;18(1):171. doi: 10.1186/s12978-021-01207-7. PMID: 34407851; PMCID: PMC8371888.

Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis

The study aimed to compare the clinical effectiveness of various oral insulin sensitizers, including metformin, thiazolidinediones, inositols, and berberine, in treating polycystic ovary syndrome (PCOS). Through a network meta-analysis of 22 randomized controlled trials involving 1079 PCOS patients, it was found that myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones were more effective than metformin alone in improving insulin resistance and reducing total testosterone levels. Myo-inositol combined with D-chiro-inositol was particularly effective in restoring menstrual frequency, while thiazolidinediones showed superior outcomes in lipid metabolism compared to metformin.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371888/.
Yu J, Ding C, Hua Z, Jiang X, Wang C. Protective effects of berberine in a rat model of polycystic ovary syndrome mediated via the PI3K/AKT pathway. J Obstet Gynaecol Res. 2021 May;47(5):1789-1803. doi: 10.1111/jog.14730. Epub 2021 Mar 11. PMID: 33709493; PMCID: PMC8252786.

Protective effects of berberine in a rat model of polycystic ovary syndrome mediated via the PI3K/AKT pathway

Berberine (Ber), a Chinese herbal monomer, has been studied for its pharmacological effects on blood glucose reduction and polycystic ovarian syndrome (PCOS) treatment. In this investigation, a rat model of PCOS was utilized to explore Ber’s impact via the PI3K/AKT signaling pathway. Results indicated that Ber restored serum hormone levels, improved insulin resistance, and mitigated ovarian morphological lesions and apoptosis. These effects were mediated through the PI3K/AKT pathway, as demonstrated by cellular assays and pathway blockade experiments.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252786/.
Zhao FQ, Zhao Y, Liu JY, Gou YJ, Yang YQ. [Effects of berberine on LPS /NF-κB and MAPK signaling pathways in PCOS model rats]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Mar;38(2):181-186. Chinese. doi: 10.12047/j.cjap.6229.2022.029. PMID: 36031579.

[Effects of berberine on LPS /NF-κB and MAPK signaling pathways in PCOS model rats]

The objective of this study was to assess the impact of berberine on glucose and lipid metabolism, sex hormone binding protein, adiponectin, and signaling pathways in polycystic ovary syndrome (PCOS) model rats. Female SD rats were divided into control, PCOS model, berberine, metformin, and Dyne-35 groups. After 28 days of intervention, various parameters were measured. Compared to the model group, berberine treatment led to increased uterine index and secondary follicles, reduced serum LH, testosterone levels, and LH/FSH ratio, and downregulated p38-MAPK and NF-κB protein expressions in ovarian tissues. Additionally, berberine significantly lowered serum TG, insulin, and HOMA index while increasing SHBG and decreasing LPS levels, similar to metformin. This suggests that berberine may regulate sex hormone imbalance and insulin resistance in PCOS rats by modulating ovarian tissue proteins and reducing LPS levels in serum.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/36031579/.
Szczuko M, Kikut J, Szczuko U, Szydłowska I, Nawrocka-Rutkowska J, Ziętek M, Verbanac D, Saso L. Nutrition Strategy and Life Style in Polycystic Ovary Syndrome-Narrative Review. Nutrients. 2021 Jul 18;13(7):2452. doi: 10.3390/nu13072452. PMID: 34371961; PMCID: PMC8308732.

Nutrition Strategy and Life Style in Polycystic Ovary Syndrome-Narrative Review

This narrative review delves into lifestyle modifications for women with polycystic ovary syndrome (PCOS), drawing on data from the PubMed database. It explores the metabolic disruptions affecting lipid, carbohydrate, and hormonal metabolism in these individuals, alongside considerations of sleep disorders, mental health changes, oxidative stress, and inflammation. The review underscores the potential for severe health outcomes like diabetes, organ degeneration, infertility, cardiovascular issues, dysbiosis, and cancer in PCOS patients. It advocates for lifestyle adjustments, dietary changes, nutrient selection, supplementation including herbal remedies, and physical activity to mitigate these risks. While acknowledging genetic factors, it emphasizes the substantial impact of patient-driven interventions on the course and outcomes of PCOS.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308732/.
Li Y, Ma H, Zhang Y, Kuang H, Ng EH, Hou L, Wu X. Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial. Trials. 2013 Jul 18;14:226. doi: 10.1186/1745-6215-14-226. PMID: 23866924; PMCID: PMC3722087.

Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial

In this narrative review, we examine lifestyle modifications for women with polycystic ovary syndrome (PCOS) based on an analysis of the PubMed database. We explore metabolic disruptions in lipid, carbohydrate, and hormonal pathways, alongside factors like sleep disorders, mental health changes, oxidative stress, and inflammation. These issues often lead to severe health complications including diabetes, organ degeneration, infertility, cardiovascular diseases, dysbiosis, and cancer. The review advocates for lifestyle changes, dietary adjustments, supplementation with herbs, and regular physical activity to mitigate these risks, emphasizing the substantial impact of patient-driven interventions on PCOS outcomes, while acknowledging genetic influences.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308732/.
Xie L, Zhang D, Ma H, He H, Xia Q, Shen W, Chang H, Deng Y, Wu Q, Cong J, Wang CC, Wu X. The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials. Evid Based Complement Alternat Med. 2019 Dec 13;2019:7918631. doi: 10.1155/2019/7918631. PMID: 31915452; PMCID: PMC6930782.

The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials

This study aimed to evaluate the efficacy and safety of berberine in women with polycystic ovary syndrome (PCOS) regarding reproductive endocrine and metabolic outcomes. Twelve randomized controlled trials were analyzed, indicating that berberine had comparable live birth rates to placebo or metformin but lower rates compared to letrozole. Berberine demonstrated significant reductions in total testosterone, LH/FSH ratio, total cholesterol, waist circumference, and waist-to-hip ratio compared to placebo or metformin. However, it did not significantly affect BMI. Importantly, berberine did not increase gastrointestinal adverse events or serious pregnancy-related complications compared to placebo. Thus, while berberine may not enhance live birth rates, it shows promise in improving insulin resistance, dyslipidemia, and androgen levels in PCOS women, surpassing metformin in certain aspects.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930782/.
Wang Z, Nie K, Su H, Tang Y, Wang H, Xu X, Dong H. Berberine improves ovulation and endometrial receptivity in polycystic ovary syndrome. Phytomedicine. 2021 Oct;91:153654. doi: 10.1016/j.phymed.2021.153654. Epub 2021 Jul 12. PMID: 34333328.

Berberine improves ovulation and endometrial receptivity in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is characterized by reproductive and endocrine abnormalities, with uncertain treatment effects on ovulation and endometrial receptivity. This study aimed to assess berberine’s impact on PCOS and its mechanism. Using a rat model induced by testosterone propionate, groups were established: model (Mod), low-dose berberine (BL), high-dose berberine (BH), metformin (Met), and control (Con). Berberine reversed increased cystic follicles and decreased corpus luteum, reduced LH and TC levels, and improved glucose tolerance without affecting insulin or HOMA-IR. Berberine upregulated LHCGR and CYP19A1, improving ovulation, while downregulating αvβ3 and LPAR3, enhancing endometrial receptivity.

You can read the full article at https://www.sciencedirect.com/science/article/pii/S0944711321001975?via%3Dihub.
Blais JE, Huang X, Zhao JV. Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. Drugs. 2023 Apr;83(5):403-427. doi: 10.1007/s40265-023-01841-4. Epub 2023 Mar 21. PMID: 36941490.

Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

Berberine, a nutraceutical known for improving lipid metabolism, may exhibit sex-specific effects on sex hormones and lipids. This study aimed to review berberine’s efficacy and safety for dyslipidemia treatment, considering potential sex disparities. Eighteen studies (n = 1788 participants) mainly from mainland China and Hong Kong were analyzed. Berberine reduced LDL cholesterol, total cholesterol, triglycerides, and apolipoprotein B, while increasing HDL cholesterol. Notably, the effect on HDL cholesterol differed between women and men. Gastrointestinal adverse events were more frequent with berberine. Large-scale trials considering sex differences and clinical outcomes are warranted.

You can read the full article at https://link.springer.com/article/10.1007/s40265-023-01841-4.
Doggrell SA. Berberine–a novel approach to cholesterol lowering. Expert Opin Investig Drugs. 2005 May;14(5):683-5. doi: 10.1517/13543784.14.5.683. PMID: 15926873.

Berberine–a novel approach to cholesterol lowering

While statins effectively lower LDL-cholesterol levels and reduce coronary artery disease-related mortality and morbidity, residual risk remains. Berberine, through a distinct mechanism involving stabilization of LDL receptor mRNA, also lowers LDL-cholesterol levels. Studies in hamsters and humans with hypercholesterolemia have shown reductions in total serum cholesterol, LDL-cholesterol, and triglyceride levels with berberine administration. Although berberine’s lipid-lowering profile resembles that of statins due to their shared LDL receptor upregulation, berberine’s additional effects like antihypertensive and antiarrhythmic properties may render it beneficial in cardiovascular disease treatment, despite not being a primary alternative to statins for lipid-lowering therapy.

You can read the abstract of the article at https://www.tandfonline.com/doi/abs/10.1517/13543784.14.5.683.
Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004 Dec;10(12):1344-51. doi: 10.1038/nm1135. Epub 2004 Nov 7. PMID: 15531889.

Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins

We have discovered berberine (BBR), a compound derived from a Chinese herb, as a novel cholesterol-lowering medication. In a study involving 32 hypercholesterolemic patients, oral administration of BBR for 3 months resulted in a 29% reduction in serum cholesterol, a 35% decrease in triglycerides, and a 25% decrease in LDL-cholesterol. Treatment of hyperlipidemic hamsters with BBR showed a significant decrease in serum cholesterol by 40% and LDL-cholesterol by 42%, accompanied by substantial increases in hepatic LDL receptor (LDLR) mRNA and protein levels. Through experiments with human hepatoma cells, we demonstrated that BBR enhances LDLR expression independently of sterol regulatory element binding proteins but relies on ERK activation. BBR’s mechanism involves post-transcriptional upregulation of LDLR mRNA stability. Additionally, utilizing a luciferase reporter system, we pinpointed the 5′ proximal segment of the LDLR mRNA 3′ untranslated region as responsible for BBR’s regulatory effect. These findings underscore BBR as a promising hypolipidemic agent with a distinct mechanism from statin drugs.

You can read the abstract of the article at https://pubmed.ncbi.nlm.nih.gov/15531889/.
Zhao JV, Yeung WF, Chan YH, Vackova D, Leung JYY, Ip DKM, Zhao J, Ho WK, Tse HF, Schooling CM. Effect of Berberine on Cardiovascular Disease Risk Factors: A Mechanistic Randomized Controlled Trial. Nutrients. 2021 Jul 26;13(8):2550. doi: 10.3390/nu13082550. PMID: 34444711; PMCID: PMC8401658.

Effect of Berberine on Cardiovascular Disease Risk Factors: A Mechanistic Randomized Controlled Trial

Cardiovascular disease (CVD) poses a significant global health challenge, prompting exploration into traditional Chinese medicine’s potential, like berberine, to mitigate CVD risk factors. Yet, berberine’s impact, particularly in men and its potential pathway via testosterone, remains underexplored. In a randomized, double-blind, placebo-controlled trial in Hong Kong involving 84 Chinese men with hyperlipidemia, berberine (500 mg orally, twice a day) or placebo was administered for 12 weeks. Berberine exhibited larger reductions in total cholesterol and high-density lipoprotein cholesterol after 12 weeks, potentially altering low-density lipoprotein-cholesterol (LDL-c) and testosterone levels. No serious adverse events occurred. Berberine emerges as a promising cholesterol-lowering treatment, possibly influencing testosterone in men, suggesting sex-specific effects deserving further investigation for drug repositioning and healthcare strategies.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401658/.
Derosa G, D’Angelo A, Bonaventura A, Bianchi L, Romano D, Maffioli P. Effects of berberine on lipid profile in subjects with low cardiovascular risk. Expert Opin Biol Ther. 2013 Apr;13(4):475-82. doi: 10.1517/14712598.2013.776037. Epub 2013 Feb 27. PMID: 23441841.

Effects of berberine on lipid profile in subjects with low cardiovascular risk

Research design and methods involved 144 Caucasian subjects who underwent a 6-month run-in period of diet and physical activity before randomization to receive placebo or berberine 500 mg twice daily for 3 months in a double-blind, placebo-controlled design. After a 2-month washout period with only diet and physical activity, patients resumed either berberine or placebo for another 3 months. Anthropometric and metabolic parameters were evaluated throughout the study. Results showed a decrease in body weight and BMI after the run-in period, with berberine significantly reducing total cholesterol, triglycerides, and LDL cholesterol, while increasing HDL cholesterol compared to placebo. Lipid profile worsened during the washout period but improved upon reintroduction of berberine, demonstrating its efficacy and safety in mildly improving lipid profile in low cardiovascular risk subjects.

You can read the full article at https://www.tandfonline.com/doi/full/10.1517/14712598.2013.776037.
Cicero AF, Rovati LC, Setnikar I. Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents. A single-blind clinical investigation. Arzneimittelforschung. 2007;57(1):26-30. doi: 10.1055/s-0031-1296582. PMID: 17341006.

Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents

Berberine (BERB) and a combination (COMB) of berberine with policosanol, red yeast extract, folic acid, and astaxanthin were orally administered daily for 4 weeks to 40 subjects with moderate dyslipidemias divided into two parallel groups of 20 subjects each. Measurements of total cholesterol (TC), LDL, HDL, non-HDL, ApoB, ApoA, Lp(a), and triglycerides (TG) were taken before and after treatments. Both BERB and COMB significantly reduced TC (by 16% and 20%), LDL (by 20% and 25%), ApoB (by 15% and 29%), and TG (by 22% and 26%), while increasing HDL (by 6.6% and 5.1%). No adverse events or liver transaminase or CPK impairments were observed. In conclusion, food supplements containing natural products like berberine, policosanol, red yeast extracts, folic acid, and astaxanthin could be a helpful adjunct to dietary and lifestyle changes in correcting dyslipidemias and reducing cardiovascular risk in individuals with moderate mixed dyslipidemias.

You can read the abstract of the article at https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0031-1296582.
Wang Y, Yi X, Ghanam K, Zhang S, Zhao T, Zhu X. Berberine decreases cholesterol levels in rats through multiple mechanisms, including inhibition of cholesterol absorption. Metabolism. 2014 Sep;63(9):1167-77. doi: 10.1016/j.metabol.2014.05.013. Epub 2014 Jun 4. PMID: 25002181.

Berberine decreases cholesterol levels in rats through multiple mechanisms, including inhibition of cholesterol absorption

The objective was to determine the mechanisms of action of berberine (BBR) on cholesterol homeostasis using in vivo and in vitro models. Male Sprague-Dawley rats were fed either a normal control diet or an atherogenic diet containing high fat, cholesterol, and cholic acid, with varying doses of BBR administered for 8 weeks. BBR treatment significantly reduced plasma total cholesterol and non-HDL cholesterol levels, as well as the fractional dietary cholesterol absorption rate. Additionally, BBR inhibited cholesterol micellarization, decreased cholesterol uptake by cells, and suppressed gene and protein expressions of acyl-coenzyme A:cholesterol acyltransferase-2. These findings suggest that BBR lowers blood cholesterol levels by inhibiting intestinal absorption and interfering with intraluminal cholesterol micellarization and enterocyte cholesterol uptake and secretion.

You can read the abstract of the article at https://www.metabolismjournal.com/article/S0026-0495(14)00162-0/abstract.
Yang L, Zhu W, Zhang X, Zhou X, Wu W, Shen T. Efficacy and safety of berberine for several cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials. Phytomedicine. 2023 Apr;112:154716. doi: 10.1016/j.phymed.2023.154716. Epub 2023 Feb 12. PMID: 36805484.

Efficacy and safety of berberine for several cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials

Background: Berberine is commonly used as an adjunct therapy for various cardiovascular diseases (CVDs), although its efficacy remains debated. This study aimed to assess the effectiveness and safety of berberine in CVDs through a systematic review and meta-analysis of randomized controlled trials (RCTs). Forty-four RCTs involving 4606 patients were included. Berberine alone showed no significant differences compared to routine therapy or statins in improving lipid profiles, but it significantly reduced National Institute of Health Stroke Scale (NIHSS) score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intima-media thickness (IMT). Combination therapy with berberine and statins showed significant improvements in lipid profiles, NIHSS score, hs-CRP, TNF-α, IMT, Crouse score, and unstable plaque numbers. Adverse reactions did not significantly differ between groups. Although promising, the results warrant caution due to limitations in existing research quality, emphasizing the need for high-quality RCTs to provide more robust evidence.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0944711323000740?via%3Dihub.
Hu Y, Ehli EA, Kittelsrud J, Ronan PJ, Munger K, Downey T, Bohlen K, Callahan L, Munson V, Jahnke M, Marshall LL, Nelson K, Huizenga P, Hansen R, Soundy TJ, Davies GE. Lipid-lowering effect of berberine in human subjects and rats. Phytomedicine. 2012 Jul 15;19(10):861-7. doi: 10.1016/j.phymed.2012.05.009. Epub 2012 Jun 26. PMID: 22739410.

Lipid-lowering effect of berberine in human subjects and rats

Due to the severe adverse effects and limited efficacy of current pharmacological treatments for obesity, research has shifted towards natural product-derived drugs. Previous studies have shown that berberine, an alkaloid from traditional Chinese herbs, inhibits fat accumulation both in vitro and in vivo. In this pilot study, obese Caucasian subjects were orally administered 500 mg of berberine three times daily for twelve weeks. Berberine treatment resulted in mild weight loss (average 5 lbs/subject) and significantly reduced blood lipid levels (23% decrease in triglycerides and 12.2% decrease in cholesterol) in human subjects. Similar lipid-lowering effects were observed in a Sprague-Dawley rat experiment (34.7% decrease in triglycerides and 9% decrease in cholesterol). Berberine treatment did not significantly alter cortisol, calcitriol, ACTH, TSH, FT4, or SHBG levels, but there was a notable increase in calcitriol levels (mean 59.5% increase). Blood inflammatory factors and erythrocyte sedimentation rate remained unaffected by berberine treatment, and tests for hematological, cardiovascular, liver, and kidney function showed no adverse effects. Overall, this study underscores berberine’s potency as a lipid-lowering agent with a moderate weight loss effect and potential implications in osteoporosis treatment/prevention.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S0944711312001870?via%3Dihub.
Martinez-Martin F, Corbella E, Sarasa I, Trias F, Petitbò D, Licerán M, Sánchez-Hernández RM, Martin D, Sánchez A, Arnás C, de Dios S, Florido M, Pintó X. Effects of treatment with monacolin K, berberine and coenzyme Q10 on lipid metabolism in patients with moderate cardiovascular risk. Semergen. 2022 Sep;48(6):403-410. doi: 10.1016/j.semerg.2022.04.005. Epub 2022 May 20. PMID: 35606250.

Effects of treatment with monacolin K, berberine and coenzyme Q10 on lipid metabolism in patients with moderate cardiovascular risk

The objective of this clinical trial was to assess the efficacy and safety of a nutraceutical preparation containing monacolin K, berberine, and coenzyme Q10 (Lipok®) in patients with moderate hypercholesterolemia and cardiovascular risk. Patients either received Lipok® or a placebo, and their clinical and laboratory variables were analyzed over six months. Results showed a significant reduction in LDL-C levels in the Lipok® group compared to the placebo group after three months of treatment, with no significant changes in HDL-C, triglycerides, or lipoprotein(a). The intervention demonstrated good tolerance and safety, suggesting that the combination of monacolin K, berberine, and coenzyme Q10 effectively lowers LDL-C and is safe for managing hypercholesterolemia in patients with moderate cardiovascular risk.

You can read the full article at https://www.sciencedirect.com/science/article/abs/pii/S113835932200106X?via%3Dihub.
Wang Y, Jia X, Ghanam K, Beaurepaire C, Zidichouski J, Miller L. Berberine and plant stanols synergistically inhibit cholesterol absorption in hamsters. Atherosclerosis. 2010 Mar;209(1):111-7. doi: 10.1016/j.atherosclerosis.2009.08.050. Epub 2009 Sep 4. PMID: 19782362.

Berberine and plant stanols synergistically inhibit cholesterol absorption in hamsters

This study investigated the efficacy and mechanism of berberine (BBR), plant stanols (PS), and their combination on plasma lipids in male Golden Syrian hamsters fed a cholesterol-rich diet. After four weeks of supplementation, BBR and PS individually significantly reduced plasma total and nonHDL-cholesterol levels, while the combination of BBRPS showed marked improvement in cholesterol-lowering efficacy compared to either alone. Both BBR and PS inhibited cholesterol absorption but increased cholesterol synthesis, with a synergistic effect observed when combined. Plasma cholesterol levels correlated with absorption rates, and BBRPS upregulated key genes involved in bile acid synthesis. Furthermore, the combination significantly reduced plasma triglycerides, suggesting a combined action on lipid metabolism. These findings propose a potential mechanism for BBR’s cholesterol-lowering effects involving inhibition of absorption and stimulation of bile acid synthesis, augmented by PS, highlighting a synergistic approach in managing plasma lipids.

You can read the full article at https://www.atherosclerosis-journal.com/article/S0021-9150(09)00712-6/abstract.
Kong WJ, Wei J, Zuo ZY, Wang YM, Song DQ, You XF, Zhao LX, Pan HN, Jiang JD. Combination of simvastatin with berberine improves the lipid-lowering efficacy. Metabolism. 2008 Aug;57(8):1029-37. doi: 10.1016/j.metabol.2008.01.037. PMID: 18640378.

Combination of simvastatin with berberine improves the lipid-lowering efficacy

We’ve identified berberine (BBR) as a novel cholesterol-lowering agent by stabilizing low-density lipoprotein receptor (LDLR) messenger RNA. Given its distinct mechanism from statins, we investigated BBR’s lipid-lowering activity in combination with simvastatin (SIMVA). In hyperlipidemic rats, BBR combined with SIMVA significantly reduced serum LDL cholesterol by 46.2%, outperforming monotherapies (BBR: 26.8%; SIMVA: 28.3%) and mirroring SIMVA at 12 mg/(kg d) (43.4%). Enhanced reduction in triglycerides was also observed with the combination. Moreover, the combination upregulated LDLR mRNA in rat livers by 1.6-fold compared to monotherapies, resulting in improved liver histology. In hypercholesterolemic patients, the combination therapy demonstrated superior lipid-lowering effects compared to monotherapies, suggesting a promising new regimen for hypercholesterolemia.

You can read the abstract of the article at https://www.metabolismjournal.com/article/S0026-0495(08)00070-X/abstract.
Derosa G, Maffioli P, Cicero AF. Berberine on metabolic and cardiovascular risk factors: an analysis from preclinical evidences to clinical trials. Expert Opin Biol Ther. 2012 Aug;12(8):1113-24. doi: 10.1517/14712598.2012.704014. PMID: 22780092.

Berberine on metabolic and cardiovascular risk factors: an analysis from preclinical evidences to clinical trials

Recent research has highlighted the potential of the natural alkaloid berberine in managing type 2 diabetes mellitus and hypercholesterolemia, conditions associated with increased cardiovascular disease risk. Berberine has shown efficacy in improving glycemic control and lipid profiles, offering promise for diabetes treatment and cardiovascular disease prevention. Ongoing investigations aim to further elucidate berberine’s pharmacological activities and explore the development of analogs with improved bioavailability. Future studies should focus on assessing berberine’s impact on organ damage markers and its safety profile, particularly in longer trials and within the European population, either alone or in combination with other anti-hyperlipidemic or anti-diabetic drugs.

You can read the full article at https://www.tandfonline.com/doi/full/10.1517/14712598.2012.704014.
Ilyas Z, Perna S, Al-Thawadi S, Alalwan TA, Riva A, Petrangolini G, Gasparri C, Infantino V, Peroni G, Rondanelli M. The effect of Berberine on weight loss in order to prevent obesity: A systematic review. Biomed Pharmacother. 2020 Jul;127:110137. doi: 10.1016/j.biopha.2020.110137. Epub 2020 Apr 27. PMID: 32353823.

The effect of Berberine on weight loss in order to prevent obesity: A systematic review

This study offers a comprehensive evaluation of Berberine’s efficacy in managing obesity and associated metabolic effects, drawing from in vitro, animal, and human studies. Berberine demonstrates diverse mechanisms of action, including modulation of gut microbiota, inhibition of glucose metabolism enzymes, suppression of adipocyte differentiation, and regulation of hepatic gluconeogenesis and lipid levels. These effects are observed across various dosage ranges in preclinical models, with corresponding findings in human studies. Berberine shows promise in mitigating obesity-related complications and offers potential as a therapeutic agent for obesity treatment and prevention.

You can read the full article at https://www.sciencedirect.com/science/article/pii/S0753332220303292?via%3Dihub.
Li XY, Zhao ZX, Huang M, Feng R, He CY, Ma C, Luo SH, Fu J, Wen BY, Ren L, Shou JW, Guo F, Chen Y, Gao X, Wang Y, Jiang JD. Effect of Berberine on promoting the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters. J Transl Med. 2015 Aug 27;13:278. doi: 10.1186/s12967-015-0629-3. PMID: 26310319; PMCID: PMC4549888.

Effect of Berberine on promoting the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters

In this study, we investigated the impact of Berberine (BBR) on cholesterol excretion in high-fat diet-induced hyperlipidemic hamsters. The results showed that BBR treatment significantly reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels in hyperlipidemic hamsters in a dose- and time-dependent manner, without observable side effects on liver function. Notably, BBR facilitated the excretion of cholesterol from the liver into the bile, providing insights into its cholesterol-lowering mechanism through enhanced biliary cholesterol excretion, a pathway not previously reported. These findings underscore the potential of BBR as a therapeutic agent for hyperlipidemia management.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549888/.
Affuso F, Ruvolo A, Micillo F, Saccà L, Fazio S. Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis. 2010 Nov;20(9):656-61. doi: 10.1016/j.numecd.2009.05.017. Epub 2009 Aug 20. PMID: 19699071.

Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study

In this randomized, double-blind, placebo-controlled study, we assessed the effects of a nutraceutical combination (NC) comprising 500 mg berberine, 200 mg red yeast rice, and 10 mg policosanols on cholesterol levels and endothelial function in hypercholesterolemic patients. Fifty participants were assigned to either NC or placebo for 6 weeks, followed by an open-label extension with NC for all participants. Results revealed significant reductions in total cholesterol and LDL-cholesterol levels in the NC group compared to placebo, along with improved endothelial-dependent flow-mediated dilation (FMD). After the extension phase, triglyceride levels decreased, and insulin sensitivity improved in patients with insulin resistance at baseline. No adverse effects were reported, suggesting the safety and efficacy of NC in managing hypercholesterolemia and improving endothelial function.

You can read the abstract of the article at https://www.nmcd-journal.com/article/S0939-4753(09)00139-2/abstract.
Spigoni V, Aldigeri R, Antonini M, Micheli MM, Fantuzzi F, Fratter A, Pellizzato M, Derlindati E, Zavaroni I, Bonadonna RC, Dei Cas A. Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results from a Randomized, Double Blind, Placebo-Controlled Study. Int J Mol Sci. 2017 Jul 12;18(7):1498. doi: 10.3390/ijms18071498. PMID: 28704936; PMCID: PMC5535988.

Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results from a Randomized, Double Blind, Placebo-Controlled Study

A double-blind, placebo-controlled phase II study evaluated the efficacy of a new nutraceutical formulation (containing berberine 200 mg, monacolin K 3 mg, chitosan 10 mg, and coenzyme Q 10 mg) in lowering non-HDL cholesterol in individuals with levels ≥160 mg/dL. Thirty-nine subjects were randomized, and after 12 weeks of treatment, the intervention group showed significant reductions in non-HDL cholesterol (-30 ± 20 mg/dL), LDL cholesterol (-31 ± 18 mg/dL), and apolipoprotein B levels compared to placebo. Pro-inflammatory markers, hormonal levels, PCSK9, and endothelial progenitor cell numbers remained stable. The intervention was well tolerated, with few adverse events reported, suggesting potential as a therapeutic strategy in dyslipidemic individuals for primary prevention.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535988/.
Zamani M, Zarei M, Nikbaf-Shandiz M, Hosseini S, Shiraseb F, Asbaghi O. The effects of berberine supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis. Front Nutr. 2022 Oct 14;9:1013055. doi: 10.3389/fnut.2022.1013055. PMID: 36313096; PMCID: PMC9614282.

The effects of berberine supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis

Cardiovascular disease (CVD) is a significant health concern, and herbal medicine, particularly Berberine (BBR), has garnered attention for its potential in managing CVD risk factors. To address the ongoing debate surrounding BBR’s efficacy, a meta-analysis was conducted, compiling data from randomized controlled trials (RCTs) up to July 2022. The results revealed that BBR supplementation significantly reduced triglycerides, total cholesterol, low-density lipoprotein, fasting blood glucose, insulin, HbA1c, HOMA-IR, systolic blood pressure, weight, and body mass index, while increasing high-density lipoprotein. Optimal BBR dosage varied for different parameters, with favorable outcomes observed over specific time frames. Overall, BBR supplementation demonstrated improvements in lipid profile, blood glucose regulation, obesity indicators, and blood pressure, suggesting its potential in managing CVD risk factors.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614282/.
Spigoni V, Aldigeri R, Antonini M, Micheli MM, Fantuzzi F, Fratter A, Pellizzato M, Derlindati E, Zavaroni I, Bonadonna RC, Dei Cas A. Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results from a Randomized, Double Blind, Placebo-Controlled Study. Int J Mol Sci. 2017 Jul 12;18(7):1498. doi: 10.3390/ijms18071498. PMID: 28704936; PMCID: PMC5535988.

Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results from a Randomized, Double Blind, Placebo-Controlled Study

Elevated non high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol levels pose significant risks for cardiovascular (CV) mortality, with no established threshold. A novel combination of nutraceuticals comprising berberine 200 mg, monacolin K 3 mg, chitosan 10 mg, and coenzyme Q10 mg has emerged with promising lipid-lowering properties. This study aimed to assess the efficacy of this formulation in reducing non-HDL cholesterol levels compared to placebo over 12 weeks in individuals with non-HDL-cholesterol levels ≥160 mg/dL. In a double-blind phase II placebo-controlled trial involving 39 subjects, the intervention led to significant reductions in non-HDL cholesterol, LDL cholesterol, and apolipoprotein B levels compared to placebo. The intervention was well-tolerated, with no significant changes observed in pro-inflammatory markers, hormonal levels, PCSK9, or endothelial progenitor cell counts. Three adverse events occurred, but the tested nutraceutical formulation shows promise as a potential therapeutic strategy for dyslipidemic individuals in primary prevention.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535988/.
Zhou X, Ren F, Wei H, Liu L, Shen T, Xu S, Wei J, Ren J, Ni H. Combination of berberine and evodiamine inhibits intestinal cholesterol absorption in high fat diet induced hyperlipidemic rats. Lipids Health Dis. 2017 Dec 11;16(1):239. doi: 10.1186/s12944-017-0628-x. PMID: 29228954; PMCID: PMC5725942.

Combination of berberine and evodiamine inhibits intestinal cholesterol absorption in high fat diet induced hyperlipidemic rats

Hyperlipidemia, characterized by elevated serum lipid levels, is a prevalent condition often associated with cardiovascular disease (CVD). Berberine and evodiamine, derived from traditional Chinese herbs, have been suggested to regulate lipid metabolism. This study aimed to explore the lipid-lowering effects of their combination in hyperlipidemic rats. After inducing hyperlipidemia in rats with a high-fat diet for 4 weeks, berberine (B]B), evodiamine (EV), and their combination (BB + EV) were orally administered for another 4 weeks. Results showed reduced serum cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels, along with decreased hepatic total cholesterol in rats treated with the berberine-evodiamine combination. Gas chromatography analysis indicated a significant improvement in plasma ß-Sitosterol levels, suggesting reduced cholesterol absorption activity. Immunohistochemical analysis revealed down-regulated expressions of intestinal NPC1L1, ACAT2, and ApoB48 in rats treated with BB + EV. These findings suggest that the combination of berberine and evodiamine may offer a promising preventive approach against hyperlipidemia, partly through inhibiting cholesterol absorption in the intestine.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725942/.
Heidarian E, Rafieian-Kopaei M, Khoshdel A, Bakhshesh M. Metabolic effects of berberine on liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: an additional mechanism for the hypolipidemic effects of berberine. Asian Pac J Trop Biomed. 2014 May;4(Suppl 1):S429-35. doi: 10.12980/APJTB.4.2014C474. PMID: 25183123; PMCID: PMC4025298.

Metabolic effects of berberine on liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: an additional mechanism for the hypolipidemic effects of berberine

The objective of this study was to assess the impact of berberine (BBR) on liver phosphatidate phosphohydrolase (PAP) activity and plasma lipid levels in rats fed high lipogenic and normal diets. Forty rats were divided into five groups receiving different diet and treatment combinations. Results showed that BBR supplementation significantly reduced PAP activity, plasma triglyceride, total cholesterol, very low-density lipoprotein, and malondialdehyde levels compared to the lipogenic diet group. Moreover, BBR led to a notable decrease in liver triglyceride and cholesterol levels, as well as in the atherogenic index, suggesting its potential effectiveness in mitigating lipid abnormalities and liver triglyceride accumulation associated with hyperlipidemia, with minimal side effects.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025298/.
Zhang L, Wu X, Yang R, Chen F, Liao Y, Zhu Z, Wu Z, Sun X, Wang L. Effects of Berberine on the Gastrointestinal Microbiota. Front Cell Infect Microbiol. 2021 Feb 19;10:588517. doi: 10.3389/fcimb.2020.588517. PMID: 33680978; PMCID: PMC7933196.

Effects of Berberine on the Gastrointestinal Microbiota

Berberine, a traditional Chinese remedy, has shown promise in treating various diseases like obesity, diabetes, and atherosclerosis, with ongoing clinical trials exploring its potential in cardiovascular, gastrointestinal, and endocrine disorders. Despite its clinical benefits and low toxicity, the precise mechanism behind its lipid-lowering and insulin-sensitizing effects remains unclear. One plausible explanation is its impact on the gastrointestinal microbiota. This review aims to elucidate the role of the gut microbiota in berberine treatment by summarizing its pharmacological effects in animals and humans. A comprehensive search across electronic databases was conducted to compile evidence supporting berberine’s regulation of the gastrointestinal microbiota.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933196/.
Yang F, Gao R, Luo X, Liu R, Xiong D. Berberine influences multiple diseases by modifying gut microbiota. Front Nutr. 2023 Aug 3;10:1187718. doi: 10.3389/fnut.2023.1187718. PMID: 37599699; PMCID: PMC10435753.

Berberine influences multiple diseases by modifying gut microbiota

Berberine (BBR), an isoquinoline alkaloid abundant in plants like Coptis chinensis Franch, exhibits limited bioavailability but exerts significant influence on various diseases by interacting with the gut microbiota. Its impact spans conditions including diabetes, hyperlipidemia, atherosclerosis, liver and intestinal diseases, mental disorders, and autoimmune diseases. This review systematically explores these interactions and their implications, detailing alterations in gut microbiota following different doses of berberine intervention and potential clinical outcomes. Such insights aim to inform the judicious utilization of BBR in future clinical practice.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10435753/.
Wang H, Zhang H, Gao Z, Zhang Q, Gu C. The mechanism of berberine alleviating metabolic disorder based on gut microbiome. Front Cell Infect Microbiol. 2022 Aug 25;12:854885. doi: 10.3389/fcimb.2022.854885. PMID: 36093200; PMCID: PMC9452888.

The mechanism of berberine alleviating metabolic disorder based on gut microbiome

As socioeconomic progress and lifestyle improvements continue, metabolic syndrome has gained increasing attention. Recent research highlights the intricate connection between the gut microbiome and various metabolic diseases such as obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. Berberine (BBR), a natural compound, has emerged as a significant therapeutic agent for metabolic disorders, with studies demonstrating its ability to alleviate pathological conditions. This effect is attributed to BBR’s regulation of the gut microbiota, influencing its absorption, utilization, and structural composition. Mechanisms include modulation of nitroreductase-producing bacteria, enhancement of intestinal barrier function, inflammation reduction, regulation of bile acid signaling pathways, and the bacteria-gut-brain axis. Our study aims to elucidate the therapeutic properties of berberine further, shedding light on its role in mitigating metabolic disorders through gut microbiota regulation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9452888/.
Tian Y, Cai J, Gui W, Nichols RG, Koo I, Zhang J, Anitha M, Patterson AD. Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation. Drug Metab Dispos. 2019 Feb;47(2):86-93. doi: 10.1124/dmd.118.083691. Epub 2018 Nov 8. PMID: 30409838; PMCID: PMC6323626.

Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation

Intestinal bacteria profoundly influence bile acid metabolism and host metabolic pathways via the modulation of intestinal farnesoid X receptor (FXR) activity. Reseachers investigated the impact of berberine (BBR), a natural alkaloid, on intestinal bacteria using in vitro and in vivo models. In vivo, short-term BBR exposure led to alterations in intestinal bacteria, notably reducing Clostridium clusters XIVa and IV and their bile salt hydrolase (BSH) activity, resulting in taurocholic acid (TCA) accumulation and subsequent FXR activation. In vitro, BBR exposure directly affected bacterial physiology, composition, and function, particularly reducing BSH-expressing bacteria like Clostridium spp. These findings highlight BBR’s direct influence on bacterial communities, shedding light on its role in bile acid metabolism and FXR signaling modulation, thus providing novel insights into the interplay between intestinal bacteria, nuclear receptor signaling, and xenobiotics.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323626/.
Wang H, Zhang H, Gao Z, Zhang Q, Gu C. The mechanism of berberine alleviating metabolic disorder based on gut microbiome. Front Cell Infect Microbiol. 2022 Aug 25;12:854885. doi: 10.3389/fcimb.2022.854885. PMID: 36093200; PMCID: PMC9452888.

The mechanism of berberine alleviating metabolic disorder based on gut microbiome

As socioeconomic conditions improve, metabolic syndrome garners increasing attention. Research in recent decades highlights the pivotal role of the gut microbiome and its metabolites in metabolic diseases like obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. The bidirectional relationship between gut microbiota and metabolic disorders is well-established, with disruptions in gut microbiota exacerbating metabolic issues. Berberine (BBR), a natural compound, emerges as a significant player in metabolic disorder treatment, with studies demonstrating its ability to ameliorate pathological conditions. BBR’s mechanism of action involves modulation of gut microbiota, influencing its absorption and utilization in the body while altering the microbiota’s structure and function. Our study aims to elucidate BBR’s therapeutic characteristics, focusing on mechanisms such as nitroreductases-producing bacteria expression, intestinal barrier enhancement, inflammation mitigation, and regulation of the bile acid signaling pathway and the bacteria-gut-brain axis, providing insights for metabolic disorder regulation through gut microbiota modulation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9452888/.
Tian Y, Cai J, Gui W, Nichols RG, Koo I, Zhang J, Anitha M, Patterson AD. Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation. Drug Metab Dispos. 2019 Feb;47(2):86-93. doi: 10.1124/dmd.118.083691. Epub 2018 Nov 8. PMID: 30409838; PMCID: PMC6323626.

Berberine Directly Affects the Gut Microbiota to Promote Intestinal Farnesoid X Receptor Activation

Berberine (BBR), a natural plant alkaloid, influences intestinal bacteria, impacting bile acid metabolism and regulating host metabolic pathways like lipid and glucose homeostasis through intestinal farnesoid X receptor (FXR) modulation. In both in vitro and in vivo models, BBR exposure led to alterations in intestinal bacterial communities, particularly reducing Clostridium cluster XIVa and IV and their bile salt hydrolase (BSH) activity, resulting in taurocholic acid (TCA) accumulation. This accumulation correlated with intestinal FXR activation, influencing bile acid, lipid, and glucose metabolism. In vitro studies further demonstrated BBR’s direct physiological and metabolic effects on bacteria, altering their composition and function, notably reducing BSH-expressing bacteria like Clostridium spp. These findings shed light on how BBR directly impacts bacteria to modify bile acid metabolism and activate FXR signaling, revealing insights into the intricate relationship between intestinal bacteria, nuclear receptor signaling, and xenobiotics.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323626/.
Zhang Y, Gu Y, Ren H, Wang S, Zhong H, Zhao X, Ma J, Gu X, Xue Y, Huang S, Yang J, Chen L, Chen G, Qu S, Liang J, Qin L, Huang Q, Peng Y, Li Q, Wang X, Kong P, Hou G, Gao M, Shi Z, Li X, Qiu Y, Zou Y, Yang H, Wang J, Xu G, Lai S, Li J, Ning G, Wang W. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat Commun. 2020 Oct 6;11(1):5015. doi: 10.1038/s41467-020-18414-8. PMID: 33024120; PMCID: PMC7538905.

Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)

In a randomized, double-blind, placebo-controlled trial involving newly diagnosed type 2 diabetes (T2D) patients, interventions targeting the human gut microbiome, such as oral probiotics or berberine (BBR), were explored. Participants received either BBR-alone, probiotics+BBR, probiotics-alone, or placebo for 12 weeks following a one-week gentamycin pretreatment. Results showed that the reduction in glycated hemoglobin was significantly greater in the probiotics+BBR and BBR-alone groups compared to placebo and probiotics-alone groups. BBR treatment led to more gastrointestinal side effects. Metagenomic and metabolomic analyses revealed that BBR’s hypoglycemic effect is mediated by inhibiting DCA biotransformation by Ruminococcus bromii, highlighting a human microbial-related mechanism underlying BBR’s antidiabetic effect in T2D.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538905/.
Hu H, Xu K, Wang K, Zhang F, Bai X. Dissecting the Effect of Berberine on the Intestinal Microbiome in the Weaned Piglets by Metagenomic Sequencing. Front Microbiol. 2022 Apr 7;13:862882. doi: 10.3389/fmicb.2022.862882. PMID: 35464928; PMCID: PMC9021597.

Dissecting the Effect of Berberine on the Intestinal Microbiome in the Weaned Piglets by Metagenomic Sequencing

This study investigated the effects of berberine supplementation on the microbial structure and function in the rectum of weaned piglets. Twelve piglets were divided into control and berberine groups and fed a basal diet with or without 0.1% berberine for 21 days. Metagenomic sequencing analysis revealed differences in microbial composition and function between the two groups. Berberine supplementation led to alterations in microbial diversity, with changes in abundance of specific bacterial species. Analysis also showed variations in carbohydrate-active enzymes and significant shifts in metabolic pathways. These findings suggest that berberine supplementation can modulate the gut microbiome of weaned piglets, potentially offering insights for its application in human and animal health.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021597/.
Cao J, Chen M, Xu R, Guo M. Therapeutic Mechanisms of Berberine to Improve the Intestinal Barrier Function via Modulating Gut Microbiota, TLR4/NF-κ B/MTORC Pathway and Autophagy in Cats. Front Microbiol. 2022 Jul 22;13:961885. doi: 10.3389/fmicb.2022.961885. PMID: 35935245; PMCID: PMC9354406.

Therapeutic Mechanisms of Berberine to Improve the Intestinal Barrier Function via Modulating Gut Microbiota, TLR4/NF-κ B/MTORC Pathway and Autophagy in Cats

Research on inflammatory bowel disease (IBD) has primarily focused on rats and dogs, with limited attention to cats despite significant variations in gut microbiota among species. Traditional Chinese Medicine, particularly berberine, has shown promise in IBD treatment. In this study, we evaluated the therapeutic potential of berberine hydrochloride in cats with IBD. Histological staining and 16S rRNA sequencing revealed that dioctyl sodium sulfosuccinate (DSS) administration disrupted intestinal mucosal structure and altered fecal bacterial composition. Berberine mitigated inflammation by modulating the toll-like receptors 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and activating autophagy, as confirmed by RT-PCR and western blot. Berberine also reduced pro-inflammatory cytokine expression and enhanced antioxidant effects. Notably, berberine restored intestinal barrier function by activating the mammalian target of rapamycin complex (MTORC) while inhibiting autophagy, suggesting a novel mechanism for berberine therapy in IBD cats that warrants further investigation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354406/.
Dehau T, Cherlet M, Croubels S, Van De Vliet M, Goossens E, Van Immerseel F. Berberine-microbiota interplay: orchestrating gut health through modulation of the gut microbiota and metabolic transformation into bioactive metabolites. Front Pharmacol. 2023 Dec 7;14:1281090. doi: 10.3389/fphar.2023.1281090. PMID: 38130410; PMCID: PMC10733463.

Berberine-microbiota interplay: orchestrating gut health through modulation of the gut microbiota and metabolic transformation into bioactive metabolites

Berberine, an isoquinoline alkaloid found in plants, possesses diverse pharmacological properties such as anti-inflammatory and antioxidant effects, despite its low oral bioavailability. While evidence suggests that berberine targets the gut microbiota and is metabolized by it, the specific species involved in its therapeutic effects remain unclear. This study aimed to elucidate the bidirectional interactions between berberine and the broiler chicken gut microbiota, focusing on its regulation of microbiota composition and metabolism, and the metabolization of berberine by gut bacteria and its impact on gut health. Investigating low, middle, and high doses of in-feed berberine, we found that low and middle doses stimulated beneficial bacteria like Lachnospiraceae in the large intestine, while middle and high doses increased villus length in the small intestine. Plasma levels of berberine-derived metabolites correlated positively with villus length, with berberrubine and thalifendine being major metabolites produced by the caecal microbiota. Members of the genus Blautia were identified as key demethylators of berberine into thalifendine, which may stimulate short-chain fatty acid production, suggesting their pivotal role in berberine metabolism and its biological effects.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10733463/.
Fang X, Wu H, Wang X, Lian F, Li M, Miao R, Wei J, Tian J. Modulation of Gut Microbiota and Metabolites by Berberine in Treating Mice With Disturbances in Glucose and Lipid Metabolism. Front Pharmacol. 2022 Jun 3;13:870407. doi: 10.3389/fphar.2022.870407. PMID: 35721198; PMCID: PMC9204213.

Modulation of Gut Microbiota and Metabolites by Berberine in Treating Mice With Disturbances in Glucose and Lipid Metabolism

The study investigated the effects of berberine intervention on glucose and lipid metabolism disturbances in mice using metagenomic and metabolomic analysis. Berberine significantly improved blood glucose and lipid levels, reduced body weight, cholesterol, and triglycerides. It altered gut microbiota structure, enriching specific bacteria, and modulated metabolomic signatures. Negative correlations were observed between reduced fecal metabolites and enriched gut microbiota, suggesting a relationship between microbiota changes and berberine’s efficacy in improving metabolic disturbances.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204213/.
Srivastava K, Cao M, Fidan O, Shi Y, Yang N, Nowak-Wegrzyn A, Miao M, Zhan J, Sampson HA, Li XM. Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature. Front Immunol. 2023 Jul 26;14:1174907. doi: 10.3389/fimmu.2023.1174907. PMID: 37575233; PMCID: PMC10415201.

Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature

In this study, we investigated the potential of an oral Berberine-containing natural medicine combined with boiled peanut oral immunotherapy (BNP) as a treatment for food allergy using a murine model. The results demonstrated that the BNP treatment induced long-term tolerance to peanut allergens, significantly reducing IgE levels, symptom severity, plasma histamine, body temperature, and the number of IgE+ B cells. Analysis of gut microbiota revealed distinct changes associated with treatment response, suggesting a correlation between microbiota alterations and therapeutic outcomes, highlighting the potential of BNP as a promising regimen for food allergy management.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415201/.
Zhao JD, Li Y, Sun M, Yu CJ, Li JY, Wang SH, Yang D, Guo CL, Du X, Zhang WJ, Cheng RD, Diao XC, Fang ZH. Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats. World J Gastroenterol. 2021 Feb 28;27(8):708-724. doi: 10.3748/wjg.v27.i8.708. PMID: 33716449; PMCID: PMC7934002.

Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats

In this study, we investigated the potential of berberine in regulating glucose metabolism in Goto-Kakizaki (GK) rats, a model of type 2 diabetes mellitus (T2DM), by targeting the gut microbiota. Berberine administration significantly improved fasting blood glucose (FBG) levels and glucagon-like peptide-1 (GLP-1) secretion compared to control groups. Additionally, berberine-treated rats exhibited decreased weight and insulin resistance, along with improved pancreatic islet morphology. Analysis of gut microbiota revealed significant alterations in microbial composition, with berberine reducing Bacteroidetes abundance and increasing Allobaculum levels. These findings highlight the potential of berberine in ameliorating metabolic parameters and modulating gut microbiota composition in T2DM rats.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934002/.
Feng R, Shou JW, Zhao ZX, He CY, Ma C, Huang M, Fu J, Tan XS, Li XY, Wen BY, Chen X, Yang XY, Ren G, Lin Y, Chen Y, You XF, Wang Y, Jiang JD. Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep. 2015 Jul 15;5:12155. doi: 10.1038/srep12155. PMID: 26174047; PMCID: PMC4502414.

Transforming berberine into its intestine-absorbable form by the gut microbiota

The gut microbiota’s role in energy-metabolism related diseases and its interaction with orally administered drugs, such as berberine (BBR), are significant. BBR, despite poor solubility, is effectively used in treating metabolic disorders, yet its absorption mechanism remains unclear. We demonstrate that gut microbiota converts BBR into dihydroberberine (dhBBR), enhancing its absorption rate. This conversion, mediated by gut microbiota nitroreductases, leads to dhBBR reverting to BBR in intestinal tissues via oxidation. Antibiotic treatment reducing intestinal bacteria decreases BBR-to-dhBBR conversion, lowering blood BBR levels and diminishing BBR’s therapeutic efficacy. These findings highlight the crucial role of gut microbiota in drug metabolism, shaping drug structure and function, and impacting drug investigation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502414/.
He Q, Dong H, Guo Y, Gong M, Xia Q, Lu F, Wang D. Multi-target regulation of intestinal microbiota by berberine to improve type 2 diabetes mellitus. Front Endocrinol (Lausanne). 2022 Nov 18;13:1074348. doi: 10.3389/fendo.2022.1074348. PMID: 36465656; PMCID: PMC9715767.

Multi-target regulation of intestinal microbiota by berberine to improve type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) and its complications pose significant public health challenges, impacting human life quality. The modulation of intestinal microbiota has emerged as a strategy for managing diabetes. This paper reviews the interplay between T2DM, intestinal microbiota, and the active ingredient berberine (BBR) within the gut microbiota. It explores how alterations in microbiota richness and function disrupt intestinal health, affecting blood glucose, lipids, insulin resistance, and inflammation. Additionally, it highlights BBR’s role in preserving microbiota composition, modulating intestinal metabolites, and regulating immune function. Future research could delve into the multifaceted mechanisms underlying BBR’s therapeutic effects, prov

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