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Glycyrrhetinic Acid

Glycyrrhetinic acid, also known as glycyrrhizic acid, is one of the main bioactive compounds of licorice that is widely used in various foods as a natural sweetener. It’s also used to impart a flavor in a wide array of cosmetic and personal care products. As a therapeutic agent, glycyrrhetinic acid is also the main ingredient in various health formulations because of its anti-inflammatory, anti-ulcer, anti-allergic, anti-tumor, anti-diabetic, antioxidant, and liver-protective properties.

Overall Health Benefits of Glycyrrhetinic Acid

  • Promotes Weight Loss [1-7]
  • Controls Blood Sugar Levels [8-13]
  • Fights Infection [14-29]
  • Fights Cancer [31-52]
  • Protects the Liver [53-63]
  • Combats Inflammatory Conditions [64-75]

How does Glycyrrhetinic Acid Works?

Glycyrrhetinic acid is available in the alpha and beta forms. The alpha form is present in highest amounts in the stomach and liver, and it is thought that the dominance of glycyrrhetinic acid in these areas can produce anti-inflammatory effect. On the other hand, beta glycyrrhetinic acid exerts its beneficial effects by reducing lipid peroxidation and increasing antioxidant activity. Glycyrrhetinic acid also works to lower inflammatory substances and free radical levels in the body. Moreover, Glycyrrhetinic acid increases the levels of substances that stimulate gastric acid and mucus secretion in the digestive system.

Proven Health Benefits of Glycyrrhetinic Acid

The medical use of glycyrrhetinic acid dates back to ancient Egyptian times where they used licorice root as a cure-all concoction. This herb also became an important treatment strategy in Chinese medicine. Interestingly, modern clinical trials found that the glycyrrhetinic acid in licorice exerts potent therapeutic effect in a wide array of medical conditions.

Promotes Weight Loss

Glycyrrhetinic acid may benefit people who are overweight or obese. Studies show that this powerful compound has the ability to promote fat loss:

  • Cell studies found that glycyrrhetinic acid promotes fat breakdown and inhibits the production fat cells (adipocytes). [1]
  • In normal-weight subjects, glycyrrhetinic acid administration at 3.5 grams a day for 2 months reduced body fat mass. [2]
  • In healthy women (age range 20-33 years) with normal body mass index (BMI), application of a cream containing 2.5% glycyrrhetinic acid reduced the thickness of subcutaneous thigh fat. [3]
  • In obese animal models, glycyrrhetinic acid supplementation significantly lowered body weight, fat weight, and plasma lipids levels. [4]
  • In diet-induced obese rats, glycyrrhetinic acid supplementation decreased the weight of abdominal adipose tissue by regulating enzymatic activity involved in deposition and breakdown of fats. [5]
  • Glycyrrhetinic acid administration in obese rats promoted weight loss by reducing the levels of SREBP-1, a protein which stimulates fat production. [6]
  • In moderately overweight men and women, glycyrrhetinic acid administration at 900 mg/day for 8 weeks significantly decreased visceral fat area, body weight, and BMI. [7]

Controls Blood Sugar Levels

There is also increasing evidence that supports the anti-diabetic effect of glycyrrhetinic acid:

In mice, supplementation of an extract containing glycyrrhetinic acid improved glucose tolerance. [8]

  • In streptozotocin-diabetic rats, administration of 18beta-glycyrrhetinic acid was able to reduce hyperglycemia (high blood sugar levels). [9]
  • In adult male rats, 18beta-glycyrrhetinic acid administration was associated with increased antioxidants status and decreased lipid peroxidation, which reflects protective effect against diabetes risk. [10]
  • A cell study found that glycyrrhetinic acid has protective effects against high blood sugar levels and oxidative stress. [11]
  • In noninsulin-dependent diabetes mouse model, glycyrrhetinic acid supplementation improved tolerance to oral glucose loading 9 weeks after the beginning of test feeding. [12]
  • In rats with streptozotocin-induced diabetes, glycyrrhetinic acid treated hyperglycemia, hyperlipidemia and associated oxidative stress, suggesting that it may be a potential therapeutic agent for diabetes treatment. [13]

Fights Infection

Studies show that glycyrrhetinic acid also has immune-boosting properties that can help fight infection:

  • The antiviral activity of glycyrrhetinic acid can fight a wide array of virus such as vesicular stomatitis virus, influenza virus, herpes simplex virus, Newcastle disease virus, and vaccinia virus. [14-16]
  • Glycyrrhetinic acid exerts its antiviral activity by inhibiting the replication of viruses. [17]
  • In murine models of skin and soft tissue infection, 18β-Glycyrrhetinic acid inhibited the survival of Methicillin-resistant Staphylococcus aureus (MRSA). [18-19]
  • In rodents, 18β-Glycyrrhetinic acid significantly attenuated H. pylori-infected gastritis. [20]
  • In cell culture-produced hepatitis C virus, glycyrrhetinic acid reduced viral replication. [21-25]
  • Glycyrrhetinic acid also decreased hepatic and splenic parasite burden in mice infected with protozoa. [26]
  • A cell study also found that glycyrrhetinic acid has significant antiviral activity against rotavirus replication. [27]
  • In mice with burn injuries, glycyrrhetinic acid improved resistance to Pseudomonas aeruginosa wound infection. [28]
  • Glycyrrhetinic acid improved the resistance of mice to opportunistic infection of Candida albicans through modulation of T cell responses. [29]

Fights Cancer

Numerous studies also show that glycyrrhetinic acid has potent anti-cancer properties:

  • A study found that glycyrrhetinic acid has cytotoxic and anti-tumor properties. [30]
  • Glycyrrhetinic acid may help prevent breast cancer by inducing programmed cell death (apoptosis) of malignant cells. [31]
  • In human skin cancer cells exposed to ultraviolet radiation, glycyrrhetinic acid inhibited cell replication. [32]
  • 18 β-glycyrrhetinic acid exhibits potent antitumor effects against colorectal cancer by inhibiting proliferation and migration of malignant cells. [33]
  • In nine human cancer cell lines, glycyrrhetinic acid prevented cell replication through apoptosis. [34]
  • In human gastric cancer cells, 18β-glycyrrhetinic acid inhibited migration and invasion of malignant cells. [35]
  • In colon cancer cells, glycyrrhetinic acid induced apoptosis by activating caveolin-1 and Kruppel-like factor-4 proteins. [36]
  • In liver cancer cells, treatment with glycyrrhetinic acid induced apoptosis. [37]
  • Glycyrrhetinic acid exerts its anticancer effects by inhibiting the PTEN/PI3K/Akt signalling pathway. [38]
  • Glycyrrhetinic acid hydrogel treatment significantly inhibited liver tumor cell growth. [39]
  • Glycyrrhetinic acid exerts its anti-cancer effect by selectively targeting liver cancer cells. [40-41]
  • In hamsters, oral administration of glycyrrhetinic acid at a dose of 45 mg/kg body weight resulted in complete prevention of oral tumor formation and restoration of detoxification enzymes. [42]
  • Administration of glycyrrhetinic acid in tumor-bearing mice recovered body weight and rescued damage of liver and kidney. [43]
  • In human ovarian cancer cells, glycyrrhetinic acid caused cell death by inducing apoptosis. [44]
  • In a mouse model of gastric cell cancer, glycyrrhetinic acid inhibited gastric tumorigenesis through TLR2-accelerated energy metabolism. [45]
  • In leukemia cell line, treatment with glycyrrhetinic acid alone resulted in significant induction of apoptosis and loss of cell viability. [46-47]
  • In prostate cancer cell line, treatment with glycyrrhetinic acid reduced the rate of cell proliferation and production of prostate‐specific antigen (marker of prostate cancer). [48-49]
  • In non-small cell lung cancer, 18β-Glycyrrhetinic acid treatment suppressed cell proliferation. [50]
  • In mice bearing Krebs-2 carcinoma, glycyrrhetinic acid inhibited tumor growth and reduced tumor cell count. [51]
  • In mice with liver cancer, glycyrrhetinic acid treatment resulted in inhibition of tumor growth, reduction of tumor microvascular density, reduction of inflammatory markers, and improvement in the production of immune system cells. [52]

Protects the Liver

Evidence suggests that glycyrrhetinic acid has a protective effect on liver injury through its anti-inflammatory activity:

  • A study found that glycyrrhetinic acid could prevent drug-induced liver injury and disruption of bile acid metabolism in humans. [53]
  • Pretreatment of liver cells with glycyrrhetinic acid protects against aflatoxin-induced oxidative stress. [54]
  • In mice with liver injury caused by Propionibacterium acnes, glycyrrhetinic acid treatment inhibited the activation and proliferation of liver-infiltrating CD4(+) T cells and reduced the production of inflammatory substances such as interferon-gamma and tumor necrosis factor-alpha. [55]
  • In rats, low-dose glycyrrhetinic acid (50 mg/kg) exhibited a protective effect against Triptolide-induced liver injury through its anti-inflammatory, antioxidant, and antiapoptotic properties. [56-57]
  • In mice, ingestion of glycyrrhetinic acid prevented accumulation of fats in the liver by protecting mitochondria against oxidative stress. [58]
  • In rats, glycyrrhetinic acid treatment reduced endotoxin-induced acute liver injury after partial hepatectomy (surgical removal of a part of the liver). [59]
  • In rats, glycyrrhetinic acid treatment prevented liver injury by inhibiting the production of proteins involved in liver scarring. [60-62]
  • In mice, glycyrrhetinic acid attenuated acetaminophen-induced liver injury. [63]

Combats Inflammatory Conditions

Numerous studies suggest that the potent anti-inflammatory properties of glycyrrhetinic acid allow it to treat a multitude of inflammatory conditions:

  • A study found that glycyrrhetinic acid contains substances that are very effective in suppressing inflammatory markers such as nuclear factor-κB (NF-κB) and 12-O-tetradecanoylphorbol-13-acetate. [64]
  • In healthy volunteers and in patients with chronic moderate/severe blepharitis (eyelid inflammation), administration of glycyrrhetinic acid ophthalmic solution showed good clinical anti-inflammatory activity. [65]
  • In mice with arthritis, glycyrrhetinic acid treatment reduced symptoms. [66]
  • In mice with heart muscle inflammation (myocarditis), glycyrrhetinic acid treatment reduced the degree of swelling. [67]
  • In contact hypersensitivity model mice, glycyrrhetinic acid administration resulted in an anti-allergic effect as evidenced by reduced skin inflammation. [68]
  • In mice with spinal cord compression injury, glycyrrhetinic acid administration reduced secondary inflammatory process. [69-70]
  • In mice with allergic rhinitis, glycyrrhetinic acid treatment was associated with enhanced antioxidant status and improved immunity activities in the blood and nasal mucosa. [71]
  • In mice with nerve inflammation, glycyrrhetinic acid treatment inhibited pro-inflammatory mediators in the brain tissue. [72]
  • Glycyrrhetinic acid treatment also alleviated asthmatic features in mice. [73-74]
  • In rats, glycyrrhetinic acid treatment ameliorated intestinal inflammation. [75]

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