Glycyrrhetinic Acid

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]

What is 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.

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.

How does Glycyrrhetinic Acid Work?

Glycyrrhetinic acid is available in alpha and beta forms. The alpha form is present in the 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.

Chemical Structure of Glycyrrhetinic Acid

Research on Glycyrrhetinic Acid

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:

1. Cell studies found that glycyrrhetinic acid promotes fat breakdown and inhibits the production fat cells (adipocytes). [1]
2. In normal-weight subjects, glycyrrhetinic acid administration at 3.5 grams a day for 2 months reduced body fat mass. [2]
3. In healthy women (age range 20-33 years) with normal body mass index (BMI), application of a cream containing 2.5% glycyrrhetinic acidreduced the thickness of subcutaneous thigh fat. [3]
4. In obese animal models, glycyrrhetinic acid supplementation significantly lowered body weight, fat weight, and plasma lipids levels. [4]
5. 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]
6. Glycyrrhetinic acid administration in obese rats promoted weight loss by reducing the levels of SREBP-1, a protein which stimulates fat production. [6]
7. 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:

1. In mice, supplementation of an extract containing glycyrrhetinic acid improved glucose tolerance. [8]
2. In streptozotocin-diabetic rats, administration of 18beta-glycyrrhetinic acid was able to reduce hyperglycemia (high blood sugar levels). [9]
3. 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]
4. A cell study found that glycyrrhetinic acid has protective effects against high blood sugar levels and oxidative stress. [11]
5. In noninsulin-dependent diabetes mouse model, glycyrrhetinic acid supplementation improved tolerance to oral glucose loading 9 weeks after the beginning of test feeding. [12]
6. 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:

1. 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]
2. Glycyrrhetinic acid exerts its antiviral activity by inhibiting the replication of viruses. [17]
3. In murine models of skin and soft tissue infection, 18β-Glycyrrhetinic acid inhibited the survival of Methicillin-resistant Staphylococcus aureus (MRSA). [18-19]
4. In rodents, 18β-Glycyrrhetinic acid significantly attenuated H. pylori-infected gastritis. [20]
5. In cell culture-produced hepatitis C virus, glycyrrhetinic acid reduced viral replication. [21-25]
6. Glycyrrhetinic acid also decreased hepatic and splenic parasite burden in mice infected with protozoa. [26]
7. A cell study also found that glycyrrhetinic acid has significant antiviral activity against rotavirus replication. [27]
8. In mice with burn injuries, glycyrrhetinic acid improved resistance to Pseudomonas aeruginosa wound infection. [28]
9. 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:

1. A study found that glycyrrhetinic acid has cytotoxic and anti-tumor properties. [30]
2. Glycyrrhetinic acid may help prevent breast cancer by inducing programmed cell death (apoptosis) of malignant cells. [31]
3. In human skin cancer cells exposed to ultraviolet radiation, glycyrrhetinic acid inhibited cell replication. [32]
4. 18 β-glycyrrhetinic acid exhibits potent antitumor effects against colorectal cancer by inhibiting proliferation and migration of malignant cells. [33]
5. In nine human cancer cell lines, glycyrrhetinic acid prevented cell replication through apoptosis. [34]
6. In human gastric cancer cells, 18β-glycyrrhetinic acid inhibited migration and invasion of malignant cells. [35]
7. In colon cancer cells, glycyrrhetinic acid induced apoptosis by activating caveolin-1 and Kruppel-like factor-4 proteins. [36]
8. In liver cancer cells, treatment with glycyrrhetinicacid induced apoptosis. [37]
9. Glycyrrhetinic acid exerts its anticancer effects by inhibiting the PTEN/PI3K/Aktsignalling pathway. [38]
10. Glycyrrhetinic acid hydrogel treatment significantly inhibited liver tumor cell growth. [39]
11. Glycyrrhetinic acid exerts its anti-cancer effect by selectively targeting liver cancer cells. [40-41]
12. 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]
13. Administration of glycyrrhetinic acid in tumor-bearing mice recovered body weight and rescued damage of liver and kidney. [43]
14. In human ovarian cancer cells, glycyrrhetinic acid caused cell death by inducing apoptosis. [44]
15. In a mouse model of gastric cell cancer, glycyrrhetinic acidinhibited gastric tumorigenesis through TLR2-accelerated energy metabolism. [45]
16. In leukemia cell line, treatment with glycyrrhetinic acid alone resulted in significant induction of apoptosis and loss of cell viability. [46-47]
17. 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]
18. In non-small cell lung cancer, 18β-Glycyrrhetinic acid treatment suppressed cell proliferation. [50]
19. In mice bearing Krebs-2 carcinoma,glycyrrhetinic acid inhibited tumor growth and reduced tumor cell count. [51]
20. In mice with liver cancer, glycyrrhetinic acidtreatment 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:

1. A study found that glycyrrhetinic acid could prevent drug-induced liver injury and disruption of bile acid metabolism in humans. [53]
2. Pretreatment of liver cells with glycyrrhetinic acid protects against aflatoxin-induced oxidative stress. [54]
3. In mice with liver injury caused by Propionibacterium acnes, glycyrrhetinic acidtreatment 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]
4. 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]
5. In mice, ingestion of glycyrrhetinic acid prevented accumulation of fats in the liver by protecting mitochondria against oxidative stress. [58]
6. In rats, glycyrrhetinic acid treatment reduced endotoxin-induced acute liver injury after partial hepatectomy (surgical removal of a part of the liver). [59]
7. In rats, glycyrrhetinic acid treatment prevented liver injury by inhibiting the production of proteins involved in liver scarring. [60-62]
8. 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:

1. 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]
2. 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]
3. In mice with arthritis, glycyrrhetinic acid treatment reduced symptoms. [66]
4. In mice with heart muscle inflammation (myocarditis), glycyrrhetinic acid treatment reduced the degree of swelling. [67]
5. In contact hypersensitivity model mice, glycyrrhetinic acidadministration resulted in an anti-allergic effect as evidenced by reduced skin inflammation. [68]
6. In mice with spinal cord compression injury, glycyrrhetinic acidadministration reduced secondary inflammatory process. [69-70]
7. In mice with allergic rhinitis, glycyrrhetinic acidtreatment was associated with enhanced antioxidant status and improved immunity activities in the blood and nasal mucosa. [71]
8. In mice with nerve inflammation, glycyrrhetinic acidtreatment inhibited pro-inflammatory mediators in the brain tissue. [72]
9. Glycyrrhetinic acidtreatment also alleviated asthmatic features in mice. [73-74]
10. In rats, glycyrrhetinic acidtreatment ameliorated intestinal inflammation. [75]

Associated Side Effects of Glycyrrhetinic Acid

Glycyrrhetinic acid side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on glycyrrhetinic acid. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of glycyrrhetinic acid. Despite this, it was listed as a side effect associated with glycyrrhetinic acid even though these associated side effects are very uncommon.

Side effects associated with glycyrrhetinic acid may include the following:

• High blood pressure
• Low potassium levels (hypokalemia)
• Inhibition of kidney enzymes

References:

1. Moon MH, Jeong JK, Lee YJ, et al. 18β-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis. BiochemBiophys Res Commun. 2012;420(4):805-10.
2. Armanini D, De palo CB, Mattarello MJ, et al. Effect of licorice on the reduction of body fat mass in healthy subjects. J Endocrinol Invest. 2003;26(7):646-50.
3. Armanini D, Nacamulli D, Francini-pesenti F, Battagin G, Ragazzi E, Fiore C. Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application. Steroids. 2005;70(8):538-42.
4. Park M, Lee JH, Choi JK, et al. 18β-glycyrrhetinic acid attenuates anandamide-induced adiposity and high-fat diet induced obesity. MolNutr Food Res. 2014;58(7):1436-46.
5. Kamisoyama H, Honda K, Tominaga Y, Yokota S, Hasegawa S. Investigation of the anti-obesity action of licorice flavonoid oil in diet-induced obese rats. BiosciBiotechnolBiochem. 2008;72(12):3225-31.
6. Honda K, Kamisoyama H, Tominaga Y, Yokota S, Hasegawa S. The molecular mechanism underlying the reduction in abdominal fat accumulation by licorice flavonoid oil in high fat diet-induced obese rats. AnimSci J. 2009;80(5):562-9.
7. Tominaga Y, Nakagawa K, Mae T, et al. Licorice flavonoid oil reduces total body fat and visceral fat in overweight subjects: A randomized, double-blind, placebo-controlled study. Obes Res ClinPract. 2009;3(3):I-IV.
8. Ko BS, Jang JS, Hong SM, et al. Changes in components, glycyrrhizin and glycyrrhetinic acid, in raw GlycyrrhizauralensisFisch, modify insulin sensitizing and insulinotropic actions. BiosciBiotechnolBiochem. 2007;71(6):1452-61.
9. Kalaiarasi P, Kaviarasan K, Pugalendi KV. Hypolipidemic activity of 18beta-glycyrrhetinic acid on streptozotocin-induced diabetic rats. Eur J Pharmacol. 2009;612(1-3):93-7.
10. Available from https://www.researchgate.net/publication/285774414_Protective_effect_of_18b-glycyrrhetinic_acid_on_lipid_peroxidation_and_antioxidant_enzymes_in_experimental_diabetes
11. Hou S, Zheng F, Li Y, Gao L, Zhang J. The protective effect of glycyrrhizic acid on renal tubular epithelial cell injury induced by high glucose. Int J Mol Sci. 2014;15(9):15026–15043. Published 2014 Aug 26. doi:10.3390/ijms150915026
12. Takii H, Kometani T, Nishimura T, Nakae T, Okada S, Fushiki T. Antidiabetic effect of glycyrrhizin in genetically diabetic KK-Ay mice. Biol Pharm Bull. 2001;24(5):484-7.
13. Sen S, Roy M, Chakraborti AS. Ameliorative effects of glycyrrhizin on streptozotocin-induced diabetes in rats. J Pharm Pharmacol. 2011;63(2):287-96.
14. Li JY, Cao HY, Liu P, Cheng GH, Sun MY. Glycyrrhizic acid in the treatment of liver diseases: literature review. Biomed Res Int. 2014;2014:872139.
15. Pompei R, Flore O, Marccialis MA. Glycyrrhizic acid inhibits virus growth and inactivates virus particles. Nature. 1979;281(5733):689–690.
16. Michaelis M, Geiler J, Naczk P, et al. Glycyrrhizin exerts antioxidativeeffects in H5N1 influenza A virus-infected cells and inhibits virus replication and pro-inflammatory gene expression. PLoS ONE. 2011;6(5)e19705.
17. Ming LJ, Yin AC. Therapeutic effects of glycyrrhizic acid. Nat Prod Commun. 2013;8(3):415-8.
18. Long DR, Mead J, Hendricks JM, Hardy ME, Voyich JM. 18β-Glycyrrhetinic acid inhibits methicillin-resistant Staphylococcus aureus survival and attenuates virulence gene expression. Antimicrob Agents Chemother. 2013;57(1):241–247. doi:10.1128/AAC.01023-12.
19. Oyama K, Kawada-Matsuo M, Oogai Y, Hayashi T, Nakamura N, Komatsuzawa H. Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus. PLoS One. 2016;11(11):e0165831. Published 2016 Nov 7. doi:10.1371/journal.pone.0165831
20. Cao D, Jiang J, You L, et al. The Protective Effects of 18β-Glycyrrhetinic Acid on Helicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils. Biomed Res Int. 2016;2016:4943793. doi:10.1155/2016/4943793
21. Matsumoto Y, Matsuura T, Aoyagi H, Matsuda M, Hmwe SS, Date T, et al. (2013) Antiviral Activity of Glycyrrhizin against Hepatitis C Virus In Vitro. PLoS ONE 8(7): e68992. https://doi.org/10.1371/journal.pone.0068992.
22. Ikeda K. Glycyrrhizin injection therapy prevents hepatocellular carcinogenesis in patients with interferon-resistant active chronic hepatitis C. Hepatology Research. 2007;37(2):S287–S293.
23. Wang H-F, Su H-B, Liu H-L, et al. Clinical research on treatment on several kinds of liver hepatitis with diammoniumglycyrrhizinate. Chinese Journal of Infectious Diseases. 2004;22(2):113–115.
24. Yasui S, Fujiwara K, Tawada A, Fukuda Y, Nakano M, Yokosuka O. Efficacy of intravenous glycyrrhizin in the early stage of acute onset autoimmune hepatitis. Dig Dis Sci. 2011;56(12):3638-47.
25. Cao Y, Tang X-Y, Song F-W. Compare of and beta-Glycyrrhetinic acid alpha-Glycyrrhetinic acid in the treatment of Chronic Hepatitis B. China Journal of Modern Medicine. 2002;12(7):91–92.
26. Available from https://academic.oup.com/jac/article/67/8/1905/748574.
27. Available from https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-9-96.
28. Steinstraesser L, Schubert C, Jacobsen F, Al-benna S. Editorial: glycyrrhizin against multi-resistant bacteria?. J Leukoc Biol. 2010;87(1):7-8.
29. Utsunomiya T, Kobayashi M, Ito M, Pollard RB, Suzuki F. Glycyrrhizin improves the resistance of MAIDS mice to opportunistic infection of Candida albicans through the modulation of MAIDS-associated type 2 T cell responses. Clinical Immunology. 2000;95(2):145–155.
30. Roohbakhsh A, Iranshahy M, Iranshahi M. Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure- Cytotoxic Activity Relationship. Curr Med Chem. 2016;23(5):498-517.
31. Cai Y, Zhao B, Liang Q, Zhang Y, Cai J, Li G. The selective effect of glycyrrhizin and glycyrrhetinic acid on topoisomerase IIα and apoptosis in combination with etoposide on triple negative breast cancer MDA-MB-231 cells. Eur J Pharmacol. 2017;809:87-97.
32. Rossi T, Benassi L, Magnoni C, Ruberto AI, Coppi A, Baggio G. Effects of glycyrrhizin on UVB-irradiated melanoma cells. In Vivo. 2005;19(1):319-22.
33. Wang S, Shen Y, Qiu R, Chen Z, Chen Z, Chen W. 18 β-glycyrrhetinic acid exhibits potent antitumor effects against colorectal cancer via inhibition of cell proliferation and migration. Int J Oncol. 2017;51(2):615-624.
34. Alho DPS, Salvador JAR, Cascante M, Marin S. Synthesis and Antiproliferative Activity of Novel Heterocyclic Glycyrrhetinic Acid Derivatives. Molecules. 2019;24(4).
35. Cai H, Chen X, Zhang J, Wang J. 18β-glycyrrhetinic acid inhibits migration and invasion of human gastric cancer cells via the ROS/PKC-α/ERK pathway. J Nat Med. 2018;72(1):252-259.
36. Chintharlapalli S, Papineni S, Jutooru I, Mcalees A, Safe S. Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator-activated receptor {gamma} agonists in colon cancer cells. Mol Cancer Ther. 2007;6(5):1588-98.
37. Tang ZH, Li T, Chang LL, et al. Glycyrrhetinic Acid triggers a protective autophagy by activation of extracellular regulated protein kinases in hepatocellular carcinoma cells. J Agric Food Chem. 2014;62(49):11910-6.
38. Chang M, Wu M, Li H. Curcumin combined with glycyrrhetinic acid inhibits the development of hepatocellular carcinoma cells by down-regulating the PTEN/PI3K/AKT signalling pathway. Am J Transl Res. 2017;9(12):5567–5575. Published 2017 Dec 15.
39. Chen G, Li J, Cai Y, et al. A Glycyrrhetinic Acid-Modified CurcuminSupramolecular Hydrogel for liver tumor targeting therapy. Sci Rep. 2017;7:44210. Published 2017 Mar 10.
40. Singh H, Kim SJ, Kang DH, et al. Glycyrrhetinic acid as a hepatocyte targeting unit for an anticancer drug delivery system with enhanced cell type selectivity. ChemCommun (Camb). 2018;54(87):12353-12356.
41. Cai Y, Xu Y, Chan HF, Fang X, He C, Chen M. Glycyrrhetinic Acid Mediated Drug Delivery Carriers for Hepatocellular Carcinoma Therapy. Mol Pharm. 2016;13(3):699-709.
42. Available from https://scialert.net/abstract/?doi=pjbs.2011.619.626.
43. Deng QP, Wang MJ, Zeng X, Chen GG, Huang RY. Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma. Cell PhysiolBiochem. 2017;41(4):1383-1392.
44. Haghshenas V, Fakhari S, Mirzaie S, et al. Glycyrrhetinic Acid inhibits cell growth and induces apoptosis in ovarian cancer a2780 cells. Adv Pharm Bull. 2014;4(Suppl 1):437-41.
45. Cao D, Wu Y, Jia Z, et al. 18β-glycyrrhetinic acid inhibited mitochondrial energy metabolism and gastric carcinogenesis through methylation regulated TLR2 signaling pathway. Carcinogenesis. 2018.
46. Hostetler BJ, Uchakina ON, Ban H, Mckallip RJ. Treatment of Hematological Malignancies with Glycyrrhizic Acid. Anticancer Res. 2017;37(3):997-1004.
47. Logemann W, Lauria F, Cudkowicz G, Franceschini J. Antileukæmic activity of glycyrrhetinic acid. Nature. 1960;187(4737):607–608.
48. Hawthorne S, Gallagher S. Effects of glycyrrhetinic acid and liquorice extract on cell proliferation and prostate-specific antigen secretion in LNCaP prostate cancer cells. J Pharm Pharmacol. 2008;60(5):661-6.
49. Thiugnanam S, Xu L, Ramaswamy K, Gnanasekar M. Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP. Oncology Reports. 2008;20(6):1387–1392.
50. Huang RY, Chu YL, Huang QC, et al. 18β-Glycyrrhetinic acid suppresses cell proliferation through inhibiting thromboxane synthase in non-small cell lung cancer. PLoS ONE. 2014;9(4):e93690.
51. Available from https://link.springer.com/article/10.1134/S0026893318020073.
52. Chang M, Wu M, Li H. Antitumor activities of novel glycyrrhetinic acid-modified curcumin-loaded cationic liposomes in vitro and in H22 tumor-bearing mice. Drug Deliv. 2018;25(1):1984-1995.
53. Wang H, Fang ZZ, Meng R, et al. Glycyrrhizin and glycyrrhetinic acid inhibits alpha-naphthylisothiocyanate-induced liver injury and bile acid cycle disruption. Toxicology. 2017;386:133-142.
54. Chan HT, Chan C, Ho JW. Inhibition of glycyrrhizic acid on aflatoxin B1-induced cytotoxicity in hepatoma cells. Toxicology. 2003;188(2-3):211-7.
55. Xiao Y, Xu J, Mao C, et al. 18Beta-glycyrrhetinic acid ameliorates acute Propionibacterium acnes-induced liver injury through inhibition of macrophage inflammatory protein-1alpha. J Biol Chem. 2010;285(2):1128-37.
56. Yang G, Wang L, Yu X, et al. Protective Effect of 18β-Glycyrrhetinic Acid against Triptolide-Induced Hepatotoxicity in Rats. Evid Based Complement Alternat Med. 2017;2017:3470320. doi:10.1155/2017/3470320.
57. Li JY, Cao HY, Liu P, Cheng GH, Sun MY. Glycyrrhizic acid in the treatment of liver diseases: literature review. Biomed Res Int. 2014;2014:872139. doi:10.1155/2014/872139.
58. Korenaga M, Hidaka I, Nishina S, et al. A glycyrrhizin-containing preparation reduces hepatic steatosis induced by hepatitis C virus protein and iron in mice. Liver Int. 2011;31(4):552-60.
59. Tang B, Qiao H, Meng F, Sun X. Glycyrrhizin attenuates endotoxin-induced acute liver injury after partial hepatectomy in rats. Brazilian Journal of Medical and Biological Research. 2007;40(12):1637–1646.
60. Ogiku M, Kono H, Hara M, Tsuchiya M, Fujii H. Glycyrrhizin prevents liver injury by inhibition of high-mobility group box 1 production by kupffer cells after ischemia-reperfusion in rats. Journal of Pharmacology and Experimental Therapeutics. 2011;339(1):93–98.
61. Tu C-T, Li J, Wang F-P, Li L, Wang J-Y, Jiang W. Glycyrrhizin regulates CD4+T cell response during liver fibrogenesis via JNK, ERK and PI3K/AKT pathway. International Immunopharmacology. 2012;14(4):410–421.
62. Zhao J, Wan X-Y, Luo M, Chen T-S, He P. Antifibrotic effects of glycyrrhizin and matrine in vitro and in vivo. Biomedicine and Preventive Nutrition. 2012;2(2):132–137.
63. Wan XY, Luo M, Li XD, He P. Hepatoprotective and anti-hepatocarcinogenic effects of glycyrrhizin and matrine. ChemBiol Interact. 2009;181(1):15-9.
64. Tsukasa Ishida, Yoshiyuki Mizushina, SaoriYagi, et al., “Inhibitory Effects of Glycyrrhetinic Acid on DNA Polymerase and Inflammatory Activities,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 650514, 9 pages, 2012. https://doi.org/10.1155/2012/650514.
65. Mencucci R, Favuzza E, Menchini U. Assessment of the tolerability profile of an ophthalmic solution of 5% glycyrrhizin and copolymer PEG/PPG on healthy volunteers and evaluation of its efficacy in the treatment of moderate to severe blepharitis. ClinOphthalmol. 2013;7:1403-10.
66. Gujral ML, Sareen K, Phukan DP, Amma MK. Antiarthritic activity of glycyrrhizin in adrenalectomised rats. Indian J Med Sci. 1961;15:624-9.
67. Zhang H, Song Y, Zhang Z. Glycyrrhizin administration ameliorates coxsackievirus B3-induced myocarditis in mice. Am J Med Sci. 2012;344(3):206-10.
68. Park HY, Park SH, Yoon HK, Han MJ, Kim DH. Anti-allergic activity of 18beta-glycyrrhetinic acid-3-O-beta-D-glucuronide. Arch Pharm Res. 2004;27(1):57-60.
69. Genovese T, Menegazzi M, Mazzon E, et al. Glycyrrhizin reduces secondary inflammatory process after spinal cord compression injury in mice. Shock. 2009;31(4):367-75.
70. Ni B, Cao Z, Liu Y. Glycyrrhizin protects spinal cord and reduces inflammation in spinal cord ischemia-reperfusion injury. Int J Neurosci. 2013;123(11):745-51.
71. Li XL, Zhou AG, Zhang L, Chen WJ. Antioxidant status and immune activity of glycyrrhizin in allergic rhinitis mice. Int J Mol Sci. 2011;12(2):905-16.
72. Song JH, Lee JW, Shim B, et al. Glycyrrhizin alleviates neuroinflammation and memory deficit induced by systemic lipopolysaccharide treatment in mice. Molecules. 2013;18(12):15788-803.
73. Ram A, Mabalirajan U, Das M, et al. Glycyrrhizin alleviates experimental allergic asthma in mice. IntImmunopharmacol. 2006;6(9):1468-77.
74. Hocaoglu AB, Karaman O, Erge DO, et al. Glycyrrhizin and long-term histopathologic changes in a murine model of asthma. CurrTher Res Clin Exp. 2011;72(6):250-61.
75. Lee Y, Jeong S, Kim W, et al. Glycyrrhizin enhances therapeutic activity of a colon-specific methylprednisolone prodrug against experimental colitis. Dig Dis Sci. 2013;58(5):1226-34.