Glycyrrhizin alleviates non-alcoholic steatohepatitis. - GreenMedInfo Summary
Glycyrrhizin alleviates non-alcoholic steatohepatitis via modulating bile acids and meta-inflammation.
Drug Metab Dispos. 2018 Jun 29. Epub 2018 Jun 29. PMID: 29959134
Non-alcoholic steatohepatitis (NASH) is the progressive stage of non-alcoholic fatty liver disease that may ultimately lead to cirrhosis and liver cancer, and there are few therapeutic options for its treatment. Glycyrrhizin (GL), extracted from the traditional Chinese medicine (TCM) liquorice, has potent hepatoprotective effects in both preclinical animal models and in humans. However, little is known about its effects and mechanisms in treating NASH. To explore the effects of GL on NASH, GL or its active metabolite glycyrrhetinic acid (GA), was administered to mice treated with a methionine-choline-deficient (MCD) diet-induced NASH model, and histological and biochemical analyses used to measure the degree of lipid disruption, liver inflammation and fibrosis. GL significantly improved MCD diet-induced hepatic steatosis, inflammation and fibrosis, and inhibited activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. GL significantly attenuated serum bile acids accumulation in MCD diet-fed mice partially by restoring inflammation-mediated hepatic farnesoid X receptor (FXR) inhibition. In Raw 264.7 macrophage cells, both GL and GA inhibited deoxycholic acid-induced NLRP3 inflammasome-associated inflammation. Notably, both intraperitoneal injection of GL's active metabolite GA, and oral administration of GL, prevented NASH in mice, indicating that GL may attenuate NASH via its active metabolite GA. These results reveal that GL, via restoring bile acids homeostasis and inhibiting inflammatory injury, can be a therapeutic option for treatment of NASH.