Prevention of free fatty acid–induced hepatic lipotoxicity by 18β-glycyrrhetinic acid through lysosomal and mitochondrial pathways

• DOI: 10.1002/hep.22239
• Publication Date: 2008-02-07T15:16:51Z
• Authors: Xudong Wu; Luyong Zhang; Emily Gurley; Elaine Studer; Jing Shang; Tao Wang; Cuifen Wang; Ming Yan; Zhenzhou Jiang; Phillip B. Hylemon; Arun J. Sanyal; William M. Pandak; Huiping Zhou
• Keywords: Lipotoxicity; Steatosis; Hepatic stellate cell

Nonalcoholic fatty liver disease (NAFLD) is the most common and affects millions of people worldwide. Despite increasing prevalence NAFLD, exact molecular/cellular mechanisms remain obscure effective therapeutic strategies are still limited. It well-accepted that free acid (FFA)-induced lipotoxicity plays a pivotal role in pathogenesis NAFLD. Inhibition FFA-associated hepatic toxicity represents potential strategy. Glycyrrhizin (GL), major bioactive component licorice root extract, has variety pharmacological properties including anti-inflammatory, antioxidant, immune-modulating activities. GL been used to treat hepatitis reduce inflammation injury; however, mechanism underlying antihepatic injury property poorly understood. In this report, we provide evidence 18 β-glycyrrhetinic (GA), biologically active metabolite GL, prevented FFA-induced lipid accumulation cell apoptosis vitro HepG2 (human line) NAFLD models. GA also high fat diet (HFD)-induced vivo rat was found stabilize lysosomal membranes, inhibit cathepsin B expression enzyme activity, mitochondrial cytochrome c release, oxidative stress. These characteristics may represent cellular mechanisms, which account for its protective effects on FFA/HFD-induced lipotoxicity. Conclusion: significantly reduced by stabilizing integrity lysosomes mitochondria inhibiting activity.