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Am J Chin Med. 2018;46(6):1315-1332. doi: 10.1142/S0192415X18500696. Epub 2018 Sep 5.

Gypenoside UL4-Rich Gynostemma pentaphyllum Extract Exerts a Hepatoprotective Effect on Diet-Induced Nonalcoholic Fatty Liver Disease.

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* Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk 54896, Republic of Korea.
‡ Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Jeonbuk 54907, Republic of Korea.
§ Department of Chemistry, Chonbuk National University, Jeonju, Jeonbuk 54896, Republic of Korea.
¶ Celltrion Chemical Research Institute, Yongin, Gyeonggi 17015, Republic of Korea.
† Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Jeonbuk 54896, Republic of Korea.


Nonalcoholic steatohepatitis (NASH) arises from nonalcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Gynostemma pentaphyllum extract (GPE) is proven to be beneficial for patients suffering from NAFLD. However, the precise mechanism by which GPE confers these benefits remains largely unknown. The purpose of this study was to investigate the underlying mechanism and to determine whether supplementation with the newly discovered GPE gypenoside UL4 mitigates NASH progression. Male c57BL/6 mice were fed a normal chow diet, a methionine choline-deficient (MCD) diet, or an MCD diet supplemented with various doses of UL4-rich GPE for eight weeks. GPE supplementation suppressed oxidative stress induced by the MCD diet by increasing levels of sirtuin 6 and phase 2 anti-oxidant enzymes in mouse liver and HepG2 cells. Additionally, GPE supplementation prevented diet-induced hepatic fat accumulation, hepatocellular injury, inflammation, and fibrosis in mice fed the MCD diet. These results indicate the possible therapeutic potential of dietary supplementation of UL4-rich GPE in preventing the development of fatty liver and its progression to NASH.


Gynostemma pentaphyllum Extract; NAFLD; NASH; Oxidative Stress; Sirtuin 6

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