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Abstract Title:

Ginsenoside Rc Modulates SIRT6-NRF2 Interaction to Alleviate Alcoholic Liver Disease.

Abstract Source:

J Agric Food Chem. 2022 Nov 9 ;70(44):14220-14234. Epub 2022 Oct 27. PMID: 36300841

Abstract Author(s):

Zhisen Pan, Jingyi Guo, Kaijia Tang, Yanling Chen, Xun Gong, Yingjian Chen, Yadi Zhong, Xiaoxia Xiao, Siwei Duan, Tianqi Cui, Xiumei Wu, Yanhua Zhong, Xiaoying Yang, Chuangpeng Shen, Yong Gao

Article Affiliation:

Zhisen Pan

Abstract:

Alcoholic liver disease (ALD) is a serious worldwide health problem. Ginsenoside Rc is a major active ingredient isolated from, whose pharmacological effects counteract oxidative stress, inflammation, and lipid accumulation. However, it is still unclear whether ginsenoside Rc might exert beneficial effects on alcohol-induced liver injury. To this aim, mice primary hepatocytes (MPHs) were challenged with alcohol to test ginsenoside Rc's effects on their intracellular alcohol metabolism. C57BL/6J mice or SIRT6mice were chronically fed a diet with added alcohol or given a single gavage of alcohol with or without ginsenoside Rc. Analyses of alcohol metabolism, oxidative stress, inflammation, lipid metabolism, and RNaseq expression were conducted to explore potential targets exploited by ginsenoside Rc to protect against ALD. Our results showed that ginsenoside Rc attenuated alcohol-induced liver injury by regulating oxidative stress, inflammation, and lipid accumulation bothand. Ginsenoside Rc did increase the deacetylase activity of SIRT6, thereby lowering acetylated NRF2 levels, which elevated NRF2's stability, and subsequently exerting an antioxidant effect. In keeping with this, the hepatic knockout of SIRT6 almost abolished the hepatoprotective effects of ginsenoside Rc against ALD. Therefore, our results suggest that ginsenoside Rc attenuated hepatocytes' damage and oxidative stress in ALD by up-regulating the SIRT6/NRF2 pathway. Hence, ginsenoside Rc may be a promising drug to treat or relieve ALD.

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