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

Abstract

Alcoholic liver disease (ALD) is a serious worldwide health problem. Ginsenoside Rc is a major active ingredient isolated from Panax ginseng, 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 SIRT6alb–/– mice 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 both in vivo and in vitro. 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.

A Meta-Analysis of Preclinical Studies to Investigate the Effect of Panax ginseng on Alcohol-Associated Liver Disease

“…We then evaluated the titles and abstracts of the remaining records and excluded those that were not relevant to the efficacy of Panax ginseng in ALD, systematic reviews, clinical trials, conference abstracts, books, and theses. After this screening process, we carefully reviewed 37 full-text articles for eligibility and ultimately included 18 studies in our meta-analysis ( Figure 1 ) [ 25 , 26 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ].…”

“… Quality evaluation of included studies [ 25 , 26 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ] according to the SYRCLE’s risk of bias tool. ( A ) Risk of bias graph.…”

“… The effect of Panax ginseng on serological inflammatory markers in [ 25 , 29 , 30 , 31 , 32 , 33 , 34 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Forest plots for comparison ( A ) Serum alanine aminotransferase (ALT) levels.…”

“… Subgroup analysis according to the animal models of alcohol-associated liver disease in [ 25 , 26 , 29 , 30 , 31 , 32 , 33 , 36 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Forest plots for comparison ( A ) Serum alanine aminotransferase (ALT) levels.…”

Effects of various interventions on non-alcoholic fatty liver disease (NAFLD): A systematic review and network meta-analysis

“…PTCs are acquired symbiotic microorganisms that are beneficial to host health when consumed in sufficient quantities ( Pan et al, 2022 ). PTC can treat NAFLD by regulating the composition of the intestinal flora and the production of antibacterial factors, changing the permeability and function of intestinal epithelial cells, modifying endotoxemia, inhibiting inflammation, and regulating the immune system.…”