Cyanidin‐3‐O‐glucoside improves non‐alcoholic fatty liver disease by promoting PINK1‐mediated mitophagy in mice

Published on Aug 1, 2020in British Journal of Pharmacology7.73
· DOI :10.1111/BPH.15083
Xinwei Li23
Estimated H-index: 23
(JLU: Jilin University),
Zhen Shi10
Estimated H-index: 10
(JLU: Jilin University)
+ 12 AuthorsGuowen Liu27
Estimated H-index: 27
(JLU: Jilin University)
BACKGROUND AND PURPOSE: Identifying safe and effective compounds that target to mitophagy to eliminate impaired mitochondria may be an attractive therapeutic strategy for NAFLD. Here, we investigated the effects of cyanidin-3-O-glucoside (C3G) on NAFLD and the underlying mechanism. EXPERIMENTAL APPROACH: NAFLD was induced by a high-fat diet (HFD) for 16 weeks. C3G was administered during the last 4 weeks. In vivo, recombinant adenoviruses and AAV8 were used for overexpression and knockdown of PTEN-induced kinase 1 (PINK1), respectively. AML-12 and HepG2 cells were used for the mechanism study. KEY RESULTS: C3G administration suppressed hepatic oxidative stress, NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, steatosis and improve systemic glucose metabolism in mice with NAFLD. These effects of C3G also observed in palmitic acid-treated AML-12 cells and hepatocytes from NAFLD patients. Mechanistic investigations revealed that C3G increased PTEN-induced kinase 1 (PINK1)/Parkin expression and mitochondrial localization, promotes PINK1-mediated mitophagy to clear damaged mitochondria. Knockdown of hepatic PINK1 abolished the mitophagy-inducing effect of C3G, which blunted the beneficial effects of C3G on oxidative stress, NLRP3 inflammasome activation, hepatic steatosis and glucose metabolism. CONCLUSION AND IMPLICATIONS: These results demonstrate that PINK1-mediated mitophagy plays an essential role in the ability of C3G to alleviate NAFLD and suggest that C3G may be a potential drug candidate for NAFLD treatment.
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