Cyanidin‐3‐O‐glucoside ameliorates hydrogen peroxide‐induced oxidative stress by regulating HMGCR‐mediated cholesterol anabolism in HEK‐293T cells

Abstract

Cyanidin‐3‐O‐glucoside (C3G), as a typical anthocyanin, exhibits excellent antioxidant effects. This study aimed to demonstrate the role and mechanism of C3G in regulating 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR)‐mediated cholesterol anabolism on H2O2‐induced oxidative stress in HEK‐293T cells. Firstly, the inhibitory effect of C3G on oxidative stress was confirmed by CCK‐8, ROS, and mitochondrial membrane potential (MMP) experiments. Then, proteomics was used to investigate and screen differentially expressed proteins in inhibiting cellular oxidative stress by C3G. HMGCR was screened as a key differentially expressed protein by proteomic analysis. The results verified that C3G could reduce cholesterol levels by inhibiting sterol regulatory element‐binding protein (SREBP2)/HMGCR pathway, increasing ATP, and reducing acetyl‐CoA. Finally, HMGCR had been shown to positively increase ROS accumulation and decrease MMP, which were reversed by intervention of C3G through a series of knockdown and overexpression experiments. In conclusion, the results demonstrated that C3G could inhibit the disorder of cholesterol synthesis in oxidative stress cells by regulating the ROS/SREBP2/HMGCR pathway.