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

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.