β-sitosterol alleviates atherosclerosis by regulating catalase

Abstract

The aim of this study is to investigate the main active components of Gegen (Puerariae Lobatae Radix) on atherosclerosis and its mechanism of action. Bioinformatics analysis showed that β-sitosterol was the most likely active ingredient to mediate the anti-atherosclerotic effects. In vivo experiments showed that β-sitosterol inhibited plaque formation and platelet activation, and decreased serum total cholesterol (TC) and triglyceride (TG) levels. In vitro experiments showed that β-sitosterol can inhibit lipid deposition and phenotypic transformation of vascular smooth muscle cells (VSMCs). However, knocking down catalase (CAT), the direct target of β-sitosterol, not only promoted lipid deposition and phenotypic transformation of VSMCs, but also activated the PI3K/Akt/mTOR pathway, and the mTOR inhibitor (ink-128) can eliminate the effect of CAT knockdown, suggesting that β-sitosterol may inhibit lipid deposition and phenotypic transformation of VSMCs by activating CAT and silencing the PI3K/Akt/mTOR signaling pathway, thereby alleviating atherosclerosis.

Keywords

• Puerariae lobatae radix
• β-sitosterol
• Atherosclerosis
• Lipid deposition
• VSMCs phenotypic transformation