Cholesterol-reducing effect of ergosterol is modulated via inhibition of cholesterol absorption and promotion of cholesterol excretion

Abstract

Abstract Ergosterol is the common sterol found in edible mushrooms. This study investigated the cholesterol-reducing effect of ergosterol and its related potential mechanism in Sprague-Dawley rats. Thirty-two male rats were divided into four groups fed either a basic diet (NG) or one of three experimental diets, namely high-cholesterol diet (HC), and the two HC diets containing 0.5% ergosterol (EL) and 1.5% ergosterol (EH), respectively, for 8\u202fweeks. Results demonstrated that feeding EL and EH diets decreased serum total cholesterol (TC) by 19.4–21.6%, low density lipoproptein cholesterol (LDL-C) by 42.0–42.6%, and TC/HDL-C ratio by 7.1–10.5%. This was accompanied by 46.8–53.2% reduction in liver cholesterol and 51.0–59.3% increase in fecal cholesterol excretion with up-regulation on gene expression of liver sterol regulatory element-binding protein 2 (SREBP-2), low-density lipoprotein receptor (LDL-R) and Hydroxy-3-Methylglutaryl-Coenzyme A Reductase (HMG-CoR). Results from micelles formation assay in vitro clearly demonstrated that ergosterol could significantly inhibit the entry of cholesterol into micelles. Therefore, the cholesterol-reducing effect of ergosterol was regulated by suppressing intestine cholesterol absorption and promoting the excretion of fecal cholesterol via modulating the expression of hepatic cholesterol-related genes.