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

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 weeks. 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.