Hypocholesterolemic effect of hesperetin mediated by inhibition of 3-hydroxy-3-methylglutaryl coenzyme a reductase and acyl coenzyme A : cholesterol acyltransferase in rats fed high-cholesterol diet

Abstract

HMG-CoA reductase and ACAT are associated with regulation of cholesterol metabolism. In present study, the deglycosylated form of hesperidin, hesperetin, was tested both in vivo and in vitro to examine potential differences in mechanism through which hesperetin might affect cholesterol metabolism. When tested in vitro, hesperetin had no inhibitory effect on either HMG-CoA reductase or ACAT. Male rats were fed a high-cholesterol (1%, w/w) diet with or without hesperetin for 42 d to determine hesperetin effects on plasma lipid levels and hepatic cholesterol metabolism. Hesperetin did not change the levels of hepatic lipids, but decreased the concentration of plasma cholesterol (3.24 mmol/L vs. 3.80 mmol/L). Plasma triglyceride level was not different between control and hesperetin-supplemented group (1.12 mol/L vs. 1.29 mmol/L). HMG-CoA reductase and ACAT activities in the liver were significantly reduced by hesperetin supplementation (2005.0 pmole·min-1·mg protein-1 vs. 2487.2 pmole·min-1·mg protein-1 for HMG-CoA reductase, 616.4 pmole·min-1·mg protein-1 vs. 806.2 pmoles/min per mg for ACAT). The most noticeable change by the hesperetin supplementation was a marked decrease in daily excretion of fecal neutral sterols (178.7 mg/d vs. 521.9 mg/d). Results indicate that hesperetin decreased the plasma cholesterol level in rats fed a high-cholesterol diet.