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

HMG-CoA reductase and ACAT are associated with regulation of cholesterol me tabolism. In present study, the deglycosylated form of hesperidin, hesperet in, was tested both in vivo and in vitro to examine potential differences i n mechanism through which hesperetin might affect cholesterol metabolism. W hen tested ill vitro, hesperetin had no inhibitory effect on either HMG-CoA reductase or ACAT. Male rats were fed a high-cholesterol (1%, w/w) diet wi th 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 ch olesterol (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 sign ificantly reduced by hesperetin supplementation (2005.0 pmole.min(-1) mg pr oteim(-1) vs. 2487.2 pmole.min(-1) mg protein`' for HMG-CoA reductase, 616. 4 pmole.min(-1) mg proteim(-1) vs. 806.2 pmoles/min per mg for ACAT). The m ost noticeble change by the hesperetin supplementation was a marked decreas e 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. (C) 1999 Elsevier Science Inc.