Cholesterol-Lowering Activity of Naringenin via Inhibition of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase and Acyl Coenzyme A:Cholesterol Acyltransferase in Rats

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Abstract
The effects of dietary supplementation of a citrus bioflavonoid, naringenin, on the cholesterol metabolism were studied. For 42 days male rats were fed a 1% (wt/wt) high-cholesterol diet with or without a naringenin supplementation (0.1%, wt/wt) to study its effect on plasma lipid levels, hepatic lipid contents, activities of hepatic acyl coenzyme A:cholesterol O-acyltransferase (ACAT) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and the excretion of fecal neutral sterols. Naringenin did not significantly alter the concentration of plasma triglycerides, but lowered the plasma cholesterol (3.80 vs. 3.12 mmol/l) concentration and the hepatic cholesterol content (70.3 vs. 54.0 mg/g) significantly (p < 0.05) compared to those of the controls. HMG-CoA reductase (1,879.0 vs. 1,715.0 pmol/min/mg) and ACAT activities (806.0 vs. 563.0 pmol/min/mg) were significantly lower in the naringenin-supplemented group than in controls. Naringenin supplementation caused a marked decrease in the excretion of fecal neutral sterols (242.9 mg/day) compared to the controls (521.9 mg/day). These results show that naringenin lowers the plasma and hepatic cholesterol concentrations by suppressing HMG-CoA reductase and ACAT in rats fed a high-cholesterol diet.