Plasma and Hepatic Cholesterol and Hepatic Activities of 3-Hydroxy-3-methyl-glutaryl-CoA Reductase and Acyl CoA: Cholesterol Transferase Are Lower in Rats Fed Citrus Peel Extract or a Mixture of Citrus Bioflavonoids

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Abstract
The cholesterol-lowering effects of tangerine peel extract and a mixture of two citrus flavonoids were tested. Male rats were fed a 1 g/100 g high-cholesterol diet for 42 d with supplements of either tangerine-peel extract or a mixture of naringin and hesperidin (0.5 g/100 g) to study the effects of plasma and hepatic lipids, hepatic enzyme activities, and the excretion of fecal neutral sterols. Both the tangerine-peel extract and mixture of two flavonoids significantly lowered the levels (mean ± SE) of plasma (2.44 ± 0.59 and 2.42 ± 0.31 mmol/L, vs. 3.80 ± 0.28 mmol/L, P < 0.05), hepatic cholesterol (0.143 ± 0.017 and 0.131 ± 0.010 mmol/g vs. 0.181 ± 0.003 mmol/g, P < 0.05), and hepatic triglycerides (0.069 ± 0.007 and 0.075 ± 0.006 mmol/g vs. 0.095 ± 0.002 mmol/g, P < 0.05) compared to those of the control. The 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase (1565.0 ± 106.0 pmol · min−1 · mg protein−1 and 1783.0 ± 282 pmol · min−1 · mg protein−1 vs. 2487.0 ± 210.0 pmol · min−1 · mg protein−1, P < 0.05) and acyl CoA: cholesterol O-acyltransferase (ACAT) activities (548.0 ± 65.0 and 615.0 ± 80.0 pmol · min−1 · mg protein−1 vs. 806.0 ± 105.0 pmol · min−1 · mg protein−1, P < 0.05) were significantly lower in the experimental groups than in the control. These supplements also substantially reduced the excretion of fecal neutral sterols compared to the control (211.1 ± 26.7 and 208.2 ± 31.6 mg/d vs. 521.9 ± 53.9 mg/d). The inhibition of HMG-CoA reductase and ACAT activities resulting from the supplementation of either tangerine-peel extract or a combination of its bioflavonoids could account for the decrease in fecal neutral sterol that appears to compensate for the decreased cholesterol biosynthesis in the liver.

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