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

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.

Citrus medicaL. cv Diamante (Rutaceae) peel extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress

“…In mouse models, Citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters and also through direct impact on the vessel wall. Previous data showed that Citrus peel extract causes lowering of CHOL levels by modulating hepatic HMG-CoA levels 34 . Overall, the scientific evidences obtained with fruits from the Citrus genus provide explanations for the beneficial effects of CD extract in hyperlipidaemic and hyperglycaemic disorders.…”

Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables

“…The mechanisms of action are unclear, but hesperetin and=or naringenin have been reported to inhibit estrone sulfatase (Huang et al, 1997) and cytochrome P-450 isoenzymes (Ghosal et al, 1996), to bind to estrogen receptors (Kuiper et al, 1998;Hunter et al, 1999) and to sex hormonebinding globulin (Dechaud et al, 1999), and to act as antioxidants (van Acker et al, 2000;Fuhrman & Aviram, 2001). Furthermore, flavanones have been shown to affect cholesterol metabolism in rats (Bok et al, 1999) and in HepG2 cells (Borradaile et al, 1999), and in a recent study, ingestion of orange juice increased HDL cholesterol levels in hypercholesterolemic human subjects (Kurowska et al, 2000).…”

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

“…Hesperidin and naringin (naringenin-7-Oneohesperidoside) have been reported to reduce plasma and hepatic cholesterol, to inhibit HMG-CoA reductase and Acyl CoA:cholesterol O-acyltransferase in rats, and to reduce net apoB secretion in HepG2 cells (Montforte et al, 1995;Bok et al, 1999;Borradaile et al, 1999). These effects may be of benefit for the prevention of cardiovascular diseases.…”