Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterol-regulating enzymes, fecal sterol and tissue morphology in rabbits

Abstract

Background & aims: Hyperlipidemia is a major risk factor for cardiovascular diseases. This study was designed to confirm the hypocholesterolemic role of naringin.

Methods: Male rabbits were fed 0.5% high-cholesterol diet or high-cholesterol diet supplemented with either 0.05% naringin or 0.03% lovastatin for 8 weeks.

Results: The naringin and lovastatin supplements significantly lowered plasma total- and LDL-cholesterol and hepatic lipids levels, while significantly increasing HDL-C/total-C ratio compared to the control group. Hepatic 3-hydroxy-3-methylglutaryl CoA reductase and acyl-CoA: cholesterol acyltransferase activities were significantly higher and lower, respectively, in both supplemented groups than the control group. Total fecal sterol content was significantly increased in lovastatin and especially naringin group. In histopathological analyses, only control group exhibited hepatic lipid droplets, cardiac adipocyte infiltration and slight damage of endothelial lining in aortic wall, but two supplements retarded these atherogenic signs.

Conclusion: It would appear that both naringin and lovastatin contributed to hypocholesterolemic action via down-regulated ACAT activity and higher excretion of fecal sterols in response to high-cholesterol feeding. Also, naringin supplement seemed to preserve tissue morphology from damages induced by high cholesterol diet.

Introduction

Cardiovascular diseases (CVD) remain the leading cause of death in western countries.¹ Hypercholesterolemia is a well-known risk factor for CVD,² and cellular cholesterol homeostasis is very important in the prevention of CVD. The plasma cholesterol level can generally be regulated by the absorption of dietary cholesterol, the excretion of cholesterol via fecal sterol or bile acid, the cholesterol biosynthesis, and the removal of cholesterol from circulation. As such, numerous previous studies have reported on the beneficial effects of HMG-CoA reductase and acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors on hypercholesterolemia and atherosclerosis.3., 4.

In the past decade, substantial progress has been made concerning knowledge of bioactive components in plant foods and their links to health. Human diets of plant origin contain many hundreds of compounds which cannot be considered as nutrients, but appear to play a important role in the maintenance of health. These substances are called nutraceuticals. Special interesting nutraceuticals of food include the polyphenols, phytoestrogens, phytosterols, phytates and polyunsaturated fatty acids, and so on. Especially, the positive role of dietary polyphenol, such as citrus flavonoids in human health is the object of growing scientific interest. Among them, naringin, a naturally occurring bioflavonoid in grapefruits and citrus, has been also reported to possess antimicrobial,⁵ antimutagenic,⁶ anticancer,⁷ and anti-inflammatory⁸ effects. The role of naringin has recently received considerable attention with particular interest in its use as cholesterol-lowering and antiatherogenic agent. The current authors already reported on the hypocholesterolemic effects of naringin mediated by the inhibition of HMG-CoA reductase in rats fed a 1% high-cholesterol diet.9., 10. However, a selection of animal model is important for testing efficacy of nutraceuticals in specific disease-prevention purpose. Accordingly, the present study investigated whether this functional compound, naringin, can suppress the diet-induced hypercholesterolemia as efficiently as lovastatin in rabbits that are very susceptible to develop hypercholesterolemia and atherosclerosis compared to other experimental animals.