© 2009 The Authors Doi: 10.1111/j.1742-7843.2008.00368.x Journal compilation © 2009 Nordic Pharmacological Society. Basic & Clinical Pharmacology & Toxicology, 104, 253–258 Blackwell Publishing Ltd Effects of Rutin on Lipid Profile in Hypercholesterolaemic Rats Amir Ziaee 1,2 , Farzaneh Zamansoltani 2,3 , Marjan Nassiri-Asl 2,4 and Esmail Abbasi 4 1 Department of Endocrinology, Qazvin University of Medical Sciences, Qazvin, Iran, 2 Qazvin Metabolic Disease Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran, 3 Department of Anatomy, Qazvin University of Medical Sciences, Qazvin, Iran, 4 Department of Pharmacology, Qazvin University of Medical Sciences, Qazvin, Iran (Received July 30, 2008; Accepted October 10, 2008) Abstract: Rutin (3, 3′, 4′, 5, 7-pentahydrohyflavone-3-rhamnoglucoside) is a flavonoid of the flavonol type. Rutin is found in many plants and is also an important dietary constituent of food and plant-based beverages. Rutin has several pharmacological properties including antioxidant and cardioprotective activities. Also, it was identified that rutin is the major low-density lipoprotein (LDL) antioxidant compound of mulberry in an in vitro study. The effects of rutin were tested by using it as a supplement in a high-cholesterol diet. Male rats were fed a high-cholesterol diet (1 ml/100 g) for 4 weeks with rutin (10 or 100 mg/kg) or rutin 100 mg/kg and lovastatin supplementation to study the hypocholesterolaemic effects of rutin on plasma lipid levels, hepatic enzyme activity, and liver tissue. Feeding the animals a high-cholesterol diet resulted in marked hypercholesterolaemia and increased the serum level of LDL cholesterol (LDL-C). Rutin (at 100 mg/kg) alone or in combination with lovastatin significantly reduced the levels of total cholesterol, and LDL-C and also markedly decreased liver enzymes and weight in animals with a high-cholesterol diet. Our findings show that 100 mg/kg of rutin alone or with lovastatin supplementation lowered liver weight and enzymes as well as plasma total cholesterol and LDL. The hepatic histopathological results reflect the correlation of rutin and lovastatin combination with both liver weight and the levels of plasma total cholesterol and LDL-C. These results indicate that rutin in combination with lovastatin has increased anti-hypercholesterolaemic effects in an animal model. Cardiovascular disease is now the most common cause of death worldwide. Lipid levels are a metabolic risk factor for cardiovascular disease and abnormalities in plasma lipoprotein classes, and derangements in lipid metabolism rank among the most firmly-established and best-understood risks factors for atherosclerosis [1]. Plasma cholesterol levels are regulated by the absorption of dietary cholesterol, excretion of choles- terol via faecal sterols or bile acids, cholesterol biosynthesis, and removal of cholesterol from circulation. Numerous previous studies have reported on the beneficial effects of hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and acyl-CoA: cholesterol acyltransferase inhibitors of hypercholesterolaemia and atherosclerosis [2,3]. Low- density lipoprotein cholesterol (LDL-C) transports cholesterol from liver to tissues, whereas high-density lipoprotein cholesterol (HDL-C) facilitates the translocation of choles- terol from the peripheral tissues to the liver for catabolism. Therefore, HDL-C has a useful effect in reducing tissue cholesterol and an elevated ratio of HDL-C in serum is suggested together with a decreased level of LDL-C to reduce the risk of cardiovascular diseases [4]. In recent decades, it has been shown that a high-cholesterol level and a high ratio of saturated and monounsaturated to polyunsaturated fatty acids in the blood predisposes patients to vascular diseases, whereas a high dietary intake of vegetables and fruits has the opposite effect [5,6]. Similarly, it was reported that the intake of flavonoids inversely correlates with the plasma total cholesterol and LDL-C concentrations in human beings [7]. Flavonoids are dietary phenolic compounds that are widely distributed in nature and are ubiquitous in plants, fruits, seeds and vegetables. They possess anti-inflammatory, antiviral, antioxidant, hepat- oprotective, antithrombotic, anticancerogenic, and other biological effects [6]. Rutin (3, 3′, 4′, 5, 7-pentahydrohyflavone-3-rhamnoglucoside, fig. 1) is a flavonoid of the flavonol type. Rutin is found in many typical plants such as buckwheat and apples. It is also an important dietary constituent of other foods and plant- based beverages [8]. It was reported that rutin has several pharmacological properties including antioxidant, anticarci- nogenic, cytoprotective, antiplatelet, antithrombic, vasopro- tective and cardioprotective activities [9–14]. Moreover, rutin was found to be a neuroprotective agent and can Author for correspondence: Marjan Nassiri-Asl, Qazvin Metabolic Disease Research Centre, Qazvin, Iran (fax +982813360084, e-mail marjannassiriaslm@gmail.com). Fig. 1. Chemical structure of rutin.