Available online at www.scholarsresearchlibrary.com Scholars Research Library Der Pharmacia Lettre, 2015, 7 (10):57-67 (http://scholarsresearchlibrary.com/archive.html) ISSN 0975-5071 USA CODEN: DPLEB4 57 Scholar Research Library Regulatory efficacy of scopoletin, a biocoumarin on aortic oxido lipidemic stress through antioxidant potency as well as suppression of mRNA expression of inos gene in hypercholesterolemic rats C. Shanmuga Sundaram 1 , U. S. Mahadeva Rao 2 and Nordin Simbak 2 1 Department of Biochemistry, Prof. Dhanapalan College of Arts and Science, Chennai, India 2 Faculty of Medicine and Health Science, Universiti Sultan Zainal Abidin, Kuala Terengganu, Malaysia _____________________________________________________________________________________________ ABSTRACT Preceding work in our laboratory has revealed that scopoletin, one of the main bioactive coumarin from fruits of Morinda citrifolia, exerts anti-diabetic activity in in vitro partly by averting α glucosidase and α amylase action. However, its aorto/vaso protective impact-based research is still incomprehensible. The present study looks into the regulatory efficacy of scopoletin on aortic lipid profile, radical scavenging status, endothelial factors and aortic morphology in dyslipidemic rats. Rats fed with normal diet serve as control [Group (G) 1], rats fed with cholesterol- enriched diet (CED) (4 % cholesterol and 1 % cholic acid) for 45 days (G2), rats fed with CED for 45 days + scopoletin (10 mg/kg, body weight/day orally) for the last 30 days (G3) and scopoletin alone rats (G4). Blood and aortic tissue were taken immediately and used for various biochemical, histological and molecular analyses. A pronounced increase in the levels of aortic lipid profile, lipid peroxidation along with substantial suppression in the activities of aortic antioxidant and endothelial factor was observed in G2. The mRNA expression levels of iNOS gene were significantly up-regulated in aortic tissue of G2. On treatment with scopoletin, all the levels were reverted to near normalcy G3. Morphology of aorta in G2 indicated numerous foam cells with intimal changes, whereas the aorta of G3 exhibited fewer foam cells with normal intima. These results support that scopoletin expressively represses the aortic oxido-lipidemic stress and thereby upholding normal morphology of the aorta, and thus minimizing the peril of CVD. Keywords: Scopoletin; Endothelial factor; Cholesterol; Radical scavenging; mRNA expression. _____________________________________________________________________________________________ INTRODUCTION Atherosclerosis is a process that leads to the narrowing or complete occlusion of the arterial lumen myocardial infarction, stroke, or peripheral vascular disease. Atherogenesis is the process of development of atherosclerotic plaques. The key early event in atherosclerosis is damage to the endothelium. The endothelium loses its cell- repellent quality and admits inflammatory cells into the vascular wall. It also becomes more permeable to lipoproteins which deposit in the intima. This may be caused by excess of lipoproteins, hypertension and diabetes or by components of cigarette smoke. Initially the damage is more functional than structural; later, there is structural damage or a complete destruction of endothelial cells [1–3]. Hypercholesterolemia stimulates atherogenesis by damaging the endothelial wall [4] owing to a sizable production of free radicals [5]. Too much production of free radicals outstrips endogenous free radical scavenging mechanisms