JPP 2009, 61: 1111–1118 ß 2009 The Authors Received January 30, 2009 Accepted May 20, 2009 DOI 10.1211/jpp/61.08.0016 ISSN 0022-3573 Correspondence: Kalachaveedu Mangathayaru, Sri Ramachandra College of Pharmacy, Sri Ramachandra University, Porur, Chennai-600 116, India. E-mail: kvmanga@yahoo.com Research Paper Modulatory effect of Inula racemosa Hook. f. (Asteraceae) on experimental atherosclerosis in guinea-pigs Kalachaveedu Mangathayaru a , Sarah Kuruvilla b , Kedike Balakrishna d and Jayakothandaramaswamy Venkhatesh c a Sri Ramachandra College of Pharmacy, b Sri Ramachandra Medical College and Research Institute and c Centre for Toxicology and Developmental Research, Sri Ramachandra University, Porur and d Captain Srinivasa Murti Drug Research Institute for Ayurveda and Siddha, Arumbakkam, Chennai, India Abstract Objectives Inula racemosa Hook. f. is indicated for precordial chest pain in Ayurveda. In this study, the effects of a hexane (IrH) and an alcohol extract (IrA) of Inula racemosa on atherosclerosis induced by a high-fat diet in guinea-pigs were investigated. Methods After 30 days on a high-fat diet (guinea-pig pellet diet + 0.2% w/w cholesterol) six animals were killed and evaluated for the onset of early atherosclerotic changes in coronary artery, aorta and major organs. The remaining animals were assigned to 5 groups of six animals each and fed for the following 90 days with a pellet diet + 0.15% w/w cholesterol (positive control) along with 100 mg/kg IrA, 100 mg/kg IrH or 10 mg/kg atorvastatin calcium. The normal control group received only the pellet diet. At the end of experimental period, serum lipid levels, heart and liver antioxidant status, area of lipophilic aortic lesions and histopathology of coronary artery were estimated. Key findings IrA decreased total cholesterol, triglycerides, low-density lipoprotein cholesterol and the atherogenic index, and increased high-density lipoprotein cholesterol compared with the positive control. It scavenged thiobarbituric acid reactive substances and increased reduced glutathione in liver, and enhanced superoxide dismutase and glutathione peroxidase in heart. Aortic lesion area and % bodyweight increase was least in the IrA-treated group. Coronary artery changes due to the high-fat diet were reversed by the extracts. The observed effects are presumably mediated by phenolics in IrA and sesquiterpene lactones in IrH. Conclusions The results demonstrate the anti-atherogenic effect of I. racemosa, thus validating the cardioprotective and anti-obesity claims in traditional medicine. Keywords anti-obesity; antioxidant; atheroprotective; hypolipidaemic; Inula racemosa Introduction The multifactorial aetiopathology and progressive nature of atherosclerosis is well established. [1] Despite lifestyle changes and the use of new pharmacologic approaches to lower plasma cholesterol concentration, cardiovascular disease continues to be the principal cause of death in the US, Europe and much of Asia. [2] Apart from hyperlipidaemia, obesity, diabetes, hypertension and smoking, several emerging risk factors [3] are being identified and the high mortality and morbidity associated with cardiovascular diseases makes it imperative to develop new approaches to their treatment. The polyvalent synergistic action of the different structurally complex phytochemicals from medicinal herbs in the amelioration of several chronic diseases is clinically established and gaining worldwide scientific acceptance. [4] Inula racemosa Hook. f. (Asteraceae), commonly known as ‘pushkarmool’ in India, was first recorded in the ‘Charaka Samhita’ written by the legendary Ayurvedic physician Charaka 2000 years ago. [5] It is described as a medicine for precordial chest pain, cough and dyspnoea. [6] Administered orally for rheumatic pains and inflammatory conditions of the liver, it is also applied externally as a paste or liniment to relieve pain. ‘Pushkara- guggulu’, a traditional remedy for ischaemic and coronary heart disease, [7] is composed of I. racemosa and Commiphora mukul. I. racemosa is known to reverse exercise-induced ST–T changes in electrocardiographs of patients with ischaemic heart disease, and reportedly possesses beta-blocking activity. [8] The root powder enhances prostaglandin-like 1111 Downloaded from https://academic.oup.com/jpp/article/61/8/1111/6135871 by guest on 25 January 2024