Indian Journal of Biochemistry & Biophysics Vol. 48, February 2011, pp. 22-28 Effect of Inula racemosa root extract on cardiac function and oxidative stress against isoproterenol-induced myocardial infarction Shreesh Ojha, Saurabh Bharti, Ashok K Sharma, Neha Rani, Jagriti Bhatia, Santosh Kumari a and Dharamvir Singh Arya* Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India a Division of Plant Physiology, Indian Agricultural Research Institute, New Delhi 110017, India Received 07 July 2010; revised 04 January 2011 The cardioprotective potential of Inula racemosa root hydroalcoholic extract against isoproterenol-induced myocardial infarction was investigated in rats. The rats treated with isoproterenol (85 mg/kg, s.c.) exhibited myocardial infarction, as evidenced by significant (P<0.05) decrease in mean arterial pressure, heart rate, contractility, relaxation along with increased left ventricular end diastolic pressure, as well as decreased endogenous myocardial enzymatic and non-enzymatic antioxidants. Isoproterenol also significantly (P<0.05) induced lipid peroxidation and increased leakage of myocyte injury marker enzymes. Pretreatment with I. racemosa extract (50, 100 or 200 mg/kg per day, p.o.) for 21 consecutive days, followed by isoproterenol injections on days 19 th and 20 th significantly (P<0.05) improved cardiac function by increasing the heart rate, mean arterial pressure, contractility and relaxation along with decreasing left ventricular end diastolic pressure. Pretreatment with I. racemosa also significantly (P<0.05) restored the reduced form of glutathione and endogenous antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase from the heart, which were depleted after isoproterenol administration. In addition to restoration of antioxidants, I. racemosa significantly (P<0.05) inhibited lipid peroxidation and prevented the leakage of myocytes specific marker enzymes creatine phosphokinase-MB and lactate dehydrogenase from the heart. Thus, it is concluded that I. racemosa protects heart from isoproterenol-induced myocardial injury by reducing oxidative stress and modulating hemodynamic and ventricular functions of the heart. Present study findings demonstrate the cardioprotective effect of I. racemosa and support the pharmacological relevance of its use and cardioprotection mechanism in ischemic heart disease as well as substantiate its traditional claim. Keywords: Antioxidant, Cardiac function, Cardioprotective potential, Inula racemosa, Isoproterenol, Oxidative stress, Pushkarmool, Ventricular function. Myocardial infarction (MI), the common presentation of ischemic heart disease is on rise worldwide in both men and women and is a leading cause of death and disability 1 . It is an acute condition of the necrosis in the myocardium which occurs as a result of imbalance between coronary blood supply and myocardial demand. Although, modern drugs are effective in treating ischemic- reperfusion condition, but there is still a need to develop newer therapeutic agents 2 . Growing evidences suggest that medicinal plants render resistance to heart from ischemic injury and protect from the deteriorated hemodynamic and ventricular function, a common accompaniment of ischemic myocardium 3-6 . The identification of such medicinal plants may be useful as a phytotherapeutic agent or adjuvant to prevent or limit myocardial ischemic injury and associated functional impairment. Therefore, it is desirable to explore such agents/therapies that prevent or attenuate ischemic injury in rat model of isoproterenol (ISO)-induced myocardial necrosis. Isoproterenol, a synthetic catecholamine and a potent β-adrenergic agonist produces myocardial necrosis in rats comparable to those taking place in human AMI 7,8 . There are many mechanisms of ISO- induced myocardial infarction such as activation of β 1 and β 2 -adrenoceptors, which leads to positive inotropic and chronotropic effects, and production of free radicals thru auto-oxidation of catecholamines 7-9 . Catecholamines play an important role in myocardial —————— *Corresponding author E-mail: dsarya16@hotmail.com Tel: +91-11-26594266 Fax: +91-11-26594266 Abbreviations: AMI, acute myocardial infarction; CAT, catalase; CK-MB, creatine phosphokinase-MB; GPx, glutathione peroxidise; GSH, reduced glutathione; HR, heart rate; IR, Inula racemosa; ISO, isoproterenol; LDH, lactate dehydrogenase; LVEDP, left ventricular end diastolic pressure; (+)LVdP/dt, peak positive pressure development; (-)LVdP/dt, peak negative pressure decline; MAP, mean arterial pressure; MI, myocardial infarction; ROS, reactive oxygen species; SOD, superoxide dismutase; TLC, thin layer chromatography; TBARS, thiobarbituric acid reactive substances.