ORIGINAL PAPER Effect of Cissampelos pareira root extract on isoproterenol-induced cardiac dysfunction Bhulan Kumar Singh • Krishna Kolappa Pillai • Kanchan Kohli • Syed Ehtaishamul Haque Received: 15 May 2011 / Accepted: 6 February 2012 / Published online: 14 March 2012 Ó The Japanese Society of Pharmacognosy and Springer 2012 Abstract The aim of this study was to assess the car- dioprotective effect of Cissampelos pareira root extract on isoproterenol-induced cardiac dysfunction in rats. Male albino Wistar rats were randomly divided into eight groups and received either normal saline (0.5 ml/kg, intraperito- neally), isoproterenol (5 mg/kg, intraperitoneally), C. par- eira (100 and 200 mg/kg, by gavage, respectively) alone, amlodipine (9 mg/kg, by gavage) alone, C. pareira (100 and 200 mg/kg, respectively) ? isoproterenol and amlo- dipine (9 mg/kg) ? isoproterenol, once a day for 30 days, respectively. Isoproterenol-induced cardiac dysfunction was characterized by a significant (P \ 0.001) increase in the heart weigh/body weight ratio, serum calcineurin, nitric oxide, lactate dehydrogenase, and thiobarbituric acid reactive substance levels, as well as a significant decrease in serum-reduced glutathione, cardiac glutathione peroxi- dase, glutathione reductase, and glutathione-S-transferase levels, which were significantly (P \ 0.05 and P \ 0.01) improved by C. pareira treatment. No significant alteration was observed in the group treated with C. pareira alone compared with the control. C. pareira treatment also restored histopathological changes observed in isoprotere- nol-induced rats. Amlodipine is used as standard drug in this study. Thus, these results suggest that the attenuation of isoproterenol-induced cardiac dysfunction by treatment with ethanolic root extract of C. pareira may be due to amelioration of calcineurin activity and free radical for- mation, and by augmentation of antioxidant enzymes activities. Keywords Cissampelos pareira Á Isoproterenol Á Cardiac hypertrophy Á Oxidative stress Á Calcineurin Introduction Chronic b-adrenergic activation in the myocardium is often incriminated in the development of cardiac dysfunction [1]. A correlation between cardiac mass and sympathetic activity was found in young hypertensive humans [2], and long-term administration of norepinephrine led to myo- cardial damage in dogs and rats [3, 4]. The cardiac effect of chronic b-adrenergic stimulation occurred due to an increased oxidative stress resulting from an increased car- diac reactive oxygen species (ROS) production and decreased antioxidant capacity [5–7]. Various studies have reported that angiotensin II, endothelin-1, and a- and b-adrenoreceptors produce cardiac damage through an ROS-dependent pathway [7, 8]. It is well recognized that continuous injections of b-adrenoreceptor agonist isopro- terenol (ISO) causes cardiac dysfunction [9] and oxidative stress [7]. Therefore, it represents a useful experimental model. The use of various herbal remedies and preparations are described throughout human history representing the origin of modern medicine. Many conventional drugs originating from plant sources (e.g., aspirin, digoxin, quinine, mor- phine, etc.) have become mainstays of human pharmaco- therapy [10]. Cissampelos pareira Linn. (Menispermaceae), is popularly known as laghupatha in Ayurveda, and has been extensively used as a medicine for various human B. K. Singh Á K. K. Pillai Á S. E. Haque (&) Department of Pharmacology, Faculty of Pharmacy, Hamdard University, Hamdard Nagar, New Delhi 110062, India e-mail: haquepharm@gmail.com K. Kohli Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi 110062, India 123 J Nat Med (2013) 67:51–60 DOI 10.1007/s11418-012-0643-1