Pharmacological Research 103 (2016) 227–235 Contents lists available at ScienceDirect Pharmacological Research journal homepage: www.elsevier.com/locate/yphrs -Asarone modulate adipokines and attenuates high fat diet-induced metabolic abnormalities in Wistar rats Malesh M. Thakare ∗ , Sanjay J. Surana Department of Pharmacology, RC Patel Institute of Pharmaceutical Education and Research, Shirpur 425 405, Dhule, Maharashtra, India a r t i c l e i n f o Article history: Received 19 April 2015 Received in revised form 1 December 2015 Accepted 1 December 2015 Available online 7 December 2015 Keywords: -Asarone Adipokines High fat diet Obesity Diabetes Dyslipidemia a b s t r a c t Here we investigated the effect of -asarone on food preference and its therapeutic potential against high fat diet (HFD) induced obesity in rats. In food preference study, free access to HFD was given only for 4 h in addition to standard laboratory chow in rats and the preferential intake between chow and HFD was measured. For obesity induction, HFD was administered for 12 weeks and the HFD fed rats were treated with -asarone in the last 4 weeks, starting from 9th week onwards. Food intake, body weight was measured biweekly. Glucose tolerance and the levels of glucose, lipids, free fatty acids, leptin, and adiponectin were assessed. HFD fed rats showed progressive increase in body weight and developed glucose intolerance and dyslipidemia. In addition, they showed increased adiposity and the disturbed pattern of adipokine levels In the food preference paradigm, -asarone produced selective decrease in HFD intake in rats. In obese rats, -asarone treatment not only reduced body weight but also prevented HFD-induced metabolic alterations, including glucose intolerance, dyslipidemia and adipokine imbal- ance. The observed beneficial effects of -asarone appear due its ability to reduce intake of energy dense food by affecting food palatability, and to normalize the levels of leptin and adiponectin in rats. Overall, our results suggest that -asarone is a novel candidate molecule with significant therapeutic potential in the management of obesity and associated abnormalities. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Obesity is a worldwide epidemic [1] and a heterogeneous com- plex disorder of multiple etiologies characterized by excessive deposition of body fat [2]. Obesity usually develops as a result of an imbalance between caloric intake and expenditure, which contribute to co-morbid conditions like hypertension, hyperlipi- demia, type II diabetes, coronary heart disease, stroke and cancer [3–5]. In developed countries, highly palatable foods are available in almost unlimited abundance, and overconsumption undoubt- edly contribute to the epidemic [6,7]. Sedentary lifestyles, high-fat, energy-dense diets, and a genetic predisposition all contribute to the obesity epidemic [8]. Abbreviations: HFD, high fat diet; FFA, free fatty acid; AC, Acorus calamus; IAEC, institutional animal ethics committee; INSA, indian national science academy; DTNB, 5,5 ′ dithiobis (2-nitrobenzoic acid); HDL, high density lipoprotein; p.o., per- oral; BMI, body mass index; OGTT, oral glucose tolerance test; ELISA, enzyme linked immunosorbent assay; PBS, phosphate buffer saline; TBARS, thiobarbituric acid reactive substances; BSA, bovine serum albumin; TC, total cholesterol; TG, triglycerides; MDA, malondialdehyde; GSH, reduced glutathione; ANOVA, analysis of variance. ∗ Corresponding author. E-mail address: malesh.thakre@gmail.com (M.M. Thakare). Herbs and phytochemicals have been known to play a major role in drug discovery process including anti-obesity molecules [9,10]. In recent years, the extract of Acorus calamus (AC) has been reported to improve metabolic functions [11,12]. A. cala- mus L., family Araceae, has been used in the Indian and Chinese systems of medicine for its valuable role in several CNS disor- ders [13–15]. In recent years, the extract of AC has been reported to hold hypoglycemic, hypolipidemic, insulin sensitizing and - glucosidase inhibitory activities [11,12,16], suggesting that it may play a role in regulation of metabolism. Moreover, ethyl acetate fraction of AC has also been reported to improve insulin release and attenuate postprandial hyperglycemia and cardiovascular compli- cations in mice [17]. -Asarone, a major constituent of AC has been reported to produce anti-adipogenic and lipolytic actions in 3T3- L1 cells, an action most likely exerted by subduing the expression of adipogenic transcription factors [18]. Thus, -asarone might be useful to correct energy imbalance and may prove to be beneficial in the management of obesity. Obesity can be characterized into two main types, hyperpla- sia (cell number increase) and hypertrophic (cell size increase) adipocytes. As a metabolic and endocrine organ, adipose tissue plays a critical role in regulation of energy balance, lipid metabolism and insulin action [19]. A chronic imbalance between energy intake and energy expenditure can lead to adipocyte http://dx.doi.org/10.1016/j.phrs.2015.12.003 1043-6618/© 2015 Elsevier Ltd. All rights reserved.