MANGIFERIN: A POTENTIAL NATURAL MOLECULE FOR MANAGEMENT OF METABOLIC SYNDROME Review Article PAVAN KUMAR MUJAWDIYA, SUMAN KAPUR Birla Institute of Technology and Science-Pilani, Hyderabad campus, Jawahar Nagar, Shameerpet mandal, Hyderabad-500078 Email: skapur@hyderabad.bits-pilani.ac.in Received: 15 May 2015 Revised and Accepted: 07 Aug 2015 ABSTRACT The incidence of metabolic syndrome is rising at an unprecedented pace. The technological advancements, lifestyle changes and mechanization are all considered responsible for this rising global health issue. Nature-derived phytochemicals possess several unique properties that may be usefulformanagement of metabolic syndrome. Mangiferin, present in various plant species, has been shown to have anti-obesity, anti-diabetic, anti- oxidant and anti-inflammatory properties. Mangiferin also modulates glucose and lipid metabolisms and restores glucose and lipid homeostasis. In this review, we attempt to provide the latest information available on mangiferin and its effects on various biological processes associated/implicated in metabolic syndrome. Keywords: Mangiferin, Metabolic syndrome, Obesity, Type 2 diabetes, Inflammation, Oxidative stress. INTRODUCTION Metabolic syndrome is a constellation of closely associated disorders whose common root cause is the sedentary lifestyle, intake of calorie-rich diet, reduced physical activity sleep deprivation and stress. This group of symptoms comprises of obesity, type 2 diabetes mellitus, insulin resistance and hyperglycemia, hypertension, non- alcoholic fatty liver disorder, cardiovascular disorders and dyslipidemia [1]. One of the principal causes behind metabolic syndrome is obesity. The obesity epidemic represents a serious public health concern due to its increasing incidence and associated risk profile for several diseases and consequent morbidity and mortality. A recent report by the WHO states that globally 39% of adults aged 18 and over, were overweight in 2014, and 13% were falling under the obese category [2]. Natural compounds and herbs have been traditionally used to treat and cure various disorders associated with imbalanced metabolism. Based on the fact that plants have been used to manage human health for more than 3000 y, and that they are easily available to local populations, use of plant derived herbal products for the management of obesity, and diabetes is an attractive and promising area of research. Ancient Ayurvedic texts describe several herbs and herbal extracts for treatment of obesity and associated metabolic syndrome. Various studies have described the benefits of using plant extracts for treatment of obesity, insulin resistance, type 2 diabetes, and polycystic ovary syndrome in obese individuals [3-6]. In the present review, we summarize the therapeutic potential of one such molecule, mangiferin, for treatment of metabolic syndrome as it modulates several biological processes related to energy generation, energy expenditure and metabolism. Chemical properties and occurrence of mangiferin Mangiferin is a naturally-occurring polyphenol of C- glycosylxanthone structure with diverse pharmacological actions. Mangiferin is widely present in higher plants. It is present in higher concentration in Mangifera indica, Cyclopia and Salacia species. Mangiferin has been reported to possess analgesic, anti-diabetic, anti-sclerotic, antimicrobial, antiviral, cardio-, hepato-, and neuro- protective, anti-inflammatory and anti-allergic properties. It is sold for treatment of metabolic disorder in Cuba under the trade name of Vimang [7, 8]. The presence of catechol moiety containing four hydroxyl groups makes mangiferin an efficient anti-oxidant and anti-free radical molecule [8, 9]. Mangiferin is poorly soluble in aqueous solutions. Solubility and intestinal permeability of mangiferin is found to be increased through its complexation with phospholipids enhancing the bioavailability by 2.3 times compared with crude mangiferin in experimental rats [10]. Complexation of mangiferin with β-cyclodextrin also improves thermal stability and water solubility of mangiferin revealing the potential usefulness of mangiferin derivatives in preparation of novel thermally stable formulations [11]. Fig. 1: Structure of mangiferin Mangiferin ameliorates obesity and associated metabolic syndrome Onset of metabolic syndrome disrupts the homeostatic balance between various organs such as the liver, pancreas, heart, brain, adipose tissue and various other regulatory cells throughout the body [1]. Herbal extracts of Mangifera indica whose principle component is mangiferin have been shown to counteract obesity/metabolic syndrome. It has been demonstrated that 1% mango seed kernel extract in hot water (MESK-W) prevented weight gain and liver steatohepatitis in ahigh fat diet treated mice [12]. Kobayashi et al. have shown that in 3T3-L1 adipocytes, 1% MESK-W inhibited cellular lipid deposition by reducing glycerol 2-phosphate dehydrogenase activity and PPARγ and C/EBPα expression levels [12]. Moreno et al. have shown that ethanolic extract of Mangifera indica from both stem bark and leaves inhibitthe action of pancreatic lipase, and lipoprotein lipase, reduce fat absorption and increase fecal fat excretion. Moreover, Mangifera indica extract down- regulated the expression of several genes associated with the pathophysiology of obesity and inflammation such as lipoprotein lipase, hormone-sensitive lipase, fatty acid synthase and resistin in liver and epididymal fat [13]. Moreover, it was found to decrease the expression DGAT2, SREBP-1c, ACC genes, and up-regulated CD36, PPAR-α, CPT-1 expression and prevented fat deposition in visceral fat pad and liver [14, 15]. Similar studies in our lab have proven that ethanolic extract of Mangifera indica seed kernel prevented weight gain in diet-induced obese mice, which was comparable with standard anti-obesity drug Orlistat [16]. The inflammatory response International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Supple 1, 2015 Innovare Academic Sciences