Journal of Experimental and Integrative Medicine DOI: 10.5455/jeim.160814.or.110 www.scopemed.org 268 J Exp Integr Med ● Oct-Dec 2014 ● Vol 4 ● Issue 4 INTRODUCTION Diabetes mellitus is a major health problem, which is emerging as a pandemic contemporaneous with changes in lifestyle and longer life-expectancy [1]. Treatment of diabetes is advancing on a number of fronts, ranging from better understanding of the mechanisms of action of existing agents to the development of new drugs [2]. Regimens currently employed include lifestyle modification, oral-antidiabetic drugs and more widespread use of insulin therapy. Despite their usefulness, none of these treatments either alone or/in combination can mimic physiological insulin release or prevent the development of chronic complications [3]. Nature is an exemplary source of medications, and indigenous remedies have been used in the treatment of diabetes mellitus in many parts of the world since the 6 th century BC [4]. Use of traditional medicines in the treatment of diabetes mellitus is probably based primarily on the alleviation of its obvious symptoms such as pronounced thirst and polyuria. Recently, there has been a renaissance of clinical, pharmaceutical and scientific interest in the potential of plant treatments. However out of an estimated 250,000 higher plants, it is estimated that < 1% has been screened pharmacologically [5,6]. Swertia chirayita is a medicinal plant indigenous to temperate Himalaya and its medicinal usage has been reviewed previously. It is widely esteemed in Ayurvedic medicine and also used as a bitter tonic in the treatment of fever and various skin diseases [7]. Increasing body of evidence also support the use of this herb in the treatment of diabetes [8]. Swerchirin (1,8-dihydroxy- 3,5-dimethoxy xanthone), derived from the hexane fraction of S. chirayita, has demonstrated anti-hyperglycemic activity in fasted, fed, glucose-loaded, tolbutamide pre-treated and streptozotocin-induced diabetic rats [9-11]. However, mechanisms by which S. chirayita ameliorates hyperglycemia are not fully understood. The present study investigated the effects of aqueous extracts of S. chirayita bark on insulin secretion and glucose uptake at the cellular level and assessed its effects on protein glycation in vitro. Antidiabetic actions of aqueous bark extract of Swertia chirayita on insulin secretion, cellular glucose uptake and protein glycation Heather-Anne J. Thomson, Opeolu O. Ojo, Peter R. Flatt, Yasser H. A. Abdel-Wahab Original Research SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK Address for correspondence: Address for correspondence: Opeolu Oyejide Ojo, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom. E-mail: o. ojo@ulster.ac.uk Received: Received: August 04, 2014 Accepted: Accepted: August 16, 2014 Published: Published: December 07, 2014 ABSTRACT Objective: There is renewed scientific interest in the potential of plant-derived agents for the treatment of diabetes mellitus. This study investigated the antidiabetic actions of Swertia chirayita, a plant used traditionally in the management of diabetes. Materials and Methods: Insulin secretion from BRIN-DB11 cells was assessed in the absence or presence of plant extract and modulators of beta cell function. Glucose uptake was assessed using 3T3-L1 cells while effects of the plant extract on protein glycation was assessed using model peptide. Insulin was measured by radioimmunoassay and intracellular calcium by FlexStation ® . Results: S. chirayita significantly stimulated concentration-dependent insulin secretion from BRIN-BD11 cells. Its insulinotropic effects were abolished in the absence of extracellular Ca 2 + or by diazoxide and were significantly decreased by verapamil and in beta cell depolarization with KCl. S. chirayita extracts evoked a 28-59% increase in basal and insulin-stimulated glucose uptake by 3T3-L1 cells. Protein glycation was significantly inhibited by S. chirayita in a dose-dependent manner. Conclusion: This study reveals that the antidiabetic actions of S. chirayita aqueous bark extracts involves the stimulation of insulin secretion and enhancement of insulin action. Inhibition of protein glycation may also help counter diabetic complications. These actions of S. chirayita may provide new opportunities for the treatment of diabetes. KEY WORDS: Insulin action, protein glycation, Swertia chirayita, Type 2 diabetes