Copyright © 2009 John Wiley & Sons, Ltd. Phytother. Res. 23, 1140–1145 (2009) DOI: 10.1002/ptr 1140 R. JATWA AND A. KAR Copyright © 2009 John Wiley & Sons, Ltd. PHYTOTHERAPY RESEARCH Phytother. Res. 23, 1140–1145 (2009) Published online 23 January 2009 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/ptr.2765 Amelioration of Metformin-induced Hypothyroidism by Withania somnifera and Bauhinia purpurea Extracts in Type 2 Diabetic Mice Rameshwar Jatwa* and Anand Kar Endocrine Research Unit, School of Life Sciences, Devi Ahilya University, Indore, M.P., India-452001 An investigation was carried out to reveal the possible ameliorative role of two plant extracts on an antidiabetic drug-induced hypothyroidism in Type 2 diabetic animals. Dexamethasone (1.0 mg/kg, i.m.) administration caused hyperglycemia with a parallel increase in renal lipid peroxidation (LPO), relative risk ratio (RR), and the concentrations of serum insulin; total cholesterol (TC); low-density lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TG). It decreased serum triiodothyro- nine (T 3 ), thyroxine (T 4 ) and high-density lipoprotein cholesterol (HDL-C) levels as well as renal superoxide dismutase (SOD); catalase (CAT) and reduced glutathione (GSH) content. Administration with metformin (150 mg/kg, orally) to diabetic animals further reduced circulating T 4 level and caused severe hypothyroidism. It also reduced renal LPO, RR, serum concentrations of insulin; glucose and LDL-C with a parallel increase in cellular antioxidants. While oral administration with either Withania somnifera (1.4 g/kg) or Bauhinia purpurea (2.5 mg/kg) extract along with dexamethasone and metformin elevated the concentra- tions of circulating T 3 and T 4 to euthyroid level. The plant extracts also corrected RR ratio and serum concentration of lipids. The findings of the present study, for the first time, reveal that the evaluated plant extracts have a potential to ameliorate metformin-induced hypothyroidism in Type 2 diabetic subjects. Copyright © 2009 John Wiley & Sons, Ltd. Keywords: dexamethasone; lipid peroxidation; metformin; mice; thyroid hormones; Type 2 diabetes mellitus. INTRODUCTION Diabetes mellitus is a syndrome characterized by distur- bed carbohydrate, fat and protein metabolism leading to inappropriate hyperglycemia, either due to low levels of the hormone insulin, or to the abnormal resistance to its fucntions (Ganong, 2005; Ma et al., 2007; Mlinar et al., 2007). The World Health Organization recognizes three main forms of diabetes mellitus i.e. Type 1, Type 2, and gestational diabetes. Out of these, Type 2 diabetes mellitus comprises about 90–95% of the diabetic popu- lation, in which target cells fail to respond to normal level of circulating insulin (Roith et al., 2000; Bucking- ham, 2006; Mlinar et al., 2007). The etiology of Type 2 diabetes in which beta cells of the pancreas are very often functional includes genetic and other factors such as food intake; reduced physical activity; aging, smoking, administration of drugs and hormonal imbalance (Buckingham, 2006; Mlinar et al., 2007). Among the hormones, adrenocorticoids are well known for their diabetogenic effects and are respons- ible for most of the steroid diabetes (Roith et al., 2000; Jatwa and Kar, 2006a; Jatwa et al., 2007). For the treat- ment of Type 2 diabetes mellitus, several oral hypoglycemic agents including thiazolidinediones, sulphonylureas, alpha-glucosidase inhibitors, and biguanides are commonly in use. Metformin is a member of biguanides group of oral hypoglycemic drugs, and has been used for the treatment of Type 2 diabetes mellitus for many years across the globe (Vigerrsky et al., 2006). However, some recent clinical reports have indicated that metformin therapy may result in negative alteration in thyroid metabolism and lead to drug-induced hypothyroidism (Vigerrsky et al., 2006; Isidro et al., 2007). Herbal drugs are gradually becoming more popular and acceptable, as they are believed to be safe (Kar and Panda, 2005; Hamza et al., 2008). In recent years, ample work has been done on phytomedicine. In general, there is a paucity of scientific literature on the regulation of allopathic drug-induced hormonal imbalance and oxidative stress by herbal extracts. To the best of our knowledge, to date there is no report available on the ameliorating role of plant extracts on antihyperglycemic drug-induced thyroid dysfunction, despite the fact that several plant extracts have been investigated for the regulation of altered thyroid metabolism and diabetes mellitus (Panda and Kar, 1999; Kar and Panda, 2005; Babu et al., 2007). In the present study, an attempt has been made to work out the possible amelioration of metformin-induced hypothyroidism in dexamethasone-induced Type 2 dia- betic mice (Jatwa and Kar, 2006a; Jatwa et al., 2007) by simultaneous therapy of Withania somnifera root or Bauhinia purpurea bark extracts which are known as pro-thyroid agents (Panda and Kar, 1999). As it is well documented that in diabetes mellitus renal tissues are * Correspondence to: Rameshwar Jatwa, Endocrine Research Unit, School of Life Sciences, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore 452001, MP, India. E-mail: rjatwa80@hotmail.com Received 13 August 2008 Revised 18 October 2008 Accepted 24 November 2008