Endocrine Pharmacology Effect of iridoid glucoside on streptozotocin induced diabetic rats and its role in regulating carbohydrate metabolic enzymes Ramalingam Sundaram a , Rajendran Naresh a , Rajakumaravelu Ranadevan a , Palanivelu Shanthi b , Panchanatham Sachdanandam a, ⁎ a Department of Medical Biochemistry, Dr. ALM P-G, Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu-600113, India b Department of Pathology, Dr. ALM P-G, Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu-600113, India abstract article info Article history: Received 29 November 2010 Received in revised form 18 October 2011 Accepted 30 October 2011 Available online 9 November 2011 Keywords: Vitex negundo Iridoid glucoside Diabetes Streptozocin Hepatic key enzyme Vitex negundo is a medicinal plant used to treat many ailments. An active compound of iridoid glucoside was isolated from V. negundo leaves and its efficacy was investigated in streptozotocin induced diabetic rats with special reference to carbohydrate metabolizing enzymes. The optimum dose of iridoid glucoside was deter- mined by oral glucose tolerance test. The effects of iridoid glucoside were compared with glibenclamide Ad- ministration of iridoid glucoside (50 mg/kg body weight) to diabetic rats for 30 days resulted in significant reduction in the levels of plasma glucose, glycosylated hemoglobin and increase in the levels of insulin and hemoglobin. Administration of iridoid glucoside showed a significant increase in the levels of glycolytic en- zymes and glycogen content and decrease in the levels of gluconeogenic enzymes in the liver of diabetic trea- ted rats. Further, iridoid glucoside showed antihyperlipidemic activity as evidenced by significant reduction in serum total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein coupled to- gether with elevation of high density lipoprotein in diabetic rats. A significant decrease was observed in the activities of aspartate aminotransferase, alanine aminotransferase and decrease in the levels of serum urea and creatinine in diabetic treated rats when compared to diabetic untreated rats. Treatment of iridoid gluco- side alleviated body weight loss in diabetic rats. The effect produced by iridoid glucoside on various param- eters was comparable to that of glibenclamide. These results indicate that iridoid glucoside possess antihyperlipidemic effect in addition to its antidiabetic effect. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Diabetes mellitus is a syndrome, initially characterized by the loss of glucose homeostasis resulting from defects in insulin secretion, insulin action or both (Scheen, 1997). Recent studies indicate that at present there are 150 million people in the world with diabetes and this is likely to increase to 300 million or more by the year 2025 (King et al., 1998). Reasons for this rise which includes sedentary lifestyle, consumption of energy rich diet, obesity, higher life span and others (Yajnik, 2001). The epidemiological and clinical studies strongly support the impression that hyperglycemia is the main cause of long-term complications of di- abetes; it induces auto-oxidation of glucose, glycation of proteins and activation of polyol metabolism (Lee and Chung, 1999). These changes play a vital role in the pathogenesis of diabetes and accelerate the devel- opment of diabetic complications (Lu et al., 2008). Some of the charac- teristic long-term complications of diabetes are coronary artery disease, cerebrovascular disease, renal failure, blindness, limb amputation, neu- rological complications and pre-mature death (Subash Babu et al., 2007). The single high dose streptozotocin-induced diabetic rat is one of the animal models which mimic the human insulin dependent diabe- tes mellitus (IDDM) or type I diabetes. In this type I model of diabetes, insulin is markedly depleted, but not absent (Pushparaj et al., 2001). Liver is an insulin dependent tissue which is severely affected during di- abetes mellitus and decreased activities of enzymes in the glycolytic and pentose phosphate pathways, while increasing the activities of gluco- neogenic and glycogenolytic pathways (McAnuff et al., 2005). Currently, there are different groups of oral hypoglycemic agents for clinical use and having characteristic profiles of side effects (Kameswara Rao et al., 1997; Williams and Pickup, 1991). Management of diabetes without any side effects is still a challenge to the medical system. This leads to increasing demand for natural products with antidiabetic activ- ity and less side effects. Indian traditional medicines belong to one of the richest medicinal systems among those available in the world. Many Indian medicinal plants have been found to be successfully used to manage diabetes and some of them have been tested and the active principles were isolated. Therefore, the search for more effective and safer hypoglycemic agents has continued to be an important area of ac- tive research. Further, after the recommendations made by WHO on di- abetes mellitus (WHO, 1980), investigation on hypoglycemic agents from medicinal plants have become more important. European Journal of Pharmacology 674 (2012) 460–467 ⁎ Corresponding author. Tel.: + 914424547082. E-mail address: psachdanandam2000@yahoo.co.in (P. Sachdanandam). 0014-2999/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2011.10.039 Contents lists available at SciVerse ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar