Endocrine Pharmacology Antihyperglycemic activity and antidiabetic effect of methyl caffeate isolated from Solanum torvum Swartz. fruit in streptozotocin induced diabetic rats Gopalsamy Rajiv Gandhi a , Savarimuthu Ignacimuthu a, ⁎, Michael Gabriel Paulraj a , Ponnusamy Sasikumar b a Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600 034, India b Department of Biochemistry, School of Biological Sciences, Centre for excellence in Functional Genomics, Madurai Kamaraj University, Madurai 625 021, India abstract article info Article history: Received 28 April 2011 Received in revised form 5 September 2011 Accepted 11 September 2011 Available online 24 September 2011 Keywords: Methyl caffeate Solanum torvum Diabetes mellitus Histological GLUT4 Natural remedies from medicinal plants are considered to be effective and safe alternatives to treat diabetes mellitus. Solanum torvum Swartz. fruit is widely used in the traditional system of medicine to treat diabetes. In the present study methyl caffeate, isolated from S. torvum fruit, was screened for its efficacy in controlling diabetes in animal models. Antihyperglycemic effect of methyl caffeate was studied in normal glucose-fed rats. The effects of oral administration of methyl caffeate (10, 20 and 40 mg/kg) for 28 days on body weight, fasting blood glucose, plasma insulin, hemoglobin, glycated hemoglobin, total protein, hepatic glycogen and carbohydrate metabolism enzymes in streptozotocin induced diabetic rats were investigated. Histological ob- servations in the pancreas and GLUT4 expression in skeletal muscles were also studied. Methyl caffeate at 40 mg/kg significantly prevented the increase in blood glucose level after glucose administration at 60 min in comparison to the hyperglycemic control group. In streptozotocin induced diabetic rats, methyl caffeate produced significant reduction in blood glucose and increased body weight. The levels and/or activities of other biochemical parameters were near normal due to treatment with methyl caffeate. Methyl caffeate trea- ted diabetic rats showed upregulation of GLUT4 and regeneration of β-cells in the pancreas. These results substantiated that methyl caffeate possessed hypoglycemic effect, and it could be developed into a potent oral antidiabetic drug. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia that involves abnormalities in both insulin secretion and action at peripheral tissues (Tian et al., 2003). The high concen- tration of blood glucose and other biochemical abnormalities results from a deficiency of insulin and/or from a subsensitivity to insulin in target cells (Annapurna et al., 2001). This includes impairment in the insulin signaling pathway leading to a failure of the insulin stimulated glucose uptake through GLUT4 (Glucose transporter 4) in targeted tissues like muscle and fat. In muscle cells, this is due to the inability of the insulin to stimulate the translocation of GLUT4 to the plasma membrane leading primarily to hyperglycemia (Sujatha et al., 2010). According to the World Health Organization (WHO), di- abetes mellitus is an ever-increasing disease (WHO, 2006). The dis- ease affects all components of the world but the percentages of diabetics in global population are particularly high in Asia and Europe (World Diabetes Foundation (WDF), 2010). The practice of herbal medicine to treat diabetes mellitus is almost universal among non- industrialized societies (Singh et al., 2001). The WHO estimated that 80% of the diabetic people in the world's population presently depend upon herbal medicine for their successive treatments (WHO, 2008). Antidiabetic agents from medicinal plants could serve as a good source for drug design and much attention has been fixed on formu- lations of herbal medicine (Vishwakarma et al., 2010). Solanum torvum Swartz. (Solanaceae) is a diminutively minuscule shrub distributed widely in South India, Malaya, China, Philippines and Tropical America. Its edible fruits, commonly available in the markets, are utilized as vegetable and are regarded as essential ingre- dients in the South Indian population's diet. Pharmacological studies on this fruit demonstrated antidiabetic (Gandhi et al., 2011), anti- microbial, antioxidant, antiviral, immuno-secretory, analgesic, anti- inflammatory, cardiovascular and anti-platelet aggregation activities (Mohan et al., 2009). Chemical constituents reported from the S. torvum fruit include isoflavonoid sulfate, steroidal glycosides, chlorogenone, neochlorogenone, triacontane derivatives, 22-β-O- spirostanol oligoglycosides, 26-O-β-glucosidase, rutin, caffeic acid, gallic acid, catechin, pyrogallol (Kusirisin et al., 2009; Mohan et al., 2009) and methyl caffeate (Takahashi et al., 2010). Methyl caffeate isolated from the S. torvum fruit possessed α- glucosidase inhibition activity in rat intestine (Takahashi et al., 2010). The protective efficacy of methyl caffeate has been reported in cellular models of oxidative stress (Ishige et al., 2001). European Journal of Pharmacology 670 (2011) 623–631 ⁎ Corresponding author at: Entomology Research Institute, Loyola College, Nungambakkam, Chennai 600 034, India. Tel.: +91 044 28178348; fax: +91 044 28175566. E-mail address: entolc@hotmail.com (S. Ignacimuthu). 0014-2999/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2011.09.159 Contents lists available at SciVerse ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar