Endocrine Pharmacology Antidiabetic activity of γ-sitosterol isolated from Lippia nodiflora L. in streptozotocin induced diabetic rats Rangachari Balamurugan, Veeramuthu Duraipandiyan, Savarimuthu Ignacimuthu ⁎ Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India abstract article info Article history: Received 9 November 2010 Received in revised form 26 April 2011 Accepted 11 May 2011 Available online 7 June 2011 Keywords: Lippia nodiflora Streptozotocin γ-Sitosterol Antidiabetic Insulin Hepatic marker enzyme Lippia nodiflora L. (Verbenaceae) is a creeping perennial herb widely used in traditional system of medicine to treat ulcers, bronchitis and heart diseases; it also possesses antidiabetic property. In the present study, γ-sitosterol isolated from Lippia nodiflora was screened for its antidiabetic property in streptozotocin (STZ) induced diabetic rats. Insulin secretion in response to glucose was evaluated in isolated rat islets. Oral administration of γ-sitosterol (20 mg/kg body weight) once daily for 21 days in STZ-induced diabetic rats resulted in a significant decrease in blood glucose and glycosylated hemoglobin with a significant increase in plasma insulin level, body weight and food intake. Furthermore γ-sitosterol showed antihyperlipidemic activity as evidenced by significant decrease in serum total cholesterol, triglycerides and very low density lipoprotein-cholesterol levels coupled with elevation of high density lipoprotein-cholesterol levels in treated rats. A significant decrease in the activities of alanine aminotransaminase, aspartate aminotransaminase, alkaline phosphatase and acid phosphatase in γ-sitosterol treated rats when compared to diabetic control rats indicated its protective role against liver damage. γ-Sitosterol increased insulin secretion in response to glucose. Immunohistochemical study of pancreas also confirmed the biochemical findings. These results indicated that γ-sitosterol, the compound isolated from L. nodiflora, possessed antihyperglycemic activity. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Type 2 diabetes mellitus, also known as noninsulin dependent diabetes mellitus, develops in middle or later life and affects 2–6% of adults in most Western societies (Bailey, 2000). World Health Organization (WHO) estimates that more than 220 million people worldwide have diabetes and this number is likely to double by 2030 (Aragao et al., 2010). The pharmacological agents currently used for the treatment of type 2 diabetes include sulfonylurea, biguanide, thiazolidinedione and α-glycosidase inhibitors. These agents, how- ever, have restricted usage due to several undesirable side effects and fail to significantly alter the course of diabetic complications (Rang and Dale, 1991). The high prevalence of diabetes as well as its long- term complications has led to an ongoing search for hypoglycemic agents from natural sources (Nicasio et al., 2005). Herbal remedies have been used since ancient times for the treatment of diabetes mellitus. About 90% of the world population in rural areas of developing countries relies solely on traditional medicines for their primary health care (Hassan et al. 2010). Lippia nodiflora L. (Verbenaceae) is a creeping perennial herb with small white flowers; it is found in wet grounds and grassy pastures. The plant is distributed throughout India, Ceylon, Baluchistan, and Africa. In the Ayurveda system the plant is used as an aphrodisiac and to treat ulcers, bronchitis and heart diseases. In Yunani medicine, the plant is used as diuretic and to treat fever and cold. The herb possesses cooling and diuretic properties and stops knee joint pain. The plant made into a poultice is used as a maturant for boils (Durairaj et al. 2008). Antimalarial activity has been reported from the herb (Mukherjee, 1991); leaves of the plant were reported to possess anti-inflammatory, analgesic, and antipyretic activity (Forestieri et al., 1996). Gastro- protective effect has also been described (Khalil et al., 2007). Hypoglycemic property of a methanol extract of L. nodiflora has been reported by us (Balamurugan et al., 2010). Resin, stigmasterol, β-sitosterol, sugars (Pacual et al., 2001) as well as essential oil constituents such as monoterpenes and sesquiterpenes (Terblanche and Kornelius, 1996) have been isolated from the plant and identified. Presence of Lippiflorin A and Lippiflorin B, flavonoids like nepetin, jaceosidin, hispidulin, flavone monosulfates and flavone disulfates has also been reported from aerial parts (Tomas-Barberan et al., 1987). γ-Sitosterol, a steroidal compound, was isolated from L. nodiflora by us. It has been previously isolated from soya and its antihyperlipidemic activity has been described (Best et al., 1954). The same compound has also been reported to occur in Abelmoschus manihot (Jain et al., 2009) and Polygonum bistorta (Manoharan et al., 2005). There European Journal of Pharmacology 667 (2011) 410–418 ⁎ Corresponding author at: Entomology Research Institute, Loyola College, Nungambakkam, Chennai 600 034, Tamil Nadu, India. Tel.: +91 44 2817 8348; fax: + 91 44 2817 5566. 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.2011.05.025 Contents lists available at ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar