Evaluation of biochemical mechanisms of anti-diabetic functions of Anisomeles malabarica.

Anisomeles malabarica (AM) is an aromatic plant traditionally used for the treatment of diabetes mellitus in India. Following bioassay guided fractionation, we recently identified an active fraction of AM (AMAF, with potential mix of active principles) that showed significant antihyperglycemic and antihyperlipidemic activities. In addition, AMAF treatment improved insulin levels. However, the biochemical mechanism/s through which AMAF demonstrates the antidiabetic effects is largely unknown. Based on its beneficial effects we investigated the biochemical mechanism of the anti-diabetic activity of A.malabarica active fraction (AMAF) in streptozotocin (STZ) induced diabetic rats. Streptozotocin induced diabetic rats were treated with AMAF (50 mg AMAF/kg/day) for 30 days and alterations in the body weights, glycogen and protein content of tissues, functional markers of hepatic and renal tissues, carbohydrate metabolic enzymes and their genes expression were evaluated. Lipid peroxides levels and activities of antioxidant enzymes of hepatic and renal tissues were also measured. The AMAF treatment resulted in increase in body weights, hepatic and renal protein and tissue glycogen levels in diabetic treated rats compared to diabetic rats. In addition, the treatment improved activities of carbohydrate metabolic enzymes, antioxidant enzymes and, liver and renal functional markers in the AMAF treated diabetic rats. Gene expressions of key carbohydrate metabolic enzymes/factors glucokinase, glucose transporter protein (GLUT-2) and phosphoenolpyruvate carboxykinase (PEPCK) were also normalized up on AMAF treatment in diabetic rats. Our studies indicate that the isolated active fraction of AM (AMAF) from the leaves of A.malabarica positively regulated the glucose homeostasis and oxidative stress through carbohydrate metabolism and antioxidant enzyme activities respectively in hepatic and renal tissues.

Anti-Diabetic Potential of the Leaves of Anisomeles malabarica in Streptozotocin Induced Diabetic Rats.

BACKGROUND/AIMS: Diabetes mellitus is a pandemic metabolic disorder that is affecting a majority of populations in recent years. There is a requirement for new drugs that are safer and cheaper due to the side effects associated with the available medications. METHODS: We investigated the anti-diabetic activity of leaves of Anisomeles malabarica following bioactivity guided fractionation. The different solvent (hexane, ethyl acetate, methanol and water) extracts of A. malabarica leaves were used in acute treatment studies to evaluate and identify the active fraction. The ethyl acetate extract was subjected to further fractionation using silica gel column chromatography and the compounds were identified by LC-SRM/MS and GC-MS. Additional chronic treatment studies were carried out using this active fraction (AMAF) for 30 days in experimental diabetic rats. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), plasma insulin levels and glucose tolerance were measured along with insulin resistance/sensitivity indicators (HOMA-IR, HOMA-ß and QUICKI) to assess the beneficial effects of A. malabarica in the management of diabetes mellitus. RESULTS: Among the different solvent extracts tested, ethyl acetate extract showed maximum (66%) anti-hyperglycemic activity. The hexane and ethyl acetate (1: 1) fraction that has maximum anti-diabetic activity was identified as active fraction of A. malabarica (AMAF). The FBG, HbA1c, plasma insulin levels and insulin sensitivity/resistance indicators such as glucose tolerance, HOMA-IR, HOMA-ß and QUICKI were significantly improved to near normal in diabetic rats treated with AMAF. Further, we identified key flavonoids and fatty acids as the anti-diabetic active principles from the AMAF of A. malabarica leaves. CONCLUSION: The results of our study suggest that Anisomeles malabarica has potential anti-diabetic activity in STZ induced diabetic rats.