In vitro Modulation of Pancreatic Insulin Secretion and Extra Pancreatic Insulin Action, Enzymatic Starch Digestion and Protein Glycation by Terminalia chebula Extracts.

Aim: Traditional plant treatments have been used throughout the world for the therapy of diabetes mellitus. Study Design: Using multiple in vitro models; this study was designed to investigate the efficacy and mode of action of Terminalia chebula Retz. (Combretaceae) used traditionally for treatment of diabetes. Place and Duration of Study: School of Biomedical Sciences, University of Ulster, 2001- 2004. Results: T. chebula aqueous extract stimulated basal insulin output and potentiated glucose-stimulated insulin secretion concentration-dependently in the clonal pancreatic beta cell line, BRIN-BD11 (p<0.001). The insulin secretory activity of plant extract was abolished in the absence of extracellular Ca2+ and by inhibitors of cellular Ca2+ uptake, diazoxide and verapamil, (p<0.001). Furthermore, the extract increased insulin secretion in depolarised cells and augmented insulin secretion triggered by IBMX, but not by tolbutamide or glibenclamide. T. chebula extract did not display insulin mimetic activity but it enhanced insulin-stimulated glucose transport in 3T3 L1 adipocytes by 280% (p<0.001). At (0.5-5.0mg/mL) concentrations, the extract also produced 22-84% (p<0.001) decrease in starch digestion In vitro and inhibited protein glycation (p<0.001) at 1mg/ml aqueous extract. Conclusion: This study has revealed that water soluble bioactive principles in T.chebula extract stimulate insulin secretion, enhance insulin action and inhibit both protein glycation and starch digestion. The former actions are dependent on the bioeffective component(s) in the plant being absorbed intact. Future work assessing the use of Terminalia chebula as dietary adjunct or as a source of active antidiabetic agents may provide new opportunities for the treatment of diabetes

Emblica officinalis Stimulates the Secretion and Action of Insulin and Inhibits Starch Digestion and Protein Glycation In vitro.

Aim: Medicinal, edible and aromatic plants and natural products have been used worldwide for the management of diabetes mellitus. The aim of this study was to investigate the efficacy and mode of action of Emblica officinalis Gaertn. (Phyllanthaceae) used traditionally for treatment of diabetes. Study Design: Using multiple In vitro models; this study was designed to investigate the antidiabetes efficacy and mode of action of E. officinalis. Place and Duration of Study: School of Biomedical Sciences, University of Ulster, 2001- 2004 Results: E. officinalis aqueous extracts (AEs) stimulated basal insulin output and potentiated glucose-stimulated insulin secretion concentration-dependently in the clonal pancreatic beta cell line, BRIN-BD11 (p<0.001). The insulin secretory activity of plant extract was abolished in the absence of extracellular Ca2+ and by inhibitors of cellular Ca2+ uptake, diazoxide (p<0.001, n=8). Furthermore, the extract increased insulin secretion in depolarised cells and further augmented insulin secretion triggered by IBMX and tolbutamide. E. officinalis AE (1 mg/mL) displayed insulin mimetic activity (230%, p<0.001). Furthermore, it enhanced insulin-stimulated glucose transport in 3T3 L1 adipocytes by 460% (p<0.001). E. officinalis augmented also synergistically (p<0.001) insulin action, when co-incubated with insulin sensitizers; metformin (2.4-fold), vanadate (4.9-fold), tungstate (4.8-fold) and molybdate (6-fold). At higher concentrations (0.5-5 mg/mL), the extract also produced 8-74% (p<0.001) decrease in enzymatic starch digestion In vitro. E. officinalis AEs (1-50 mg/mL) inhibited protein glycation 44-87% (p<0.001). Conclusion: This study has revealed that water soluble bioactive principles in E. officinalis extract stimulate insulin secretion, enhance insulin action and inhibit both protein glycation and starch digestion. The former actions are dependent on the bioeffective component (s) in the plant being absorbed intact. Future work assessing the use of Emblica officinalis as adjunctive therapeutic nutraceutical or as a source of bioactive antidiabetic principles may provide new opportunities for the integrated management/prevention/reversal of diabetes.