In vitro Enhancement of Pancreatic β Cells MIN6 Proliferation by Insulinotropic Gymnema sylvestre Aqueous Extracts: Evidence-based Regenerative Therapeutic Capacity of a Medicinal Herb
Violet Kasabri *
Faculty of Pharmacy, University of Jordan, Queen Rania Street, Amman 11942, Jordan.
Fatma U. Afifi
Faculty of Pharmacy, University of Jordan, Queen Rania Street, Amman 11942, Jordan.
Yasser Bustanji
Faculty of Pharmacy, University of Jordan, Queen Rania Street, Amman 11942, Jordan.
Sundus Mashallah
Faculty of Pharmacy, University of Jordan, Queen Rania Street, Amman 11942, Jordan.
Randa Naffa
Faculty of Medicine, University of Jordan, Queen Rania Street, Amman 11942, Jordan.
Hala S. Mehdi
Jordan University Hospital, Queen Rania Street, Amman 11942, Jordan.
*Author to whom correspondence should be addressed.
Abstract
Aim: To show that Gymnema sylvestre (Roxb.) Asclepiadaceae not only has antidiabetic propensities, but it most likely works by regeneration of pancreatic β cells which is imperative in anti-obesity-diabetes therapeutic applications of medicinal plants.
Study Design: The present study design investigated the effects of G. sylvestre leaves crude aqueous extracts (AEs), traditionally utilized in diabetes treatment, on the pancreatic β-cell MIN6 proliferation and insulin secretion and extrapancreatic dietary carbohydrate and lipid digestion
Place and Duration of Study: Faculty of Pharmacy, The University of Jordan, 2008-2012.
Results: Comparable to GLP-1 (500 nM) pancreatic proliferative capacity; G. sylvestre AE concentrations (0.01 and 0.1 mg/mL) induced MIN6 monolayers expansion by respective 130.3% and 127.4% (P<0.001 vs. spontaneous control). Like L-alanine (10 mM) insulinotropic efficacy and without exerting cytotoxicity, glucose-stimulated insulin secretion was potentiated by G. sylvestre AEs (5, 10 and 25 mg/mL) (711.0%, 843.0% and 906.5%, respectively, P<0.001 vs. basal control). The potent plants’ insulin secretory bioactivities were abolished in the depleted Ca2+ conditions (P<0.001). Similar to orlistat antilipolytic efficacy, pancreatic lipase IC50 value for G. sylvestre AEs was 106.3±7.2 μg/mL. Unlike acarbose (100 μg/mL) dual inhibition of α-amylase/α-glucosidase, G. sylvestre AE was inactive at used doses. Dissimilar to guar gum (50 mg/mL) diffusional hindrance in a simple dialysis model, G. sylvestre AEs (10, 25 and 50 mg/mL) proved inactive. This in vitro ineffectiveness was mirrored in respective in vivo oral carbohydrate tolerance tests in overnight fasting normoglycemic rats.
Conclusion: This evaluation has revealed that G. sylvestre leaves AEs augmented β-cell expansion and potentiated glucose-evoked Ca2+-regulated insulin secretion; combined with impressive antilipolytic activity. These actions depend on the bioactive water soluble phyto-principles intact absorption in vivo. Future directives may assess the potential of G. sylvestre as a new alternative for anti-obesity-diabetes pharmacotherapy and prevention.
Keywords: Gymnema sylvestre, β-cell regeneration and proliferation, pancreatic insulin secretion, α-amylase/α-glucosidase, pancreatic triacylglycerol lipase