Alpha-Mangostin Improves Insulin Secretion and Protects INS-1 Cells from Streptozotocin-Induced Damage

Abstract

Alpha ()-mangostin, a yellow crystalline powder with a xanthone core structure, is isolated from mangosteen (Garcinia mangostana), which is a tropical fruit of great nutritional value. The aim of the present study was to investigate the anti-diabetic effects of -mangostin and to elucidate the molecular mechanisms underlying its effect on pancreatic beta ()-cell dysfunction. To assess the effects of -mangostin on insulin production, rat pancreatic INS-1 cells were treated with non-toxic doses of -mangostin (1-10 M) and its impact on insulin signaling was examined by Western blotting. In addition, the protective effect of -mangostin against pancreatic -cell apoptosis was verified by using the -cell toxin streptozotocin (STZ). Our results showed that -mangostin stimulated insulin secretion in INS-1 cells by activating insulin receptor (IR) and pancreatic and duodenal homeobox 1 (Pdx1) followed by phosphorylation of phospho-phosphatidylinositol-3 kinase (PI3K), Akt, and extracellular signal regulated kinase (ERK) signaling cascades, whereas it inhibited the phosphorylation of insulin receptor substrate (IRS-1) (Ser1101). Moreover, -mangostin was found to restore the STZ-induced decrease in INS-1 cell viability in a dose-dependent manner. In addition, treatment of INS-1 cells with 50 M STZ resulted in an increase in intracellular reactive oxygen species (ROS) levels, which was represented by the fluorescence intensity of 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA). This oxidative stress was decreased by co-treatment with 5 M -mangostin. Similarly, marked increases in the phosphorylation of P38, c-Jun N-terminal kinase (JNK), and cleavage of caspase-3 by STZ were decreased significantly by co-treatment with 5 M -mangostin. These results suggest that -mangostin is capable of improving insulin secretion in pancreatic -cells and protecting cells from apoptotic damage.