Centaurium erythraea extract mediates prosurvival pathways and insulin expression in STZ-treated beta-cells

Abstract

Diabetes is characterized by hyperglycaemia resulting from a deficiency in insulin secretion and/or action leading to severe diabetic complications. Despite numerous efforts, recovery and maintenance of functional beta-cells is still an unresolved task in diabetes therapy. Considering anti-diabetic properties of medicinal herb Centaurium erythraea Rafn (CE), this study aimed to analyze protective effects of the CE extract on Rin-5F beta-cell line exposed to diabetogenic agent streptozotocin (STZ). Cytoprotective concentration of CE extract (0.25 mg/mL) and IC50 dose of STZ (12mM) were determined using cell viability assay (MTT). The level of insulin mRNA and the concentration of insulin released from beta-cells in a culture medium were analyzed by RT-qPCR and ELISA, respectively. Activity of Akt, ERK and p38 kinases, as well as nuclear levels of islet-enriched Pdx1 and MafA proteins were assessed by Western blot analysis. In comparison to STZ-treated cells, CE extract/STZ co-treatment increased viability of Rin- 5F cells for 12%. STZ-treated beta-cells displayed reduced mRNA level of insulin to 63% and reduced insulin secretion to 76% in comparison to controls, while application of CE extract improved insulin mRNA level to 77% and insulin secretion to 90% of the control level. Improved viability and functionality of beta-cells could be ascribed to a CE extractmediated modulation of the activities of pro-survival Akt, ERK and p38 kinases and Pdx- 1 and MafA factors involved in regulation of beta-cell proliferation and insulin expression/secretion. The results of this study suggest that CE extract promotes proliferative and pro-survival pathways in beta-cells and improves their functional properties