Pterostilbene Inhibits Diabetes: Suppression of Islet Cell Apoptosis
Therapeutic potential of pterostilbene against pancreatic beta-cell apoptosis mediated through Nrf2
Immunoblotting and quantitative reverse transcriptase (qRT)-PCR analysis were performed to identify PTS-mediated nuclear translocation of Nrf2 protein and the following activation of target gene expression, respectively, in INS-1E cells. In addition, an annexin-V binding assay was carried out to identify the apoptotic status of PTS-treated INS-1E cells, while confirming the anti-apoptotic potential of Nrf2 by qRT-PCR analysis of the expressions of both pro-and anti-apoptotic genes.
PTS induced significant activation of Nrf2, in dose-and time-dependent manner, in streptozotocin-treated INS-1E rat pancreatic beta-cells. Furthermore, PTS increased the expression of target genes downstream of Nrf2, such as heme oxygenase 1 (HO1), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), that confer cellular protection. PTS also up-regulated the expression of anti-apoptotic gene, Bcl-2, with a concomitant reduction in pro-apoptotic Bax and caspase-3 expression.
Conclusion and Implications
Collectively, our findings indicate the therapeutic potential of Nrf2 activation by PTS as a promising approach to safeguard pancreatic beta-cells against oxidative damage in diabetes.