Prunetin Attenuates Dexamethasone-Induced Pancreatic β-Cell Apoptosis: Modulation of Oxidative Stress and MAPK...

Dexamethasone has been reported to induce pancreatic β-cell apoptosis, which may contribute to steroid-induced diabetes following long-term glucocorticoid therapy. Although prunetin, a natural isoflavone, has been shown to attenuate dexamethasone-induced pancreatic β-cell apoptosis with suppression of p53 signaling as an associated pathway, the involvement of other signaling pathways remains unclear. This study aimed to investigate whether prunetin-mediated attenuation of dexamethasone-induced β-cell apoptosis was associated with changes in phosphorylated c-Abl (p-c-Abl) levels, oxidative stress, and MAPK signaling pathways. The rat insulinoma cell line INS-1 was treated with dexamethasone in the presence or absence of prunetin, followed by Annexin V-FITC/propidium iodide staining, western blotting, superoxide measurement, and caspase-3/7 activity assays. Dexamethasone induced early apoptosis, reduced p-c-Abl and glutathione S-transferase P1 (GSTP1) levels, increased superoxide generation, elevated phosphorylated JNK and p38 levels, decreased phosphorylated ERK1/2 levels, and stimulated caspase-3/7 activity, whereas total c-Abl levels remained unchanged. Prunetin pre-treatment before dexamethasone administration significantly reduced early apoptosis, restored GSTP1 expression, attenuated oxidative stress, and modulated MAPK signaling by decreasing phosphorylated JNK and p38 levels while increasing phosphorylated ERK1/2 levels. However, prunetin did not restore the dexamethasone-induced reduction in p-c-Abl levels. These findings suggest that prunetin attenuates β-cell apoptosis induced by dexamethasone and that this effect is associated with modulation of oxidative stress, GSTP1 expression, and MAPK signaling pathways, but not with restoration of reduced p-c-Abl levels. Collectively, this study extends current knowledge of signaling changes associated with prunetin in glucocorticoid-induced β-cell injury.