Berberine Protects Pancreatic β-Cells From IL-1β Damage Through Hormetic Mechanisms Via P53-Mediated Apoptosis...

Damage to pancreatic β-cells serves as a critical pathological basis in the progression of diabetes. Berberine (BBR), an isoquinoline alkaloid, potentially protects pancreatic β-cells, exerting hypoglycemic effects. However, the dose-response relationship and the specific protective mechanism are still unclear. Hormesis is a self-protective response triggered by mild stimuli and has been reported to determine the extent to which phytochemicals can combat diabetes. In this study, we found that BBR exhibited a typical hormetic effect in IL-1β-induced damage to pancreatic β-cells, where low doses of BBR protect cells while high doses aggravate the damage. A model-based approach was used to describe dose-response relationships, as well as to detect and estimate hormetic effects. In addition, the regulatory effect of BBR in preventing apoptosis in pancreatic β-cells was confirmed, and an appropriate dose of BBR stabilized the mitochondrial membrane potential and prevented DNA damage. Moreover, the results showed that the hormetic effect of BBR was closely related to p53 and apoptosis pathways. To further investigate the role of the p53-mediated apoptosis pathways, our study interfered with the p53 pathway, resulting in the attenuation of the hormetic effect of BBR. These results introduce the concept of hormesis to study the biphasic effects of berberine on damaged pancreatic β-cells, while also exploring the relationship between the hormetic mechanism of BBR and the p53-mediated apoptosis pathway. These findings provide clues to explore the potential application of BBR in treating diabetes.