Protective Effects of Hyperoside on Type 2 Diabetes Through the Regulation of Pancreatic β-cell Function

Type 2 diabetes mellitus (T2D) is a prevalent chronic disease characterized by pancreatic β-cell loss induced by hyperglycemia. Effective treatments to repair β-cell damage remain unclear. Hyperoside, a flavonoid glycoside with diverse pharmacological effects, has rarely been studied in H₂O₂-induced β-cell injury, and its mechanisms are unknown.

To explore the protective effects of hyperoside on H₂O₂-induced pancreatic β-cell damage and its underlying mechanisms.

RIN-m5F cells were pretreated with 0, 25, 50, 100 μM hyperoside or 5 μM ML385 (inhibitor of the Nrf2/HO-1 pathway) for 48 h, followed by 100 μmol/ml H₂O₂ for another 30 min. MTT assay and flow cytometry were used to assess cell viability and apoptotic cells. The activities of ROS, CAT, SOD, GSH-PX, and MDA were measured using the corresponding assay kits. The levels of apoptosis-related proteins, including cleaved-caspase3 and caspase-3, were determined by western blotting. A glucose-stimulated insulin secretion (GSIS) assay was used to assess insulin secretion. Reverse-transcription quantitative PCR (RT-qPCR) and western blotting were used to measure the expression of Nrf2 and HO-1 in the Nrf2/HO-1 pathway.

Hyperoside (0, 25, 50, 100 μM) showed no toxic side effects on RIN-m5F cells. H₂O₂ reduced RIN-m5F cell viability, increased apoptosis, elevated ROS/MDA, decreased antioxidant enzyme activities, suppressed insulin secretion, and downregulated Nrf2/HO-1. Hyperoside pretreatment reversed these effects, improving viability, reducing apoptosis, restoring antioxidant activity, enhancing insulin secretion, and upregulating Nrf2/HO-1. ML385 abolished hyperoside's protective effects.

Hyperoside protects pancreatic β-cells against oxidative stress and apoptosis by activating the Nrf2/HO-1 pathway. It may serve as a potential therapeutic agent for preventing β-cell damage in T2D.