The pathogenesis of diabetes is associated with dysfunction of pancreatic β-cells. To ameliorate the β-cell dysfunction, it has propelled great interest to search pharmacological agents from natural plants. This study explored the protective effect of apigetrin, a flavonoid present in natural plants, against streptozotocin (STZ)-induced cell damages in RINm5F cells and the potential mechanisms. Apigetrin was found to inhibit the elevation of intracellular reactive oxygen species levels, restore the impairment of antioxidant enzymes, and recover the disruption of redox homeostasis in the STZ-treated pancreatic β-cells. Moreover, treatment of apigetrin significantly suppressed the STZ-induced apoptosis in the analysis of apoptotic sub-G₁ population and the protein expressions of cleaved poly(ADP-ribose) polymerase and caspase-3. Furthermore, apigetrin attenuated STZ-induced endoplasmic reticulum (ER) stress, indicated by the reduction of ER stress biomarkers, including overloading of mitochondrial calcium, increase in glucose-regulated protein 78, phosphorylation of protein kinase RNA-like ER kinase and its downstream eukaryotic initiation factor 2α, cleavage of activating transcription factor 6 and caspase-12, up-regulation of CCAAT/enhancer binding protein homologous protein, and induction of spliced X-box binding protein 1. Additionally, pretreatment with 4-phenylbutyric acid, a classic ER stress inhibitor, augmented these beneficial effects of apigetrin. In conclusion, these results demonstrated that apigetrin could improve the STZ-induced pancreatic β-cell damages via mitigation of oxidative stress and ER stress and supported the application of apigetrin to developing the novel therapeutics of diabetes.

糖尿病的发病机制与胰腺β细胞功能障碍有关。为改善β细胞功能障碍，它引起了人们对从天然植物中寻找药理学剂的兴趣。这项研究探索了天然植物中存在的类黄酮芹菜素对链脲佐菌素（STZ）诱导的RINm5F细胞损伤的保护作用及其潜在机制。发现芹菜素抑制STZ处理的胰腺β细胞中细胞内活性氧水平的升高，恢复抗氧化酶的损伤，并恢复氧化还原稳态的破坏。此外，在凋亡亚G ₁的分析中，芹菜素的治疗显着抑制了STZ诱导的细胞凋亡。聚（ADP-核糖）聚合酶和caspase-3酶切蛋白的表达及蛋白表达 此外，apigetrin可减轻STZ诱导的内质网（ER）应激，其表现为ER应激生物标志物的减少，包括线粒体钙超载，葡萄糖调节蛋白78的增加，蛋白激酶RNA样ER激酶的磷酸化及其下游的真核生物起始因子2α，激活转录因子6和caspase-12的裂解，CCAAT /增强子结合蛋白同源蛋白的上调，以及剪接的X-box结合蛋白1的诱导。此外，还用4-苯基丁酸（一种经典的ER）进行预处理压力抑制剂，增强了apigetrin的这些有益作用。结论，