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Objective To explore the regulatory effect of hypericin targeting Nrf2/HO-1 pathway on pancreatic beta cell function in Type 2 diabetes and its potential molecular mechanism. Methods Induced oxidative damage in rat pancreatic beta cell line RIN-m5F by hydrogen peroxide$\left({{\mathrm{H}}_{2}{\mathrm{O}}_{2}}\right)$, pancreatic beta cells were treated with 0,25,50, and 100$\mu$M hyperoside and ML385 (Nrf2 inhibitor). Real time fluorescence quantitative PCR (RT-qPCR) was used to evaluate Nrf2 and HO-1, protein imprinting was used to detect cleaved-Caspase3 and Caspase3, and glucose stimulated insulin secretion assay, 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyltetrazolium bromide thiazole blue, tetrazolium tetrazolium salt (MTT), flow cytometry, and oxidative stress assay kit were used to detect insulin, cell viability, apoptosis, and oxidative stress in rat pancreatic beta cell line RIN-m5F. Results A certain concentration of hyperoside had no cytotoxic effect on RIN-m5F pancreatic beta cells and increased cell survival rate. Hypericin dose dependently reduced apoptosis rate, reactive oxygen species (ROS), and malondialdehyde (MDA) levels, while increasing catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and insulin levels. With the dose-dependent increase of hyperoside, the level of cleaved-Caspase3 significantly decreased, the ratio of cleaved-Caspase3/Caspase3 significantly decreased, and the expression levels of Nrf2 and HO-1 significantly increased. After the addition of Nrf2 inhibitor ML385, the overall expression level decreased, with the same trend as before. Hypericin can activate the levels of antioxidant response elements (ARE) and heat shock protein (HSP90 α), indicating that it can initiate the transcription of a series of antioxidant genes and regulate antioxidant responses. Conclusion Hyperin plays a protective role in Type 2 diabetes islet beta cells by activating Nrf2/HO-1/ARE pathway, and improves the function of islet beta cells.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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