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Urolithin A, a pomegranate metabolite, protects pancreatic beta cells from apoptosis by activating autophagy

作者 Zhang, YanZhi; Zhang, Yan; Halemahebai, Gulihaixia; Tian, Linai; Dong, Huaiyang; Aisker, Gulimila

期刊 JOURNAL OF ETHNOPHARMACOLOGY , MAY 23 2021,:272

DOI 10.1016/j.jep.2020.113628 PubMed 33246115

摘要 Ethnopharmacological relevance: Urolithin A is an active metabolite of plant polyphenol ellagic acid generated by intestinal flora, which is derived from strawberry or traditional anti-diabetic Chinese medicine such as Punica granatum L. and Phyllanthus emblica. The present study aimed to whether urolithin A can protect against glycolipid-toxicity-induced apoptosis of pancreatic beta-cells and the underlying mechanisms.Materials and methods: Apoptosis was induced in the pancreas of mice with type 2 diabetes and MIN6 pancreatic beta-cells. CC-8 assay was conducted to determine cell viability. Flow cytometry, JC-1 fluorescent probe, and western blot assays were performed to assess apoptosis. Immunofluorescence and western blot assays were used to detect changes in autophagy. The mechanism of apoptosis was elucidated using autophagy inhibitor chloroquine.Results: Urolithin A intervention significantly reduced pancreatic cell apoptosis in diabetic mice and MIN6 p cells. This was achieved by the downregulation of cleaved-caspase 3, cleaved-caspase 1, and restoration of cell viability, cell morphology and mitochondrial membrane potential, accompanied with the downregulation of autophagic protein SQSTM1/p62 and upregulation of LC3II. Chloroquine, an autophagy inhibitor, reversed the anti-glucolipotoxic and anti-apoptotic effects of urolithin A.Conclusion: These findings suggest that urolithin A protects against glucolipotoxicity-induced apoptosis in pancreatic beta-cells by inducing activation of autophagy.

涉及物种 余甘子 Phyllanthus emblica 石榴 Punica granatum