Urolithin A, a pomegranate metabolite, protects pancreatic β Cells from apoptosis by activating autophagy
Urolithin A, a pomegranate metabolite, protects pancreatic β Cells from apoptosis by activating autophagy
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DOI：
10.1016/j.jep.2020.113628
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Gulimila Aisker
中科院分区：
文献类型：
--
作者：
YanZhi Zhang;Yan Zhang;Gulihaixia Halemahebai;Linai Tian;Huaiyang Dong;Gulimila Aisker
ABSTRACT .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 β-cells and the underlying .mechanisms. .Materials and methods: Apoptosis was induced in the pancreas of mice with type 2 .diabetes and MIN6 pancreatic β-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 β 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 β-cells by inducing activation of .autophagy
