Urolithin A protects pancreatic β Cells from apoptosis by activating autophagy. - GreenMedInfo Summary
Urolithin A, a pomegranate metabolite, protects pancreaticβ Cells from apoptosis by activating autophagy.
J Ethnopharmacol. 2020 Nov 24:113628. Epub 2020 Nov 24. PMID: 33246115
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 pancreaticβ-cells and the underlying mechanisms.
MATERIALS AND METHODS: Apoptosis was induced in the pancreas of mice with type 2 diabetes and MIN6 pancreaticβ-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 MIN6β 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 pancreaticβ-cells by inducing activation of autophagy.