Artesunate protects pancreatic ß-cells from streptozotocin-induced diabetes via inhibition of the NLRP3/caspase-1/GSDMD pathway.

ABSTRACT

BACKGROUND: Reports in recent years have shown that pancreatic ß-cell pyroptosis represents a critical mechanism involved with the progressive failure of pancreatic function. Previous research from our laboratory has indicated that artemether can increase the number of cells in pancreatic islets of db/db mice. In this study, we further examined whether artesunate (ART) protects pancreatic ß-cells from the damage of streptozotocin (STZ) by inhibiting pyroptosis. MATERIALS AND METHODS: In vitro, MIN6 cells exposed to 1 mM STZ were treated with ART (0.8 or 1.6 µM). The effects of ART on STZ-treated cells were evaluated through CCK-8 assay, flow cytometry and western blot, and further compared the effects of ART with the NLRP3 inhibitor, Mcc950 upon pyroptosis pathway proteins using western blot. In vivo, Male C57 mice were administered with a single intraperitoneal injection of STZ, and those with confirmed diabetes mellitus were given ART (0.5 or 1.0 mg/ml in drinking water) for 18 days. The effects of ART on STZ-induced diabetes were assessed by the observation of the general situation, glucose tolerance test, hematoxylin-eosin (HE) staining and immunohistochemistry. RESULTS: In MIN6 cells treated with STZ, we found that ART increased cell viability, decreased the number of late apoptotic cells (including pyroptosis cells) and inhibited the expression of proteins associated with the pyroptosis pathway. In STZ-induced animal model, the administration of ART reduced blood glucose levels, improved the consumption status within this diabetic mouse model and inhibited the expression of proteins include in the pyroptosis pathway in mice pancreats. CONCLUSIONS: Inhibition of pyroptosis may be a critical mechanism through which artesunate exerts protective effects upon pancreatic ß cells.