Protective effect of different flavonoids against endothelial senescence via NLRP3 inflammasome

Senescence of vascular endothelial cells promotes endothelial dysfunction and contributes to the progression of cardiovascular diseases. It is imperative to explore effective methods to suppress endothelial senescence. Herein, we found flavonoids including quercetin, puerarin and troxerutin, which exist in normal diet and extracted from traditional herbs, delayed d-glucose-induced endothelial senescence and restored endothelial functions. In the process, d-glucose amplified endogenous reactive oxygen species (ROS) level and subsequently promoted NLRP3 inflammasome activation. However, these alterations were reversed by flavonoids. Meanwhile, clearance of ROS or interference of NLRP3 function by specific siRNA attenuated high glucose-induced senescence but advanced the anti-senescent impact of flavonoids. On the contrary, the preventive effect of flavonoids on senescence was disturbed once NLRP3 inflammasome was overactivated. Our studies suggest that flavonoids can inhibit high glucose-induced endothelial premature senescence by suppressing NLRP3 inflammasome activity, which may be a useful therapeutic strategy to alleviate endothelial senescence-related vascular diseases.