Puerarin mitigated LPS‐ATP or HG‐primed endothelial cells damage and diabetes‐associated cardiovascular disease via ROS‐NLRP3 signalling

Abstract

AbstractThe occurrence and development of diabetic vascular diseases are closely linked to inflammation‐induced endothelial dysfunction. Puerarin (Pue), the primary component of Pueraria lobata, possesses potent anti‐inflammatory properties. However, its vasoprotective role remains elusive. Therefore, we investigated whether Pue can effectively protect against vascular damage induced by diabetes. In the study, Pue ameliorated lipopolysaccharide‐adenosine triphosphate (LPS‐ATP) or HG‐primed cytotoxicity and apoptosis, while inhibited reactive oxygen species (ROS)‐mediated NLR family pyrin domain containing 3 (NLRP3) inflammasome in HUVECs, as evidenced by significantly decreased ROS level, NOX4, Caspase‐1 activity and expression of NLRP3, GSDMD, cleaved caspase‐1, IL‐1β and IL‐18. Meanwhile, ROS inducer CoCI2 efficiently weakened the effects of Pue against LPS‐ATP‐primed pyroptosis. In addition, NLRP3 knockdown notably enhanced Pue's ability to suppress pyroptosis in LPS‐ATP‐primed HUVECs, whereas overexpression of NLRP3 reversed the inhibitory effects of Pue. Furthermore, Pue inhibited the expression of ROS and NLRP3 inflammasome‐associated proteins on the aorta in type 2 diabetes mellitus rats. Our findings indicated that Pue might ameliorate LPS‐ATP or HG‐primed damage in HUVECs by inactivating the ROS‐NLRP3 signalling pathway.