Ameliorative effects of hispidulin on high glucose-mediated endothelial dysfunction via inhibition of PKCβII-associated NLRP3 inflammasome activation and NF-κB signaling in endothelial cells

Abstract

Endothelial dysfunction is closely relevant to atherosclerosis complications in diabetic patients. Hispidulin, a flavone derived from the herb Salvia plebeia R. Br., has numerous biological properties including anti-inflammatory and antioxidative effects, but the underlying mechanism of its anti-inflammatory action remains unclear. This study was designed to investigate the effects of hispidulin on endothelial homeostasis and its mechanism. Hispidulin effectively inhibited high glucose-induced oxidative stress by attenuating PKCβII phosphorylation and downstream reactive oxygen species (ROS) production, furthermore reversing the loss of mitochondria membrane potential. Moreover, hispidulin significantly suppressed the expression of NLRP3 inflammasome and IKKβ/NF-κB, and restored high glucose-impaired vasodilation in rat aorta. This study demonstrated that hispidulin ameliorated high glucose-mediated endothelial dysfunction via inhibiting PKCβII-associated NLRP3 inflammasome activation and NF-κB signaling. Besides, these findings indicate the beneficial effects of hispidulin on the improvement of endothelial dysfunction and explain its potential application in the prevention and treatment of diabetic vascular complications.

Keywords

• Hispidulin
• Endothelial dysfunction
• PKCβII
• NLRP3 inflammasome
• Oxidative stress
• High glucose