Polydatin enhances blood vessel relaxation and reduces NLRP3-mediated inflammation in hyperglycemia by lowering...

Polydatin, a natural component of Polygonum cuspidatum, exhibits potent anti-metabolic properties. The treatment with Poly (10 µm/L) effectively reversed the high glucose (HG)-induced reduction in acetylcholine (ACh)-elicited vasodilation in the aortas of Sprague-Dawley rats.

Male Sprague-Dawley rats were used to evaluate the effects of polydatin on endothelial function under HG conditions. Endothelium-dependent relaxation (EDR) was assessed in isolated thoracic aortic rings using ACh, with or without L-NAME or tempol. Human umbilical vein endothelial cells (HUVECs) were also treated under normal glucose (NG), HG, or HG + polydatin conditions. Gene expression (NLRP3, VCAM-1, GAPDH) was measured by RT-PCR, while protein levels of eNOS, iNOS, NLRP3, VCAM-1, and GAPDH were analyzed by western blotting.

HG significantly impaired ACh-induced EDR in rat aortic rings, while polydatin (10 µmol/L) restored vascular responsiveness. Mechanistically, polydatin upregulated eNOS and suppressed iNOS expression, and its vasoprotective effects were partially inhibited by L-NAME, indicating nitric oxide (NO) pathway involvement. In both aortic tissues and HUVECs, HG markedly increased NLRP3 and VCAM-1 expression, which was effectively reversed by polydatin, indicating its anti-inflammatory action.

Polydatin counteracts hyperglycemia-induced endothelial dysfunction by enhancing eNOS-dependent NO signaling to restore vasodilatory capacity, while inhibiting NLRP3 inflammasome activation and downstream VCAM-1 expression to attenuate vascular inflammation. These dual mechanisms position polydatin as a therapeutic agent for preserving vascular function in diabeticconditions.