Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3

Abstract

Objective To investigate the inhibitory effects and mechanism of dihydromyricetin (DHM) on the activation of NLRP3 inflammasome and improvement of palmitic acid induced injury in vascular endothelial cells through Sirtuin 3(Sirt3). Methods Human umbilical vein endothelial cells (HUVECs) were treated with palmitic acid (200 μmol/L) to establish an inflammatory injury model, which was subsequently intervened with different concentrations of DHM (10, 20 and 40 μmol/L).Cell viability, LDH release level and expression of endothelial cell adhesion factors were detected respectively.qRT-PCR and Western blotting were used to measure the mRNA and protein levels of cytokines related to NLRP3 inflammasome activation.The regulatory effects of DHM on mitochondrial function of endothelial cells were determined by Seahorse Extracellular Flux Platform and mitochondrial membrane potential assay.Moreover, Sirt3-specific inhibitor 3-TYP (50 μmol/L) and Sirt3 overexpression plasmid were adopted to explore the role of Sirt3 in DHM inhibiting the activation of NLRP3 inflammasome induced by palmitic acid. Results DHM significantly inhibited the decline in cell viability, release of LDH, and secretion of endothelial cell adhesion factors ICAM-1 and VCAM-1 induced by palmitic acid (P < 0.05).Moreover, DHM remarkably improved the decrease of oxygen consumption for mitochondrial respiratory activity, enhanced ATP production and residual respiratory capacity, and suppressed the elevation of mitochondrial membrane potential (P < 0.05).Meanwhile, DHM also suppressed the mRNA and protein levels of NLRP3, IL-18 and ASC induced by palmitic acid (P < 0.05).Sirt3 overexpression enhanced the above effects of DHM, while the Sirt3 inhibitor 3-TYP obviously attenuated these effects. Conclusion DHM maintains mitochondrial metabolism of endothelial cells by activating Sirt3, inhibits the activation of NLRP3 inflammasome, and thus alleviates the inflammatory damage in HUVECs. [Key words] dihydromyricetin , vascular endothelial cells , atherosclerosis , NLRP3 inflammasome , Sirt3 ,

Keywords

• dihydromyricetin
• vascular endothelial cells
• atherosclerosis
• nlrp3 inflammasome
• sirt3