2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside ameliorates vascular senescence and improves blood flow involving a mechanism of p53 deacetylation

Background and aims2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (THSG), a resveratrol analog with glucoside, has been shown in various studies to inhibit proliferation of vascular smooth muscle cells, attenuate inflammation, and prevent vascular endothelial dysfunction. In the study, we examined the effects of THSG on vascular senescence and blood flow.Methods and resultsOral administration of THSG for 14 weeks, resulted in notable increases in blood flow in spontaneously hypertensive rats (SHRs); and effective inhibition of vascular senescence as indicated by senescence-associated β-galactosidase (SA-β-gal) staining, phosphorylation of γH2AX observed by stain analysis of immunofluorescence, and K373 acetylation of p53 in the aortic arches of SHRs. Oral administration of THSG also induced eNOS expression and urinary NOx production. THSG weekly activated SIRT1 activity, stimulated eNOS promoter reporter gene activity, and ameliorated H2O2-induced cellular senescence and K373 acetylation of p53 in cultured human umbilical vein endothelial cells (HUVECs).ConclusionsTHSG improves blood flow and ameliorates vascular senescence by increasing eNOS expression and Sirt1 activity and decreasing acetylation of p53 at K373 site, at least in part, both in vitro and in vivo.

► Stilbene from Chinese medical herb ameliorated vascular senescence. ► The compound induced eNOS expression in reporter gene and mRNA from aortas. ► Oral administration in long-term obviously improved the blood flow in SHR. ► The resveratrol analog is a weak activator of SirT1 by activity assay. ► The mechanism involves p53 deacetylation in the aortic arches.