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

Abstract

Background and aims: 2,3,5,4'-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 results: Oral 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 H(2)O(2)-induced cellular senescence and K373 acetylation of p53 in cultured human umbilical vein endothelial cells (HUVECs).

Conclusions: THSG 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.