9-Hydroxy-6,7-dimethoxydalbergiquinol suppresses hydrogen peroxide-induced senescence in human dermal fibroblasts through induction of sirtuin-1 expression

摘要

Objective:To investigate the potential anti-aging mechanism of9-hydroxy-6,7-dimethoxydalbergiquinol(HDDQ)on hydrogen peroxide(H2O2)-induced oxidative stress in human dermal fibroblasts(HDFs).Methods:The effect of HDDQ on cell viability was assessed by MTT assay,and the effects of HDDQ on senescence-like phenotypes were determined by senescence-associatedβ-galactosidase(SA-β-gal)staining,Western blotting analysis,and a cell proliferation assay.The expression level and activity of sirtuin-1(SIRT1)induced by HDDQ were also measured.Results:HDDQ reversed senescence-like phenotypes in the oxidant-challenged model,through reducing SA-β-gal activity and promoting cell growth.Meanwhile,decreases in ac-p53,p21Cip1/WAF1,and p16Ink4a and an increase in p Rb were observed.HDDQ induced the expression of SIRT1 in a concentration-and time-dependent manner.Moreover,HDDQ inhibited H2O2-induced phosphorylation of Akt by SIRT1 up-regulation and reduced SA-β-gal staining.Conclusions:HDDQ inhibits H2O2-induced premature senescence and upregulation of SIRT1 expression plays a vital role in the inhibition of the senescence phenotype in HDFs.