OBJECTIVE:To investigate the protective effects of Naoxintong capsules(脑心通胶囊,NXT)on tumor necrosis factor-α(TNF-α)-induced senescence inen-dothelial cells and its mechanism.METHODS:Human umbilical vascular endothelial cells(HUVECs)were treated with TNF-α±NXT and assessed for silent information regulator 1(SIRT1)expression and signaling.Cells were stained with beta-galactosidase to assess the levels of cellular se-nescence.SIRT1 was silenced through siRNA trans-fection.RESULTS:TNF-α treatment led to the downregula-tion of SIRT1,resulting in forkhead box O1(FoxO-1)acetylation,p53 acetylation and enhanced p21 ex-pression.Following TNF-α treatment,higher Saβ-Gal activity improved.TNF-α enhanced the migra-tion of HUVECs and increased SIRT1 expression,both of which were attenuated by NXT treatment.The downstream targets of SIRT1 including FoxO-1/p53/p21 were also modulated,and HUVECs were protected from TNF-α-induced senescence.In con-trast,the NXT-mediated protection was prevented by SIRT1 silencing.CONCLUSIONS:These findings suggest that sus-tained endothelial senescence can be induced by TNF-α stimulation via the SIRT1/FoxO-1/p53/p21 pathway.The protection of NXT against TNF-α was partially mediated through its effects on SIRT1.This highlights the promise of NXT as a therapeutic for atherosclerosis.