Abstract: OBJECTIVE: To investigate the protective effects of Naoxintong capsules(脑心通胶囊, NXT)on tumor necrosis factor-α(TNF-α)-induced senescence inendothelial 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 senescence. SIRT1 was silenced through si RNA transfection.RESULTS: TNF-α treatment led to the downregulation of SIRT1, resulting in forkhead box O1(FoxO-1)acetylation, p53 acetylation and enhanced p21 expression. Following TNF-α treatment, higher SAβ-Gal activity improved. TNF-α enhanced the migration 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 contrast, the NXT-mediated protection was prevented by SIRT1 silencing.CONCLUSIONS: These findings suggest that sustained 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.

Key words: tumor necrosis factor-alpha;;sirtuin 1;;forkhead box protein O1;;Naoxintong