Naoxintong capsules(脑心通胶囊)modulates tumor necrosis factor-α-induced endothelial senescence through silent information regulator 1 signaling

作者：GUO Qianyun; ZHANG Bin; ZHANG Haitong; ZHANG Erli; WU Yongjian

来源：Journal of Traditional Chinese Medicine, 2021, 41(02): 212-218.

• tumor necrosis factor-alpha
• sirtuin 1
• forkhead box protein O1
• Naoxintong

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.

• 单位
  心血管疾病国家重点实验室; 北京协和医学院; 中国医学科学院北京协和医院