Nuciferine attenuates uric acid-induced apoptosis in HUVECs via regulation of the SIRT6/ROS signaling pathway.

BACKGROUND

Nuciferine, a constituent of lotus leaf, has a potentially beneficial effect for cardiovascular disease therapy. Sirtuin6 (SIRT6) is a component of the class III histone deacetylase group that depends on NAD+ and has an important function in the modulation of cardiovascular diseases. The objective of this research was designed to assess the protective impact of nuciferine in safeguarding human umbilical vein endothelial cells (HUVECs) from apoptosis and the mechanisms involved.

METHODS AND

RESULTS

In uric acid (UA)-stimulated HUVECs, nuciferine increased cell viability and nitric oxide level. UA increased the apoptosis of HUVECs. Nuciferine inhibited apoptotic cell percentage and Bax/Bcl-2 ratio as well as expression of cleaved caspase-3 protein and caspase-3 activity. Moreover, nuciferine increased the SIRT6 expression in HUVECs exposed to UA. Significantly, the silencing of SIRT6 negated the protective effect of nuciferine on the apoptosis of HUVECs. Additional investigations indicated that nuciferine also reduced the reactive oxygen species (ROS) generation in HUVECs. Furthermore, nuciferine exerted a suppressive impact on HUVECs apoptosis, which was partially mediated by the reduction of ROS.

CONCLUSIONS

Collectively, our data suggest that nuciferine can regulate the apoptosis in HUVECs, potentially through mechanisms involving SIRT6 and ROS.