Liuwei Dihuang Prevents Human Umbilical Vein Endothelial Cells Senescence via the JPX-STING-IRF3 Pathway.

Abstract

Cellular senescence plays a crucial role in age-related diseases. Endothelial senescence is closely associated with age-related vascular disorders. This study aimed to reveal the role of traditional Chinese medicine Liuwei Dihuang (LWDH) in anti-endothelial cell senescence. Human umbilical vein endothelial cells (HUVECs) were exposed to LPS treatment to induce senescence. Senescence-associated β-galactosidase (SA-β-gal) positive staining, p53 and p16 expression, BrdU staining, and relative telomere length (RTL) experiments were conducted to estimate LPS-induced cellular senescence of HUVECs. Real-time qPCR analysis was performed to identify differentially expressed lncRNAs in LPS-induced senescent HUVECs before and after treatment with LWDH. Bioinformatics analysis and ChIP assay were conducted to explore the mechanism of JPX in the anti-endothelial cell aging effect of LWDH. We first discovered that lncRNA JPX and STING-IRF3 pathways are involved in the process of anti-endothelial senescence of LWDH. Mechanistically, LWDH could reverse abnormally elevated JPX induced by LPS and inhibit the activation of STING, as well as the interaction between JPX and STING. Overall, our study explores the potential therapeutic value of LWDH and provides key insights into the potential avenues for preventing and treating HUVECs senescence.