Ginseng-Sanqi-Chuanxiong extract ameliorates hypertensive vascular aging through endothelial–smooth muscle cell crosstalk via the PPARγ/NF-κB axis

Background Vascular aging is an important pathological basis of hypertension and hypertension-associated target-organ injury. Ginseng-Sanqi-Chuanxiong (GSC) extract has been shown to have protective effects against vascular dysfunction; however, its mechanisms in hypertensive vascular aging remain unclear. Objective In this study, we investigated the protective effects and mechanisms of GSC in hypertensive vascular aging. Materials and Methods The chemical compounds present in GSC decoction were identified through ultra-performance liquid chromatography–quadrupole time-of-flight–mass spectrometry with elevated energy data acquisition (UPLC-Q-TOF/MS E ) analysis. Network pharmacology was then used to predict the potential targets and signaling pathways. Ten-month-old spontaneously hypertensive rats (SHRs) were treated with GSC for 4 months to evaluate vascular aging and target-organ injury. Lastly, endothelial–smooth muscle cell (EC-SMC) co-culture, molecular docking, and surface plasmon resonance (SPR) assays were used to investigate the underlying mechanisms. Results UPLC-Q-TOF/MS E helped identify 55 compounds in GSC that were predominantly saponins, lactones, and phenolic-related constituents. Network pharmacology analysis suggested that PPARγ/NF-κB signaling could be a core regulatory pathway. GSC treatment reduced the systolic blood pressure while attenuating cardiac hypertrophy and fibrosis, renal glomerular sclerosis and tubular injury, and hippocampal neuronal loss in the SHRs. GSC also alleviated vascular remodeling, vascular stiffness, and vascular senescence while decreasing inflammatory cytokine and senescence-related protein expression levels and regulating PPARγ/NF-κB signaling in vascular tissues. In the EC-SMC co-culture system, GSC intervention attenuated senescence in Ang-II-induced endothelial cells and inflammatory responses in co-cultured smooth muscle cells through endothelial-mediated paracrine regulation. The molecular docking and SPR assays further demonstrated direct interactions between PPARγ and GSC constituents, including kaempferol, senkyunolide H, and levistolide A. Conclusion GSC attenuated hypertensive vascular aging through its protective effects associated with endothelial-mediated regulation of the PPARγ/NF-κB signaling pathway, providing scientific evidence of the vascular protective effects of GSC in hypertension.