Deciphering the anti-atherosclerotic mechanisms of Danggui-Chuanxiong herb pair: a synergistic approach combining computational prediction and in vivo verification

Introduction Danggui-Chuanxiong is a classic Chinese medicine formulation clinically employed for atherosclerosis (AS) management by modulating lipid metabolism and improving hemodynamic properties. Materials and methods Integrated network pharmacology, molecular docking and molecular dynamics simulation approaches were employed to elucidate the material basis and therapeutic mechanisms of DG-CX in AS treatment, and validated by subsequent experiments. The regulatory effects of DG-CX on the c-Abl/YAP signaling pathway were comprehensively assessed through integrated histopathological and molecular analyses. Results Network pharmacology analysis identified sterols, stigmasterol, and wallichilide as the principal bioactive constituents of DG-CX. Furthermore, molecular docking validated that VEGFR2 and PTGS2 are the core targets, which are potentially mediated through c-Abl/YAP signaling pathway, consistent with strong binding affinities. Molecular dynamics simulations of the protein-ligand complexes revealed that the PTGS2-FER and VEGFR2-β-sitosterol complexes exhibited stable binding, with favorable hydrogen bonding interactions. Our research results show that DG-CX can reduce the body weight of AS mice, improve lipid metabolism disorders, and upregulate the expression of NO/NOS, AngII/AT1R, and PGI2 ( p < 0.01), inhibit the expression of VEGFR2 and PTGS2 mRNA ( p < 0.05 or p < 0.01), and the expression of the Interα5β1/c-Abl/YAP pathway. Conclusions Validation using network pharmacology, molecular docking, molecular dynamics simulation and in vivo studies suggested the efficacy of DG-CX in improving vascular endothelial function and exerting anti-AS effects by inhibiting the c-Abl/YAP signaling pathway.