Integrating systematic pharmacology-based strategy and experimental validation to explore the synergistic pharmacological mechanisms of Guanxin V in treating ventricular remodeling.

Abstract Background Guanxin V (GXV) has been widely used to treat ventricular remodeling (VR) in clinical practice in China. However, the underlying mechanisms are currently still lack. Methods A systematic pharmacology-based strategy was utilized for predicting the synergistic pharmacological mechanisms of GXV in VR. The active compounds of GXV were selected and then the potential targets of these compounds contained in GXV and VR were successively identified. Then, after networks were constructed, DAVID was applied to functional enrichment. Moreover, the key findings were validated though molecular docking and molecular biology experiments. Results A total of 119 active components in GXV and 169 potential targets shared between GXV and VR were obtained. The results of functional enrichment indicated that several biological processes and signaling pathways, mainly cell apoptosis and fibrosis. Finally, we discovered GXV produced marked anti-apoptosis and anti-fibrosis effects in VR though Caspase-3 and TGF-β1. Conclusion GXV could relieve and reverse VR through anti-apoptosis and anti-fibrosis effects predicted by systematic pharmacology and validated by molecular docking and molecular experiments. Our study deepens the understanding of the molecular mechanisms of GXV in treating VR.