Objective: To evaluate the efficacy of Renshen Sanqi Chuanxiong formula (RSCF) for preventing vascular aging, and to investigate the possible molecular mechanism underlying the actions of RSCF.
Methods: Potentially active components and their relatively direct targets were identified by combining drug-likeness (DL) screening using a target identification process. Vascular aging-associated targets for RSCF were obtained by selecting common genes not only from potential targets but also from human vascular aging-associated genes. Cytoscape 3.2.1 software was employed to visualize the complex compound-target and target-function networks. Biological process and molecular function were assessed, and the Kyoto Encyclopedia of Genes and Genomes and pathway enrichment analyses were performed using ClueGO. Pathways directly associated with vascular aging were integrated into a ""vascular aging-related"" pathway.
Results: Altogether, 122 potentially active components of RSCF were identified through DL screening, and their corresponding 692 direct targets were retrieved via target prediction and identification. We identified 49 vascular aging-associated targets for RSCF by overlapping the 692 potential targets with 146 human vascular aging-associated genes. The results from the compound-target network indicated that most components acted on common targets and displayed synergistic action, which showed that the magnifying effects of RSCF were based on these common targets. The target-function network revealed that each target was involved in multiple function modules, suggesting that RSCF was multi-functional during treatment of vascular aging. The results of the ClueGO analysis indicated that most of the targets were associated with the hypoxia-inducible factor 1 (HIF-1) signaling pathway. The results from the pathway analysis also indicated that an integrative vascular aging-related pathway mainly included an angiogenesis regulation module, cell-survival module, and oxidative stress-resistance module.
Conclusion: Our results suggested that many components act synergistically on common targets to delay vascular aging, and each target is involved in multiple functional modules. The ClueGO analysis indicated that most of the targets were connected to the HIF-1 signaling pathway, FOXO signaling pathway, and thyroid hormone signaling pathway.
Keywords: Cardiovascular diseases; Drug development; Molecular mechanism; Pharmacology; Renshen Sanqi Chuanxiong formula; Vascular aging.