Multi-target mechanism of triphala in cardio-cerebral vascular diseases based on network pharmacology

OBJECTIVE Numerous references made clear that triphala is revered as a multiuse therapeutic and perhaps even panacea historically. Nevertheless, the protective mechanism of triphala on cardio-cerebral vascular diseases(CCVDs) remains not comprehensive understanding. Hence, a network pharmacology-based method was suggested in this study to address this problem. METHODS This study was based on network pharmacology and bioinformatics analysis.Information on compounds in herbal medicines of triphala formula was acquired from public databases. Oral bioavailability as well as drug-likeness were screened by using absorption, distribution, metabolism, and excretion(ADME) criteria.Then, components of triphala, candidate targets of each component and known therapeutic targets of CCVDs were collected.Compound-target gene and compounds-CCVDs target networks were created through network pharmacology data sources. In addition, key targets and pathway enrichment were analyzed by STRING database and DAVID database.Moreover, we verified three of the key targets(PTGS2, MMP9 and IL-6) predicted by using Western blotting analysis.RESULTS Network analysis determined 132 compounds in three herbal medicines that were subjected to ADME screening, and 23 compounds as well as 65 genes formed the principal pathways linked to CCVDs. And 10 compounds,which actually linked to more than three genes, are determined as crucial chemicals. Core genes in this network were IL-6,TNF, VEGFA, PTGS2, CXCL8, TP53, CCL2, IL~(-1)0, MMP9 and SERPINE1. And pathways in cancer, TNF signaling pathway, neuroactive ligand-receptor interaction, etc. related to CCVDs were identified. In vitro experiments, the results indicated that compared with the control group(no treatment), PTGS2, MMP9 and IL-6 were up-regulated by treatment of10 μg·L~(-1) TNF-α, while pretreatment with 20-80 mg·L~(-1) triphala could significantly inhibit the expression of PTGS2,MMP9 and IL-6. With increasing Triphala concentration, the expression of PTGS2, MMP9 and IL-6 decreased. CONCLUSION Complex components and pharmacological mechanism of triphala, and obtained some potential therapeutic targets of CCVDs, which could provide theoretical basis for the research and development of new drugs for treating CCVDs.