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

作　　者：LIU Tian-long WANG Wen-jun WEN Ai-dong DING Yi 

机构地区：[1]Department of Pharmacy,Xijing Hospital,Fourth Military Medical University,Xi′an 710032,China [2]Department of Pharmacy,940 Hospital of PLA Joint Logistics Support Forces,Lanzhou 730050,China

出　　处：《中国药理学与毒理学杂志》2019年第9期740-741,共2页Chinese Journal of Pharmacology and Toxicology

基　　金：National Natural Science Foundation of China(81603385);China Postdoctoral Science Foundation(2018M643843);Natural Science Foundation of Shaanxi Province(2017JM8056);Key Research and Development Foundation of Shaanxi province(2018SF-241)

摘　　要：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-10,MMP9 and SERPINE1.And pathways in cancer,TNF signaling path⁃way,neuroactive ligand-receptor interaction,etc.related to CCVDs were identified.In vitro experiments,the results indi⁃cated that compared with the control group(no treatment),PTGS2,MMP9 and IL-6 were up-regulated by treatment of 10μg·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.CON⁃CLUSION Complex components and pharmacologicalOBJECTIVE 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-10, 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. C

关 键 词：TRIPHALA cardio-cerebral vascular diseases network pharmacology compound-target gene network 

分 类 号：R73[医药卫生—肿瘤]