Objective:To identify the secondary metabolites of Hei-Yun-Xiang(黑云香),predict its target by network pharmacology,and the target binding activity was demonstrated by molecular docking to explore its mechanism in tre...Objective:To identify the secondary metabolites of Hei-Yun-Xiang(黑云香),predict its target by network pharmacology,and the target binding activity was demonstrated by molecular docking to explore its mechanism in treating inflammatory diseases.Methods:The Untargeted Metabolomics was used to identify the total components of secondary metabolites in Hei-Yun-Xiang.The Hei-Yun-Xiang's active components were screened by the oral bioavailability>30%and drug-likeness>0.10 from the total component of Hei-Yun-Xiang.The TCMSP and standard chemical databases screened the main active components.The Swiss target prediction and the UniProt database predicted the potential targets of Hei-Yun-Xiang's active components.To obtain the potential targets of Hei-Yun-Xiang in the treatment of inflammatory diseases,we compare the above targets with OMIM,NCBI,and GENECARD.Combined with string analysis of Hei-Yun-Xiang's target protein interaction,the R4.0.3 software was used to enrich and analyze Hei-Yun-Xiang's potential targets'GO annotation and KEGG pathway.The"Mongolian medicine-active component-core target-pathway"network structure diagram of Hei-Yun-Xiang in anti-inflammatory effect was constructed using Cytoscape 3.8.0 software.AutoDock Vina 1.1.2 molecular docking software was used to target proteins and the active components interaction model.Results:22 highly active compounds were screened from Hei-Yun-Xiang,of which 19 were related to inflammation.324 targets related to inflammation were predicted and analyzed;targets were mainly composed of genes such as inflammatory biological processes induced by bacterial molecules such as lipopolysaccharide,cell membrane function,and serine/threonine kinase activation.Targets were enriched into the 179 KEGG-related pathways.Pathways mainly include lipid metabolism,arteriosclerosis,neuroactive receptor-ligand binding pathway,PI3K Akt signaling pathway.Molecular docking demonstrated that astrapterocarpan,chimonanthine,columbianetin_acetate,tretinoin,tussilagone,columbianetin_acetate,n-Feruloyltyramine had good binding to eight key proteins,and AKT1 and HSP90AA1 was the target protein with the best binding activity,suggesting that AKT1 and HSP90AA1 could be the essential mediator responsible for signaling transduction after Hei-Yun-Xiang administration.Conclusion:Hei-Yun-Xiang can inhibit the inflammatory reaction by its multi-component,multi-target,and multi-channel treatment of inflammatory disease,interfering with the inflammatory reaction induced by bacterial molecules such as lipopolysaccharide or by intervening in lipid and inflammation-related arteriosclerosis-related pathways.展开更多
基金The Inner Mongolia Autonomous Region Personalized Medicine Engineering Technology Research Center Open Foundation(MDK2021056,MDK2019083,MDK2019085)The Central Government Guiding Special Funds for Development of Local Science and Technology(2020ZY0020)。
文摘Objective:To identify the secondary metabolites of Hei-Yun-Xiang(黑云香),predict its target by network pharmacology,and the target binding activity was demonstrated by molecular docking to explore its mechanism in treating inflammatory diseases.Methods:The Untargeted Metabolomics was used to identify the total components of secondary metabolites in Hei-Yun-Xiang.The Hei-Yun-Xiang's active components were screened by the oral bioavailability>30%and drug-likeness>0.10 from the total component of Hei-Yun-Xiang.The TCMSP and standard chemical databases screened the main active components.The Swiss target prediction and the UniProt database predicted the potential targets of Hei-Yun-Xiang's active components.To obtain the potential targets of Hei-Yun-Xiang in the treatment of inflammatory diseases,we compare the above targets with OMIM,NCBI,and GENECARD.Combined with string analysis of Hei-Yun-Xiang's target protein interaction,the R4.0.3 software was used to enrich and analyze Hei-Yun-Xiang's potential targets'GO annotation and KEGG pathway.The"Mongolian medicine-active component-core target-pathway"network structure diagram of Hei-Yun-Xiang in anti-inflammatory effect was constructed using Cytoscape 3.8.0 software.AutoDock Vina 1.1.2 molecular docking software was used to target proteins and the active components interaction model.Results:22 highly active compounds were screened from Hei-Yun-Xiang,of which 19 were related to inflammation.324 targets related to inflammation were predicted and analyzed;targets were mainly composed of genes such as inflammatory biological processes induced by bacterial molecules such as lipopolysaccharide,cell membrane function,and serine/threonine kinase activation.Targets were enriched into the 179 KEGG-related pathways.Pathways mainly include lipid metabolism,arteriosclerosis,neuroactive receptor-ligand binding pathway,PI3K Akt signaling pathway.Molecular docking demonstrated that astrapterocarpan,chimonanthine,columbianetin_acetate,tretinoin,tussilagone,columbianetin_acetate,n-Feruloyltyramine had good binding to eight key proteins,and AKT1 and HSP90AA1 was the target protein with the best binding activity,suggesting that AKT1 and HSP90AA1 could be the essential mediator responsible for signaling transduction after Hei-Yun-Xiang administration.Conclusion:Hei-Yun-Xiang can inhibit the inflammatory reaction by its multi-component,multi-target,and multi-channel treatment of inflammatory disease,interfering with the inflammatory reaction induced by bacterial molecules such as lipopolysaccharide or by intervening in lipid and inflammation-related arteriosclerosis-related pathways.
