Exploration of the molecular mechanism of Chinese medicine Huzhang in the intervention of viral pneumonia based on network pharmacology,molecular docking technology and in vitro experiment
Objective:To explore the possible mechanism of Huzhang in the intervention of viral pneumonia by net-work pharmacology,molecular docking technology and in vitro experiment.Methods:The active ingredients and their tar-gets of action of Chinese medicine Huzhang were screened by TCMSP platform,and the related targets of viral pneumonia were screened from GeneCards database.Then the potential targets were obtained by intersection.By using STRING data-base combined with Cytoscape 3.7.2 software,protein-protein interaction(PPI)analysis of intersection targets and topologi-cal analysis were performed on potential targets,and the core components of Huzhang and key targets of viral pneumonia were obtained.GO function analysis and KEGG pathway enrichment analysis were performed on intersection targets by using DAVID database.The"Huzhang-active ingredient-target-pathway"regulatory network was constructed by combining Cyto-scape 3.7.2 software.AutoDock Vina,OpenBabel,PyMOL and other software were used to perform molecular docking be-tween the active components of Huzhang and the key targets of viral pneumonia.Acute lung injury model was established by lipopolysaccharide(LPS)-induced acute lung injury in human typeⅡ alveolar epithelial cell A549,and the results of net-work pharmacology were verified.Results:A total of 10 active ingredients of Huzhang were obtained,corresponding to 188 targets of action and 1216 targets of viral pneumonia,and 93 intersection targets of drugs and diseases were taken.Querce-tin,luteolin,physostigmine,β-sitosterol might be the core components of Huzhang.Serine/threonine kinase 1(Akt1),vascular endothelial growth factor A(VEGFA),tumor necrosis factor(TNF),interleukin-6(IL6),interleukin-1β(IL1β),JUN kinase(JUN),prostaglandin G/H synthetase 2(PTGS2),matrix metalloproteinase-9(MMP-9)and a cysteine prote-ase-3(CASP3)might be the core targets of Huzhang in the intervention of viral pneumonia.GO functional analysis and KEGG pathway enrichment analysis showed that the target proteins played a role by regulating cytokines,growth factors,proteins,protein kinases,TNF,PI3K-Akt,Toll-like receptors and other signaling pathways in extracellular matrix,mito-chondria,nucleoplasm,and cytoplasm.Molecular docking showed that the five core components of Huzhang had strong binding ability with TNF,Akt1,CASP3,IL1β,JUN,TP53 and VEGFA with binding energy<-7.0 kcal/mol,and had good binding ability with IL6 and PTGS2 with binding energy<-5.0 kcal/mol,and had a certain binding ability with MMP-9 with binding energy<-4.25 kcal/mol.The results of in vitro experiments showed that Huzhang could reduce the expres-sions of TNF-α,IL-1β and IL-6 in the model group,with the statistical difference(P<0.01,P<0.05),and could inhibit the expressions of Toll-like receptor 4(TLR4)and nuclear factor-κB(NF-κB),with the statistical difference(P<0.05).Conclusion:Huzhang may play a therapeutic role in the intervention of viral pneumonia by regulating targets such as TNF-α,IL-1β,IL-6,TLR4 and NF-κB.
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