The Potential Mechanism of Andrographis Paniculata in Improving Myocardial Ischemia/Reperfusion Injury Based on Network Pharmacology and Molecular Docking
ZHAO Weikun
XU Tongtong
LYU Xiangwei
CHEN Liqin
XU Zihao
MO Wenyue
LU Yufen
LI Yuechang
Abstract：Objective:The potential targets and mechanisms of andrographis paniculata in improving myocardial ischemia/reperfusion injury(MIRI)were explored by network pharmacology and molecular linkage techniques.Methods:The active ingredients and target sites of andrographis paniculata were screened out using the Pharmacology Database and Analysis Platform for Traditional Chinese Medicine System(TCMSP).The target genes were annotated using the UniPort database.The targets of MIRI were obtained by the Human Gene Database(GeneCards),DisGeNET,Therapeutic Target Database(TTD),and the Online Human Mendelian Genetic Database(OMIM).The common target genes of andrographis paniculata and MIRI were obtained by the Venn online software and presented as Venn plots.The visualization network diagram of"drug-drug active ingredient-target"was constructed by using Cytoscape 3.9.1 software.The Annotation,Visualization and Comprehensive Discovery Database(DAVID)was applied to conduct gene ontology(GO)classification enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the intersection targets.Protein interaction(PPI)analysis of the intersection targets was conducted through the STRING database,and the PPI network was analyzed using the Cytohubba plugin of Cytoscape 3.9.1 software to obtain the key targets.The molecular docking verification of the screened six key target protein receptors and drug active distributors was conducted through AutoDock Tools 1.5.7 software and PyMol 2.5.0.Results:Thirty-six effective active components and 172 target genes of andrographis paniculata were screened,including 1 466 MIRI-related target genes and 49 drug and disease intersection targets.The key core targets were obtained including AKT1,TNF,IL6,CASP3,NOS3,and TP53,which were mainly involved in biological processes such as nitric oxide biosynthesis,lipopolysaccharide-mediated signal transduction,apoptosis,gene expression,and inflammatory response.KEGG pathway enrichment analysis revealed that the main mechanisms of action related to lipids and atherosclerosis,the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathway,the advanced glycation end product(AGE)-advanced glycation end product receptor(RAGE)signaling pathway in diabetic complications,Epstein-Barr virus infection,and interleukin(IL)-17 signaling pathway,etc.Conclusion:The intervention effect of andrographis paniculata on MIRI shows the regulatory characteristics of multiple components,multiple targets,multiple pathways and multiple links.Its regulatory targets mainly involves AKT1,TNF,IL6,CASP3,NOS3,and TP53,etc.Its regulates pathways may involves oxidative stress and inflammation-related signaling pathways,cell survival and apoptosis-related signaling pathways,etc.This will provide foundation for the subsequent in-depth exploration of the potential molecular mechanism related andrographis paniculata improving MIRI.
Keywords：myocardial ischemia/reperfusion injuryandrographis paniculatanetwork pharmacologymacromolecular dockingmechanism
Publication Date：2025-07-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：16( 1934-1949 )