Study on molecular mechanism of Salviae Miltiorrhizae Radix Et Rhizoma in treatment of chronic pain based on QSAR machine learning model combined with"prolonged illness leading to stasis"theory
Objective:To predict the active components of Salviae Miltiorrhizae Radix Et Rhizoma in the treatment of chronic pain using quantitative structure-activity relationship(QSAR)machine learning model and molecular docking technology,and to explore the molecular mechanism of Salviae Miltiorrhizae Radix Et Rhizoma in the treatment of chronic pain combined with the theory of"prolonged illness leading to stasis"and network pharmacology.Methods:First,the chemical components of Salviae Miltiorrhizae Radix Et Rhizoma and targets of chronic pain were collected through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and the Human Genome database(GeneCards),and the core targets were screened.And the protein interaction(PPI)network was analyzed by STRING database.Then,the intersection targets were analyzed by Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Finally,the QSAR machine learning model and molecular docking technology were used to screen the active ingredients and core targets of Salviae Miltiorrhizae Radix Et Rhizoma in the treatment of chronic pain.Results:①Fifty-five intersection targets and 55 potential active components of Salviae Miltiorrhizae Radix Et Rhizoma in the treatment of chronic pain were screened.The core targets such as serine/threonine kinase 1(AKT1),epidermal growth factor receptor(EGFR)and interleukin(IL)-6 were found through PPI analysis.②Through the function enrichment analysis,45 cell components,87 molecular functions,1 450 biological processes and 140 signaling pathways were obtained,involving signaling pathways such as phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT),IL-17,hypoxia-inducible factor 1(HIF-1),cyclic adenosine monophosphate(cAMP),and mitogen-activated protein kinases(MAPK)signaling pathway.③Through QSAR model and molecular docking,it was found that salvilenone,epidanshenspiroketallactone,salvianan A,isotanshinone Ⅱ and salvianolic acid C in Salviae Miltiorrhizae Radix Et Rhizoma were the active components for treating chronic pain.Conclusion:The active components of Salviae Miltiorrhizae Radix Et Rhizoma in treating chronic pain are diterpenoids,and its mechanism of action is probably related to the regulation of AKT1-mediated signaling pathways.
chronic painSalviae Miltiorrhizae Radix Et Rhizomaquantitative structure-activity relationship(QSAR)machine learningnetwork pharmacology
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NSTL
万方数据
