基于网络药理学和分子对接分析草乌致肝毒性的机制OA

Objective To explore the mechanism of hepatotoxicity induced by Aconitum kusnezoffii using network pharmacology and molecular docking technology.Methods Toxic components of Aconitum kusnezoffii were screened via the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),PubChem,Swiss ADME,and literature review.Potential targets of these components were predicted using the Swiss Target Prediction database.Hepatotoxicity-related targets were retrieved from the GeneCards database,and overlapping targets were subjected to gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway analyses.Networks including toxic component-target,toxic component-hepatotoxicity overlapping targets,toxic component-overlapping targets-core pathways and protein-protein interaction(PPI)were constructed using Cytoscape.Molecular docking was performed with AutoDock,and visualization was conducted using PyMol.Results Eight hepatotoxic components were identified:izoteoline,karakoline,3-deoxyaconitine,3-acetylaconitine,crassicauline A,yunaconitine,napelline,and hypaconitine.Twenty-four overlapping targets associated with hepatotoxicity were identified.GO and KEGG analyses revealed that Aconitum kusnezoffii induces hepatotoxicity through processes such as the estrogen signaling pathway,PI3K-Akt signaling pathway,response to exogenous stimuli,and regulation of blood circulation.Molecular docking demonstrated strong binding affinities between the eight toxic components and key hepatotoxicity targets(HSP90AA1,EGFR,MTOR,MMP9,ABCB1).Conclusion This study preliminarily elucidates the toxic components,mechanisms,targets,and pathways underlying Aconitum kusnezoffii-induced hepatotoxicity using network pharmacology and molecular docking,providing a foundation for further research on its clinical applications and mechanistic evaluations.