Network pharmacology combining molecular docking to unveil the anti-inflammatory mechanism of Aconitum Heterophyllum

Abstract Objective The objective of this study was to examine the impact and underlying mechanisms of Aconitum Heterophyllum in mitigating cellular inflammation. Methods Initially, the principal components of A.heterophyllum were obtained from relevant literature sources, and the corresponding protein targets of A.heterophyllum were searched on Pubchem and Swiss Target Prediction database. Subsequently, the genes linked with inflammation were gathered from PHARMGKB, OMIM, and GeneCards databases. The core targets were screened, and a protein–protein interaction (PPI) network was constructed using Cytoscape 3.9.1. For general targets, the gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. Molecular docking was further applied for the core targets and compounds. Finally, the RAW264.7 cellular inflammation model was constructed, and MTT assay, Griess assay and qRT-PCR assay were used to initially validate the anti-inflammatory effects of A. heterophyllum and its underlying mechanisms. Results In total, 35 compounds and 1322 targets were associated with A.heterophyllum , along with 3534 genes implicated in inflammation. The intersection analysis yielded 244 common targets, contributing to the enrichment of 146 pathways. Notably, results of molecular docking revealed strong binding between the active compounds and core targets. Furthermore, in vitro experiments indicated the anti-inflammatory potential of A.heterophyllum ’s active ingredient through the modulation of the EGFR/JAK2/STAT3 pathway and EGFR-AKT pathway, as well as inhibiting cellular NO release to reduce the inflammatory response. Conclusion A.heterophyllum exerts anti-inflammatory activity by inhibiting EGFR-AKT1 activity and inhibiting EGFR/JAK2/STAT3 signal transduction.