Investigation of the mechanism of action of chemical constituents of celery seed against gout disease using network pharmacology, molecular docking, and molecular dynamics simulations

AbstractAbstractCelery (Apium graveolens L.) has long been considered as a potential herbal medicine for the prevention and treatment of gout. However, the relationship between the chemical constituents and pharmacological activities of this medicinal plant has not been fully investigated yet. Therefore, this study aims to apply network pharmacology, molecular docking and molecular dynamics to explore the relationship between the chemical constituents of celery seed and its biological effects in the treatment of gout. Network pharmacology was built and analyzed based on the data collected from GeneCards, OMIM databases and SwissTargetPrediction web server using Cytoscape 3.9.0 software. The GO and KEGG pathway analysis of the potential targets of celery seed related to gout disease was performed using the ShinyGO v0.75 app. Molecular docking and molecular dynamics were carried out using Autodock vina and NAMD 2.14 software, respectively. The network analysis identified 16 active compounds and thirteen key targets of celery seed in the treatment of gout. The GO analysis and the KEGG pathway enrichment analysis suggested that the mechanism of action of the chemical constituents of celery seed might be involved in several pathways, notably the PI3K-Akt signaling pathway, Ras signaling pathway, and HIF-1 signaling pathway, respectively. Molecular docking and molecular dynamics revealed that apiumetin might be an important chemical that plays a key role in the pharmacological effect of celery seed. These results might be useful to select the Q-markers to control the quality of the products from celery seeds.Communicated by Ramaswamy H. SarmaKeywords: Celery seedgoutnetwork pharmacologymolecular dockingmolecular dynamics Disclosure statementThe authors declare that they have no known competing fnancial interests or personal relationships that could have appeared to influence the work reported in this paper.Data availability statementThe data that support the findings of this study are available from the corresponding author on special request.Additional informationFundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.