Efficacy of artesunate in asthma: based on network pharmacology and molecular docking.

Abstract

Asthma has brought great economicburdens to community. Artesunate has shown certain effects on asthma experimentally, but relevant mechanisms are not clear. This study aims to systemically evaluate the efficacy and safety of artesunate and its metabolite, dihydroartemisinin (DHA), in asthma, based on network pharmacology and molecular docking. All the information before March 1st, 2022 was collected. We evaluated the physicochemistry and Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of artesunate and DHA by SwissADME and ADMETlab, identified targets of artesunate and DHA from SwissTargetPrediction and PharmMapper, and acquired genes participating in asthma from GeneCards and DisGeNET. Overlapping targets and hub genes were identified with Maximal Clique Centrality (MCC) algorithm in Cytoscape, cytoHubba. Enrichment analyses were performed to analyze the potential mechanisms and target sites. Molecular docking was utilized to investigate the receptor-ligand interactions on Autodock Vina and visualized in PyMOL. Artesunate and DHA showed acceptable druglikeness and safety for clinical application. A total of 282 targets of compounds and 7,997 targets of asthma were identified. 172 overlapping targets were visualized in a compound-target and protein-protein interaction network. Biofunction analysis showed the clustering associations with biosynthesis and metabolism of and response to steroid hormone, immune and inflammatory response, airway hyperresponsiveness, airway remodeling and cell survival and death regulation. CCND1, CASP3, MTOR, ERBB2, MAPK3, EGFR, MAP2K1, PTGS2, JAK2, and CASP8 were identified as the hub targets. Molecular docking indicated 10 stable receptor-ligand interactions, except for CASP3. Artesunate has the potential to be a potent and safe anti-asthmatic agent based on diverse therapeutic mechanisms and acceptable safety.