Artemisia annua L. in treatment for Mycobacterium abscessus infection based on network pharmacology, molecular docking and in vitro experiments

Abstract

Objective To explore the mechanism of Artemisia annua L. (A. annua) in treatment of Mycobacterium abscessus (M. abscessus) infection with aid of network pharmacology and molecular docking. Methods The active components of A. annua were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) system, and the targets of A. annua were predicted using PharmMapper and SwissTargetPrediction. Targets related to M. abscessus infection were obtained from GeneCards database and OMIM database. After obtaining the common targets of them, a target protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Then Metascape database was employed to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The main potential active components of A. annua were screened out for molecular docking with the core targets. The extracts of A. annua and the main potential active ingredients screened out were tested in vitro to explore its minimum inhibitory concentration (MIC), its combined efficacy with common anti-M. abscessus antibiotics in vitro, and its effect on the viability of M. abscessus. Results A total of 48 targets of A. annua were found to be involved in the pathogenesis of M. abscessus infection. A total of 6 targets, MMP9, MAPK3, CASP3, IL2, CASP1, and MMP2, were predicted to be the core targets of A. annua in the treatment of this disease. KEGG enrichment analysis showed that A. annua may treat this disease through IL-17 signaling pathway, neutrophil extracellular trap formation, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, MAPK signaling pathway and other inflammatory and immune-related signaling pathways. Molecular docking results indicated that A. annua had a high affinity with these core targets. Tamarixetin, artemetin, dihydroartemisinin and Artemisia annua L. were screened to have antibacterial activity against M. abscessus in vitro, with a MIC value of 200, 100, 100 and 100 μg/mL, respectively. After combined with the exacts of A. annua, the MIC value of clarithromycin, azithromycin, amikacin, imipenem, and cefoxitin was all decreased than that of their single use, with a declining multiple ranging from 2 to 8 times. Conclusion A. annua may act on M. abscessus infection through multiple targets and multiple pathways. It has antibacterial effect in vitro and shows a synergistic effect with some antibiotics against the bacteria.

Keywords

• artemisia annua l.
• mycobacterium abscessus
• network pharmacology
• molecular docking
• minimum inhibitory/bactericidal concentrations