AUTHOR=Zhang Mengyuan , Lin Jiangtao , Zhang Jingyuan , Zhao Ruiheng , Wan Jingxuan , Nong Ying 

TITLE=Artesunate inhibits airway remodeling in asthma via the MAPK signaling pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1145188

DOI=10.3389/fphar.2023.1145188

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Artesunate (ART), is a semi-synthetic water-soluble artemisinin derivative extracted from the plant <italic>Artemisia annua</italic>, which is often used to treating malaria. <italic>In vivo</italic> and <italic>in vitro</italic> studies suggested it may help decrease inflammation and attenuate airway remodeling in asthma. However, its underlying mechanism of action is not elucidated yet. Herein, an attempt is made to investigate the ART molecular mechanism in treating asthma.</p><p><bold>Methods:</bold> The BALB/c female mice sensitized <italic>via</italic> ovalbumin (OVA) have been utilized to establish the asthma model, followed by carrying out ART interventions. Lung inflammation scores by Haematoxylin and Eosin (H&amp;E), goblet cell hyperplasia grade by Periodic Acid-Schiff (PAS), and collagen fibers deposition by Masson trichrome staining have been utilized for evaluating how ART affected asthma. RNA-sequencing (RNA-seq) analyses were performed to identify differentially expressed genes (DEGs). The DEGs were analyzed by Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Protein-Protein interaction (PPI) function analyses. Hub clusters were found by Cytoscape MCODE. Subsequently, Real-Time quantitative PCR (RT-qPCR) verified the mRNA expression profiles of DEGs. Finally, immunohistochemistry (IHC) and western blots have validated the relevant genes and potential pathways.</p><p><bold>Results:</bold> ART considerably attenuated inflammatory cell infiltration, mucus secretion, and collagen fibers deposition. KEGG pathway analysis revealed that the ART played a protective role <italic>via</italic> various pathways including the mitogen-activated protein kinase (MAPK) pathway as one of them. Moreover, ART could alleviate the overexpression of found in inflammatory zone 1(FIZZ1) as revealed by IHC and Western blot analyses. ART attenuated OVA-induced asthma by downregulating phosphorylated p38 MAPK.</p><p><bold>Conclusion:</bold> ART exerted a protective function in a multitarget and multi-pathway on asthma. FIZZ1 was a possible target for asthma airway remodeling. The MARK pathway was one of the key pathways by which ART protected against asthma.</p>