Zhang Mengyuan, Lin Jiangtao, Zhang Jingyuan, Zhao Ruiheng, Wan Jingxuan, Nong Ying
Department of Respiratory and Critical Care, China-Japan Friendship Hospital, Beijing, China.
Graduate School of Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China.
Front Pharmacol. 2023 Mar 14;14:1145188. doi: 10.3389/fphar.2023.1145188. eCollection 2023.
Artesunate (ART), is a semi-synthetic water-soluble artemisinin derivative extracted from the plant , which is often used to treating malaria. and 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. The BALB/c female mice sensitized ovalbumin (OVA) have been utilized to establish the asthma model, followed by carrying out ART interventions. Lung inflammation scores by Haematoxylin and Eosin (H&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. ART considerably attenuated inflammatory cell infiltration, mucus secretion, and collagen fibers deposition. KEGG pathway analysis revealed that the ART played a protective role 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. 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.
青蒿琥酯（ART）是一种从植物中提取的半合成水溶性青蒿素衍生物，常用于治疗疟疾。多项研究表明，它可能有助于减轻炎症并减轻哮喘中的气道重塑。然而，其潜在的作用机制尚未阐明。在此，我们试图研究ART治疗哮喘的分子机制。利用对卵清蛋白（OVA）致敏的BALB/c雌性小鼠建立哮喘模型，然后进行ART干预。通过苏木精和伊红（H&E）染色评估肺部炎症评分，通过过碘酸希夫（PAS）染色评估杯状细胞增生程度，通过Masson三色染色评估胶原纤维沉积，以评估ART对哮喘的影响。进行RNA测序（RNA-seq）分析以鉴定差异表达基因（DEG）。通过基因本体论（GO）术语、京都基因与基因组百科全书（KEGG）通路和蛋白质-蛋白质相互作用（PPI）功能分析对DEG进行分析。通过Cytoscape MCODE找到枢纽簇。随后，实时定量PCR（RT-qPCR）验证了DEG的mRNA表达谱。最后，免疫组织化学（IHC）和western印迹验证了相关基因和潜在通路。ART显著减轻了炎症细胞浸润、黏液分泌和胶原纤维沉积。KEGG通路分析表明，ART在多种通路中发挥保护作用，其中包括丝裂原活化蛋白激酶（MAPK）通路。此外，免疫组织化学和western印迹分析显示，ART可减轻炎症区1（FIZZ1）中发现的过表达。ART通过下调磷酸化的p38 MAPK减轻OVA诱导的哮喘。ART在哮喘中发挥多靶点、多通路的保护作用。FIZZ1可能是哮喘气道重塑的一个靶点。MARK通路是ART预防哮喘的关键通路之一。
