Jingfang granule alleviates Pseudomonas aeruginosa-induced acute lung inflammation through suppression of STAT3/IL-17/NF-κB pathway based on network pharmacology analysis and experimental validation.
Jingfang granule alleviates Pseudomonas aeruginosa-induced acute lung inflammation through suppression of STAT3/IL-17/NF-κB pathway based on network pharmacology analysis and experimental validation.
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基于网络药理学分析和实验验证，经方颗粒通过抑制STAT 3/IL-17/NF-κB通路抑制铜绿假单胞菌诱导的急性肺炎症。
DOI：
10.1016/j.jep.2023.116899
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发表时间：
2023-07
影响因子：
5.4
通讯作者：
Mengdi Gu;Wen-Hao Su;Jiangqin Dai;Jue Wang;Xiaolei Jia;Jingchun Yao;Guimin Zhang;Qingjun Zhu;Z. Pang
中科院分区：
文献类型：
--
作者：
Mengdi Gu;Wen-Hao Su;Jiangqin Dai;Jue Wang;Xiaolei Jia;Jingchun Yao;Guimin Zhang;Qingjun Zhu;Z. Pang
Ethnopharmacological relevancePseudomonas aeruginosa is an opportunistic bacterial pathogen which is the second leading cause of hospital-acquired pneumonia. Jingfang granule (JFG) is an herbal formula of Traditional Chinese medicine (TCM) widely used in treatment of acute respiratory tract infections in China. However, the molecular mechanisms of JFG in treatment ofP. aeruginosa-induced acute pneumonia are not clear.Aim of studyThis study aimed to investigate the mechanisms underlying the effects of JFG onP. aeruginosa-induced acute inflammation using a mouse model of bacterial acute pneumonia.Materials and methodsThe chemical components and targets of JFG were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and theP. aeruginosapneumonia-related targets were obtained from the disease databases, including Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNet. The protein-protein interaction (PPI) network was constructed using STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Molecular docking was performed using AutoDockTools 1.5.6. Furtherin vivoexperiments employed a mouse model ofP. aeruginosaacute pneumonia to verify the target proteins and signaling pathways affected by JFG, which were predicted by the network pharmacology analysis.ResultsA total of 218 active components and 257 targets of JFG were retrieved from TCMSP database. Moreover, 99 intersectant targets were obtained between the 257 JFG targets and 694 disease targets. Among the intersectant targets, STAT3, IL-6, AKT1, TNF, MAPK1, MAPK3 and EGFR were identified to be the key therapeutic targets through PPI network analysis, and STAT3 was in the center of the network, which is a key regulator of IL-17 expression. KEGG pathway enrichment analysis suggested that IL-17 signaling pathway was one of the crucial inflammatory pathways affected by JFG in treatment ofP. aeruginosapneumonia. Furthermore, thein vivoexperiments demonstrated that the JFG-treated mice displayed reduced proinflammatory cytokine production (IL-17, IL-1β, IL-6 and TNF), diminished neutrophil infiltration and decreased mortality, compared with the non-drug-treated mice duringP. aeruginosalung infection. Moreover, the expression or phosphorylation levels of the key regulators in STAT3/IL-17/NF-κB axis including STAT3, ERK1/2 (MAPK3/1), AKT, NF-κB p65 and RORγt were significantly reduced in the lung tissues of the JFG-treated mice.ConclusionJFG was effective in treatment ofP. aeruginosaacute lung infection, which reduced inflammatory responses through suppressing STAT3/IL-17/NF-κB pathway.
