文献类型： 外文期刊

第一作者： Han, Xianlei

作者： Han, Xianlei;Zhang, Yue;Zhang, Fan;Wang, Nan;Li, Xiumei;Meng, Yanli;Huo, Jinhai;Wang, Weiming;Chen, Mian;Liu, Fei

作者机构：

关键词： Platycodonis radix; Acute lung injury; Network pharmacology; Molecular docking; PM2.5

期刊名称：JOURNAL OF ETHNOPHARMACOLOGY （ 影响因子：5.4； 五年影响因子：5.4 ）

ISSN： 0378-8741

年卷期： 2025 年 337 卷

页码：

收录情况： SCI

摘要： Ethnopharmacological relevance: Platycodonis radix (PR), the root of Platycodon grandiflorus (Jacq.) A. DC., is a traditional Chinese medicine recognized for its dual role as both a medicinal and dietary substance, exhibiting significant anti-inflammatory properties. It is frequently utilized in the treatment of lung diseases. However, the molecular mechanisms by which PR exerts its effects in the treatment of acute lung injury (ALI) remain unclear. Aim of the study: This study presents a novel strategy that integrates network pharmacology, molecular docking, untargeted metabolomics analysis and experimental validation to investigate the molecular mechanisms through which PR treats ALI. Materials and method: Initially, the bioactive components of PR, along with its targets and pathways in the treatment of ALI, were identified using network pharmacology. Following this, preliminary validation was conducted through molecular docking. The active ingredients in the aqueous extract of PR were characterized using HPLC-MS. Finally, in vivo and in vitro experiments were performed to further validate the findings from the network pharmacology. Results: A total of 14 bioactive components and 156 effective targets were identified using the TCMSP, DisGeNET, Genecard, OMIM databases and Venny 2.1.0. Protein-protein interaction (PPI) analysis revealed 22 core targets including TP53, AKT1, STAT3 and JUN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these targets primarily participate in the regulation of cellular apoptosis, lung cancer and inflammatory pathways. Molecular docking demonstrated that four bioactive components exhibited strong affinities with their respective docking targets. LC-MS analysis confirmed that the aqueous extract of PR contained 87 components, including two active ingredients identified through network pharmacology and molecular docking. Preliminary validation was conducted in mice with ALI induced by acute PM2.5 exposure, revealing that the aqueous extract of PR reduced inflammatory factor levels in bronchoalveolar lavage fluid, enhanced antioxidant capacity in lung tissue, and decreased lung cell apoptosis in PM2.5-exposed mice. Notably, PR alleviated PM2.5-induced ALI through the STAT3, JUN, and AKT1 signaling pathways. Similarly, the results of in vitro intervention experiments further confirmed that the aqueous extract of PR protected pulmonary epithelial cells against PM2.5 exposure through activating AKT1 sinalling pathway, and inhibiting STAT3 and JUN signalling pathways. Conclusion: This study identifies the active components of PR and elucidates the molecular mechanisms by which PR alleviates ALI, specifically by inhibiting the phosphorylation levels of STAT3 and c-JUN, or by activating the phosphorylation level of AKT1. These results provide a foundational basis for the application of PR in the treatment or prevention of lung injuries induced by particulate matter.

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