ObjectivesThe mechanism of tripterygium glycosides (TG) in the treatment of asthma was explored by utilizing network pharmacology, molecular docking, and in vitro preliminary pharmacological tests.MethodsAn analysis of the bioactive ingredients of TG was conducted using the Traditional Chinese Medicine Systems Pharmacology Database database or predicted by FAFdrugs4, with relevant targets gathered from HERB, Swiss Target Prediction, STITCH, and SEA databases, and the targets for asthma were collected in Drugbank, DisGeNET, and GeneCards databases. Compound-target-pathway interactions and the function of putative targets were annotated by Cytoscape 3.6.0 and Database Visualization and Integrated Discovery, respectively. The affinity of the key ingredient and hub targets was assessed by molecular docking using AutoDock Vina software. Real-time quantitative polymerase chain reaction, cell-secreted cytokine assay, and ELISA were used to explore the effect of TG and its key ingredient triptolide (TP) for asthma.ResultsThere were 12 bioactive ingredients in TG with 335 corresponding targets, 2672 asthma-associated targets, and 204 TG anti-asthma targets. TP and Tripterine were identified as the two key ingredients. RELA and TP53 exhibited the best topological index in protein-protein interaction network analysis and were regarded as hub targets. TG might play a role in biological processes such as lipopolysaccharide-mediated signaling pathway, regulation of nitric oxide biosynthetic process and mainly related to toll-like receptor, TNF and apoptosis signaling pathways. Molecular docking revealed that TP effectively bound to hub targets. In vitro experiments demonstrated that TG and TP reversed the RNA expression of airway remodeling marker CDH1 and FN. Moreover, TP reduced the secretion of vascular endothelial growth factor, implicating its role in airway remodeling.ConclusionTG might act on target genes RELA and TP53, utilizing the active ingredient TP, to regulate signaling pathways such as toll-like receptor, TNF, and apoptosis, thereby playing a role in the improving airway remodeling in asthma.

中文翻译：

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雷公藤多甙治疗哮喘：整合网络药理学、分子对接和体外初步药理评价

目的 利用网络药理学、分子对接和体外初步药理试验等手段，探讨雷公藤多甙（TG）治疗哮喘的作用机制。 FAFdrugs4 预测，相关靶标收集自 HERB、Swiss Target Prediction、STITCH 和 SEA 数据库，哮喘靶标收集于 Drugbank、DisGeNET 和 GeneCards 数据库。化合物-靶标-通路相互作用和推定靶标的功能分别通过 Cytoscape 3.6.0 和数据库可视化和集成发现进行注释。使用 AutoDock Vina 软件通过分子对接评估关键成分和中心靶标的亲和力。采用实时定量聚合酶链反应、细胞分泌细胞因子测定和ELISA等方法探讨TG及其关键成分雷公藤内酯醇（TP）的治疗哮喘作用。结果TG中有12种生物活性成分，335个相应靶点，2672个哮喘患者。相关目标，以及 204 个 TG 抗哮喘目标。TP和雷公藤红素被确定为两种关键成分。RELA和TP53在蛋白质-蛋白质相互作用网络分析中表现出最好的拓扑指数，被视为枢纽目标。TG可能在脂多糖介导的信号通路、一氧化氮生物合成过程的调节等生物过程中发挥作用，主要与Toll样受体、TNF和细胞凋亡信号通路有关。分子对接显示 TP 有效地结合到枢纽目标上。体外实验表明，TG 和 TP 逆转气道重塑标志物 CDH1 和 FN 的 RNA 表达。此外，TP还能减少血管内皮生长因子的分泌，提示其在气道重塑中的作用。结论TG可能作用于靶基因RELA和TP53，利用活性成分TP调节Toll样受体、TNF、细胞凋亡等信号通路。 ，从而在改善哮喘气道重塑中发挥作用。