Tripterygium Glycosides in the Treatment of Asthma: Integrating Network Pharmacology, Molecular Docking and In Vitro Preliminary Pharmacological Evaluation

Abstract

Objectives The mechanism of tripterygium glycosides (TG) in the treatment of asthma was explored by utilizing network pharmacology, molecular docking, and in vitro preliminary pharmacological tests. Methods An 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. Results There 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. Conclusion TG 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.