Department of Dermatology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Hainan, China.
Medical Cosmetology Clinic, Hainan Yilimei Medical Cosmetology Co., Hainan, China.
Medicine (Baltimore). 2023 Oct 20;102(42):e34512. doi: 10.1097/MD.0000000000034512.
Tripterygium wilfordii hook (TWH) has been used to treat Behcet's disease (BD) but its underlying mechanism remains unclear. This study aims to explore the mechanism of TWH on BD using network pharmacology and molecular docking. The bioactive constituents of TWH and their corresponding target genes were extracted from the Traditional Chinese Medicine systems pharmacology database and analysis platform. BD target genes were obtained by searching the DisGeNet and GeneCards databases. Gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were conducted to elucidate the function of overlapping genes between TWH and BD target genes. A protein-protein interaction network was constructed using Cytoscape and STRING platforms, and the core target genes were identified from the overlapping genes. Finally, molecular docking was used to assess the binding affinity between the core targets and TWH bioactive constituents. We identified 25 intersection genes related to both TWH and BD and 27 bioactive ingredients of TWH. Through analysis of protein-protein interaction network, 6 core targets (TNF, IFNG, prostaglandin-endoperoxide synthase 2, NOS2, VCAM-1, and interleukin-2) were screened out. Enrichment analysis demonstrated that the antioxidant properties of TWH constituents might play a significant role in their therapeutic effects. Molecular docking revealed high binding affinity between the bioactive constituents of TWH, such as kaempferol, triptolide, 5, 8-Dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3)-coumarin, and their corresponding target genes, suggesting the potential of TWH to treat BD. Our investigation clarified the active components, therapeutic targets of BD in the treatment of TWH and provided a theoretical foundation for further researches.
雷公藤（TWH）已被用于治疗白塞病（BD），但其潜在机制尚不清楚。本研究旨在采用网络药理学和分子对接技术探讨 TWH 治疗 BD 的机制。从中药系统药理学数据库和分析平台中提取 TWH 的生物活性成分及其相应的靶基因。通过搜索 DisGeNet 和 GeneCards 数据库获得 BD 靶基因。对 TWH 与 BD 靶基因重叠基因进行基因本体注释和京都基因与基因组百科全书通路富集分析，阐明重叠基因的功能。使用 Cytoscape 和 STRING 平台构建蛋白质-蛋白质相互作用网络，并从重叠基因中识别核心靶基因。最后，采用分子对接评估核心靶基因与 TWH 生物活性成分之间的结合亲和力。我们确定了 25 个与 TWH 和 BD 相关的交集基因和 27 个 TWH 的生物活性成分。通过蛋白质-蛋白质相互作用网络分析，筛选出 6 个核心靶标（TNF、IFNG、前列腺素内过氧化物合酶 2、NOS2、VCAM-1 和白细胞介素-2）。富集分析表明，TWH 成分的抗氧化特性可能在其治疗作用中发挥重要作用。分子对接表明 TWH 的生物活性成分（如山奈酚、雷公藤内酯醇、5,8-二羟基-7-(4-羟基-5-甲基香豆素-3)-香豆素）与其相应的靶基因之间具有高结合亲和力，提示 TWH 可能对白塞病具有治疗作用。我们的研究阐明了 TWH 治疗 BD 的活性成分和治疗靶点，为进一步研究提供了理论基础。
