Tougu Xiaotong Capsules for treating arthritis according to the principle of “Same Treatment for Different diseases”: analysis based on integrated pharmacology, molecular docking techniques and molecular dynamics simulation

doi:10.12307/2025.729

Abstract

Abstract: BACKGROUND: Our previous research found that Tougu Xiaotong Capsules can be used not only for the treatment of osteoarthritis, but also for rheumatoid arthritis and gouty arthritis. However, the specific mechanism of action of “Same Treatment for Different Diseases” is still unclear.
OBJECTIVE: To identify the main effects and mechanisms of Tougu Xiaotong Capsules in the treatment of osteoarthritis, rheumatoid arthritis and gouty arthritis with the treating principle of “Same Treatment for Different Diseases” by the methodologies of integrated pharmacology, molecular docking techniques and molecular dynamics simulation.
METHODS: The active chemical components of Tougu Xiaotong Capsules and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Swiss Target Prediction database. The disease genes for osteoarthritis, rheumatoid arthritis and gouty arthritis were obtained from the GeneCards and OMIM databases. Cytoscape 3.7.2 software was used to construct a drug-component-disease-target network diagram and a protein-protein interaction network. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted using the Daivd database. Molecular docking simulations were performed on the CB-DOCK2 website, and molecular dynamics simulations were carried out using the GROMACS 2020.6 software.
RESULTS AND CONCLUSION: (1) A total of 50 active components of Tougu Xiaotong Capsules were screened, with 184 potential targets and 29 intersection targets across the three types of arthritis. (2) The gene ontology enrichment analysis of the intersection targets indicated that the key gene functions of Tougu Xiaotong Capsules in treating the three types of arthritis were found to be cellular response to lipopolysaccharide, inflammatory response, extracellular matrix, protein binding, and zinc ion binding. (3) Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified key pathways as interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, NOD-like receptor and Toll-like receptor signaling pathways. (4) Six core targets [interleukin-6, interleukin-1β, prostaglandin endoperoxide synthase 1, prostaglandin endoperoxide synthase 2, cytochrome P450 1A2 (CYP1A2) and C-X-C chemokine ligand 8] were determined based on the protein-protein interaction network. (5) Molecular docking results confirmed that (+)-catechin, β-sitosterol, kaempferol, myricetin, and wallichilide had good structure-activity relationships. Molecular dynamics simulations further confirmed the stable binding of CYP1A2 with wallichilide, corroborating the network pharmacology and molecular docking results. Therefore, Tougu Xiaotong Capsules may regulate the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, and other signaling pathways by targeting interleukin-1β, prostaglandin endoperoxide synthase 1, prostaglandin endoperoxide synthase 2 and CYP1A2, exert an effect of “Same Treatment for Different Diseases” on osteoarthritis, rheumatoid arthritis and gouty arthritis.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Tougu Xiaotong Capsules, same treatment for different diseases, osteoarthritis, rheumatoid arthritis, gouty arthritis, integrated pharmacology, molecular docking technology, molecular dynamics simulation, engineered tissue construction

CLC Number:

Lin Yixin, Wang Wenyi, Lei Xiaoqing, Ma Dezun, Huang Yanfeng, Fu Changlong, Ye Jinxia. Tougu Xiaotong Capsules for treating arthritis according to the principle of “Same Treatment for Different diseases”: analysis based on integrated pharmacology, molecular docking techniques and molecular dynamics simulation[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(24): 5093-5101.

Figures/Tables 13

2.2 疾病相关靶点与药物-疾病交集靶点经过GeneCards和OMIM数据库检索，获得骨关节炎、类风湿性关节炎及痛风性关节炎靶点分别为716，320，1 489个，交集靶点共有109个。疾病交集靶点与药物靶点交集共获得“异病同治”靶点29个，如图1所示。 2.3 蛋白相互作用网络通过将骨关节炎、类风湿性关节炎及痛风性关节炎的潜在靶点基因导入到STRING数据库，构建疾病与成分靶点的蛋白质-蛋白质互作网络，如图2所示。该网络包含了109个相互关联的蛋白质，筛选得到核心靶点白细胞介素6、白细胞介素1β、前列腺素内过氧化物合酶(prostaglandin-endoperoxide synthase，PTGS)1、前列腺素内过氧化物合酶2、CYP1A2、CXCL8，可能是透骨消痛胶囊治疗骨关节炎、类风湿性关节炎及痛风性关节炎的重要PPI网络。 2.4 潜在靶点GO及KEGG通路富集分析 GO富集分析结果显示，透骨消痛胶囊异病同治骨关节炎、类风湿性关节炎及痛风性关节炎靶点涉及的生物过程主要包括细胞对脂多糖的反应、炎症反应、RNA聚合酶Ⅱ启动子转录的正调控、基因表达的正调控、转录的正调控、DNA模板信号转导等；涉及的细胞组分主要包括细胞外空间、富含ficolin-1的颗粒管腔、细胞外基质等；涉及的分子功能主要包括蛋白质结合、锌离子结合、血红素结合、铁离子结合、酶结合、RNA聚合酶Ⅱ转录因子活性，配体激活的序列特异性DNA结合等，结果如图3所示。 KEGG通路富集分析结果显示，透骨消痛胶囊治疗骨关节炎、类风湿性关节炎及痛风性关节炎的主要通路为白细胞介素17信号通路、肿瘤坏死因子信号通路及NOD样受体、Toll样受体信号通路等，结果如图4所示。并绘制核心信号通路与核心靶点的桑基图，将通路与靶点之间的相关性可视化，结果如图5所示。 2.5 分子对接结果选取核心靶点白细胞介素6、白细胞介素1β、前列腺素内过氧化物合酶1、前列腺素内过氧化物合酶2、CYP1A2、CXCL8与beta-sitosterol、kaempferol、myricanone、quercetin、wallichilide等成分进行分子对接，结果如表2所示。分子对接结果显示，CYP1A2与wallichilide(川芎内酯)、kaempferol(山奈酚)、quercetin(槲皮素)结合效果最好，前列腺素内过氧化物合酶2与其余化合物结合皆有较好的效果，关键化合物与核心靶蛋白分子之间的对接模式如图6所示。"

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