The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, China.
The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, China; Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Ann Palliat Med. 2021 Jul;10(7):7706-7720. doi: 10.21037/apm-21-1691.
Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction and periarticular osteophyte formation. One therapeutic option for this condition, the Wutou Decoction (WTD) Chinese medicine formula, is satisfactory in its efficacy. Here, we used bioinformatic and molecular docking techniques to investigate the mechanism of action of WTD in the treatment of OA.
The active compounds (and their target proteins) of 5 Chinese herbs in WTD were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The action targets of WTD for OA were obtained by searching the Therapeutic Target Database and by mining the microarray data in the Gene Expression Omnibus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to identify key targets for OA treatment with the help of Database for Annotation, Visualization, and Integrated Discovery. Based on the Cytoscape software version 3.6.1, the visual networks of the "TCM drugs-Active Compounds-Targets-Diseases" and protein-protein interaction of the key targets of WTD for the treatment of OA were constructed. The core active compounds and the key targets obtained were molecularly docked and validated.
Analyses revealed 140 active compounds in WTD, 123 of which had a total of 163 corresponding targets. In addition, 331 differentially expressed genes and 227 OA-related targets were obtained. The interaction networks among 32 key targets were identified. The biological processes of WTD in treating OA mainly involved regulation of inflammatory factors, transcription of genetic materials, cell cycle, angiogenesis, and endocrine regulation. The signaling pathways involved mainly included TNF signaling pathway, rheumatoid arthritis signaling pathway, cancer-related signals, vascular endothelial growth factor signaling pathway, and osteoclast differentiation signaling pathways. Molecular docking showed that 7 core compounds including quercetin and kaempferol had strong affinities with key target proteins for the WTD treatment of OA.
WTD with multi-component can treats OA through multi-pathway. Its active compounds, including quercetin and kaempferol, can exert their therapeutic effects on OA by acting on TNF, PTGS2, MMP2, IL-6, IL-1β, and other key targets to regulate inflammation, immunity, autophagy, and endocrine-related signaling pathways.
骨关节炎（OA）是一种慢性关节疾病，其特征为软骨破坏和关节周围骨赘形成。对于这种疾病的一种治疗选择是中药方剂乌头汤（WTD），其疗效令人满意。在这里，我们使用生物信息学和分子对接技术来研究 WTD 治疗 OA 的作用机制。
通过搜索中药系统药理学数据库与分析平台（TCMSP），获得 WTD 中 5 种草药的活性化合物（及其靶蛋白）。通过搜索治疗靶点数据库（TTD）并挖掘基因表达综合数据库（GEO）中的微阵列数据，获得 WTD 治疗 OA 的作用靶点。使用数据库注释、可视化和综合发现（DAVID）进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，以确定 OA 治疗的关键靶点。基于 Cytoscape 软件版本 3.6.1，构建了“中药药物-活性化合物-靶标-疾病”的可视化网络和 WTD 治疗 OA 的关键靶标蛋白-蛋白相互作用网络。对核心活性化合物和 WTD 治疗 OA 的关键靶标进行了分子对接和验证。
分析发现 WTD 中有 140 种活性化合物，其中 123 种化合物共有 163 个对应靶标。此外，还获得了 331 个差异表达基因和 227 个 OA 相关靶标。鉴定出 32 个关键靶标之间的相互作用网络。WTD 治疗 OA 的生物学过程主要涉及炎症因子的调节、遗传物质的转录、细胞周期、血管生成和内分泌调节。涉及的信号通路主要包括 TNF 信号通路、类风湿关节炎信号通路、癌症相关信号通路、血管内皮生长因子信号通路和破骨细胞分化信号通路。分子对接显示，包括槲皮素和山奈酚在内的 7 种核心化合物与 WTD 治疗 OA 的关键靶蛋白具有很强的亲和力。
WTD 多成分可通过多途径治疗 OA。其活性化合物，包括槲皮素和山奈酚，可通过作用于 TNF、PTGS2、MMP2、IL-6、IL-1β 等关键靶标，调节炎症、免疫、自噬和内分泌相关信号通路，发挥对 OA 的治疗作用。
