目的 采用网络药理学研究藤黄健骨胶囊治疗骨性关节炎的有效活性成分及主要作用机制。方法 采用TCMSP、Uniport、DrugBank数据库检索藤黄健骨胶囊的主要化学成分及作用靶点；基于DisGeNET、DrugBank、OMIM及Genecards数据库获取骨性关节炎的相关靶点；将藤黄健骨胶囊与骨性关节炎的靶点取交集，获取藤黄健骨胶囊治疗骨性关节炎的直接靶点；利用STRING数据库得到蛋白相互作用（PPI）网络；使用DAVID数据库进行GO和KEGG富集分析；采用Cytoscape 3.7.2软件构建PPI网络、“药物-活性成分-靶点”网络和“活性成分–重要靶点–关键通路”网络，并进行相关网络分析。结果 初步筛选藤黄健骨胶囊69个成分和257个靶点；骨性关节炎2 655个靶点，药物-疾病交集靶点143个；经过PPI、GO和KEGG富集及相关网络分析，最终得到药物的主要药效成分有槲皮素、木犀草素、山柰酚、β-谷甾醇、芒柄花黄素、甘草查尔酮A、淫羊藿苷元等；关键靶点为PTGS2、TNF、PTGS1、PIK3CG、VEGFA、AKT1、ADRB2、MAPK1、ESR1、MMP2、IL-6、TGFB1等；映射的靶标通路为PI3K-Akt信号通路、NF-κB信号通路、MAPK信号通路、Toll样受体信号通路、破骨细胞分化、FoxO信号通路、HIF-1信号通路、NOD样受体信号通路、雌激素信号通路等；涉及的生物过程主要有凋亡过程的负调控、炎症反应、对缺氧的反应、对雌二醇的反应、细胞对缺氧的反应、ERK1和ERK2级联的正调控、一氧化氮生物合成过程的正调控等。结论 藤黄健骨胶囊主要通过抑制炎症反应、抑制软骨细胞凋亡、调节骨代谢、保护软骨机制及调节软骨下骨代谢平衡途径发挥治疗骨关节炎作用。

Objective To study the active ingredients and main mechanism of Tenghuang Jiangu Capsules in treatment of osteoarthritis based on network pharmacology. Methods Using TCMSP, Uniport, DrugBank databases, the chemical constituents and targets of Tenghuang Jiangu Capsules were screened. Using DisGeNET, and DrugBank, OMIM, and GeneCards databases, the targets of osteoarthritis were retrieved. The intersection of the target of Tenghuang Jiangu Capsules and osteoarthritis was taken to obtain the direct target of the treatment of osteoarthritis with Tenghuang Jiangu Capsules. Protein interaction (PPI) relationship was obtained by using String database. GO analysis and KEGG enrichment analysis were conducted by using the database of DAVID. Cytoscape 3.7.2 software were used to construct and analyse the networks of Protein-protein interaction, "medicine-active components-targets" and "active components-important targets-critical pathways". Results Tenghuang Jiangu Capsules had 69 components and 257 targets. There were 2 655 targets for osteoarthritis and 143 drug-disease intersection targets. Through PPI, GO, KEGG, and related network analysis, the main pharmacodynamic components of the drug were obtained, including quercetin, luteolin, kaempferol, β-sitosterol, formononetin, licorice chalcone A, icariin, etc. The key targets were PTGS2, TNF, PTGS1, PIK3CG, VEGFA, AKT1, ADRB2, MAPK1, ESR1, MMP2, IL-6, TGFB1, etc. The key pathways were PI3K-Akt signaling pathway, NF-κB signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, osteoclast differentiation, FoxO signaling pathway, HIF-1 signaling pathway, NOD receptor signaling pathway, estrogen signaling pathway, etc. The biological processes involved mainly include negative regulation of apoptosis, inflammation, response to hypoxia, response to estradiol, cell response to hypoxia, positive regulation of ERK1 and ERK2 cascade, positive regulation of nitric oxide biosynthesis, etc. Conclusion Tenghuang Jiangu Capsules mainly plays a role in treating osteoarthritis by inhibiting inflammatory reaction, inhibiting chondrocyte apoptosis, regulating bone metabolism, protecting cartilage mechanism and regulating subchondral bone metabolism balance.

R285

河南省科技发展计划项目（202102310191）；河南省高等学校重点科研项目计划（19A320070，21A360026）