目的 通过网络药理学及分子对接技术探讨豨莶草治疗膝骨关节炎的作用机制。方法 通过中药系统药理学数据库与分析平台（TCMSP）等数据库筛选豨莶草的活性成分及作用靶点，并与膝骨关节炎疾病靶点进行比对，获得共有靶点。构建“药物–活性成分–靶点–疾病”及蛋白质–蛋白质相互作用（PPI）网络，进行网络拓扑分析筛选核心靶点及活性成分。运用基因本体（GO）功能注释及京都基因与基因组百科全书（KEGG）通路富集分析揭示其作用机制。利用分子对接技术验证关键活性成分与核心靶点的结合能力。结果 从TCMSP等数据库中筛选出豨莶草的9种潜在活性成分，包括常春藤皂苷元、豆甾醇、β-谷甾醇等，并确定68个靶点。与膝骨关节炎疾病靶点比对后，获得24个共有靶点。PPI网络及网络拓扑分析筛选出4个核心靶点，即Jun蛋白（JUN）、胱天蛋白酶3（CASP3）、B细胞淋巴瘤2（BCL2）、热休克蛋白90αA1（HSP90AA1）。KEGG通路富集分析显示，这些共有靶点主要涉及NF-κB信号通路、丝裂原活化蛋白激酶（MAPK）信号通路以及NOD样受体蛋白3（NLRP3）炎症小体通路等。分子对接实验结果表明，豆甾醇与BCL2结合能最低，为−7.9 kJ/mol，具有较强的结合亲和力。结论 豨莶草的多种活性成分通过作用于JUN、CASP3等核心靶点，调控炎症、细胞凋亡等多条信号通路，发挥抗炎、保护软骨等作用。

Objective To explore the mechanism of Siegesbeckia Herba in treating knee osteoarthritis based on network pharmacology and molecular docking. Methods The active components and their targets of Siegesbeckia Herba were screened through databases such as traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and compared with the targets of knee osteoarthritis to obtain common targets. A “drug-active component-target-disease” network and a protein-protein interaction (PPI) networks were constructed. Network topology analysis was used to screen core targets and active components. Gene Ontology (GO) function annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were used to reveal its mechanism of action. Molecular docking technology was used to verify the binding ability of key active components with core targets. Results Nine potential active components of Siegesbeckia Herba were screened from databases such as TCMSP, including hederagenin, stigmasterol, beta-sitosterol, etc., and 68 targets were identified. After comparison with the targets of knee osteoarthritis, 24 common targets were obtained. PPI network and network topology analysis screened out four core targets, namely Jun protein (JUN), Caspase-3 (CASP3), B-cell lymphoma 2 (BCL2), and heat shock protein 90 alpha family class A member 1 (HSP90AA1). KEGG pathway enrichment analysis showed that these common targets were mainly involved in the NF-κB signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome pathway. Molecular docking results showed that stigmasterol had the lowest binding energy with BCL2, at −7.9 kJ/mol, indicating a strong binding affinity. Conclusion Multiple active components of Siegesbeckia Herba act on core targets like JUN and CASP3, regulating multiple signaling pathways such as inflammation and apoptosis, and exerting anti-inflammatory and cartilage-protective effects.

R285.5

黑龙江中医药大学国家级项目配套项目（2019PT08）；天津市滨海新区中医医院科技项目（bhzy2024z02）；天津中医药大学骨伤研究所开放课题（2024GSQ01）