目的 通過網(wǎng)絡(luò)藥理學及分子對接技術(shù)探討豨薟草治療膝骨關(guān)節(jié)炎的作用機制。方法 通過中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺（TCMSP）等數(shù)據(jù)庫篩選豨薟草的活性成分及作用靶點，并與膝骨關(guān)節(jié)炎疾病靶點進行比對，獲得共有靶點。構(gòu)建“藥物–活性成分–靶點–疾病”及蛋白質(zhì)–蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，進行網(wǎng)絡(luò)拓撲分析篩選核心靶點及活性成分。運用基因本體（GO）功能注釋及京都基因與基因組百科全書（KEGG）通路富集分析揭示其作用機制。利用分子對接技術(shù)驗證關(guān)鍵活性成分與核心靶點的結(jié)合能力。結(jié)果 從TCMSP等數(shù)據(jù)庫中篩選出豨薟草的9種潛在活性成分，包括常春藤皂苷元、豆甾醇、β-谷甾醇等，并確定68個靶點。與膝骨關(guān)節(jié)炎疾病靶點比對后，獲得24個共有靶點。PPI網(wǎng)絡(luò)及網(wǎng)絡(luò)拓撲分析篩選出4個核心靶點，即Jun蛋白（JUN）、胱天蛋白酶3（CASP3）、B細胞淋巴瘤2（BCL2）、熱休克蛋白90αA1（HSP90AA1）。KEGG通路富集分析顯示，這些共有靶點主要涉及NF-κB信號通路、絲裂原活化蛋白激酶（MAPK）信號通路以及NOD樣受體蛋白3（NLRP3）炎癥小體通路等。分子對接實驗結(jié)果表明，豆甾醇與BCL2結(jié)合能最低，為−7.9 kJ/mol，具有較強的結(jié)合親和力。結(jié)論 豨薟草的多種活性成分通過作用于JUN、CASP3等核心靶點，調(diào)控炎癥、細胞凋亡等多條信號通路，發(fā)揮抗炎、保護軟骨等作用。

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

黑龍江中醫(yī)藥大學國家級項目配套項目（2019PT08）；天津市濱海新區(qū)中醫(yī)醫(yī)院科技項目（bhzy2024z02）；天津中醫(yī)藥大學骨傷研究所開放課題（2024GSQ01）