目的 利用網(wǎng)絡藥理學和分子對接研究大黃治療膝關(guān)節(jié)炎的分子機制。方法 通過TCMSP、PubChem、Swiss數(shù)據(jù)庫收集到大黃的活性成分和潛在作用靶點。利用GeneCards、OMIM、DisGeNET數(shù)據(jù)庫檢索得到膝關(guān)節(jié)炎的相關(guān)靶點。利用Venny 2.1繪制韋恩圖，得到大黃治療膝關(guān)節(jié)炎的交集靶點?；赟TRING數(shù)據(jù)庫，運用Cytoscape 3.10軟件制作“藥物–活性成分–潛在靶點–疾病”網(wǎng)絡圖，用拓撲分析篩選出核心靶點。利用DAVID數(shù)據(jù)庫進行基因本體（GO）富集分析和京都基因與基因組百科全書（KEGG）通路富集分析，并通過Discovery Studio軟件進行分子對接。結(jié)果 共篩選出16個大黃活性成分，包括大黃素、β-谷甾醇、大黃酸、大黃素甲醚等，篩選出蛋白激酶B1（Akt1）、基質(zhì)金屬蛋白酶9（MMP9）、表皮生長因子受體（EGFR）、原癌基因酪氨酸蛋白激酶（SRC）、胱天蛋白酶3（CASP3）等核心靶點。大黃治療膝關(guān)節(jié)炎的信號通路主要富集于癌癥中的蛋白多糖通路、癌癥通路、內(nèi)分泌抵抗通路、前列腺癌通路、表皮生長因子受體信號通路、焦點黏附通路、人類巨細胞感染通路等。分子對接顯示核心成分大黃素、β-谷甾醇、大黃酸、大黃素甲醚等與核心靶點Akt1、MMP9、EGFR、SRC、CASP3等對接程度良好。結(jié)論 大黃中大黃素、大黃酸等有效成分可能通過作用于Akt1、MMP9、EGFR等靶點調(diào)節(jié)多條信號通路，達到治療膝關(guān)節(jié)骨性關(guān)節(jié)炎的作用。

Objective To study the molecular mechanism of Rhei Radix et Rhizoma in treatment of knee osteoarthritis. Methods The active ingredients and potential targets of Rhei Radix et Rhizoma were collected through TCMSP, PubChem, and Swiss databases. GeneCards, OMIM, and DisGeNET databases were used to search the related targets of knee arthritis. The intersection target of Rhei Radix et Rhizoma in treatment of knee arthritis was obtained by using Venny 2.1 to draw Venn diagram. Based on STRING database, the network diagram of “drug - active ingredient - target - disease” was made by Cytoscape 3.10 software, and the core target was selected by topological analysis. DAVID database was used for GO and KEGG pathway enrichment analysis, and molecular docking was performed by Discovery Studio software. Results A total of 16 active components of Rhei Radix et Rhizoma were screened, including emodin, β-sitosterol, rhein, emodin methyl ethol, etc., and core targets such as Akt1, MMP9, EGFR, SRC, CASP3 were screened. The signaling pathways of Rhei Radix et Rhizoma for the treatment of knee arthritis are mainly concentrated in proteoglycan pathway, cancer pathway, endocrine resistance pathway, prostate cancer pathway, epidermal growth factor receptor signaling pathway, focal adhesion pathway, and human giant cell infection pathway. Molecular docking showed that core components emodin, β-sitosterol, rhein, emodin methyl ether and core targets Akt1, MMP9, EGFR, SRC, CASP3, and so on were well docked. Conclusion Active components such as emodin and rhein in Rhei Radix et Rhizoma may regulate multiple signaling pathways by acting on Akt1, MMP9, EGFR and other targets to achieve the therapeutic effect of knee osteoarthritis.

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東莞市社會發(fā)展科技重點項目（20231800935402）