Background. Systemic lupus erythematosus (SLE) is a refractory immune disease, which is often complicated with osteonecrosis of the femoral head (ONFH). Curcumin, the most active ingredient of Curcuma longa with a variety of biological activities, has wide effects on the body system. The study is aimed at exploring the potential therapeutic targets underlying the effect of curcumin on SLE-ONFH by utilizing a network pharmacology approach and molecular docking strategy. Methods. Curcumin and its drug targets were identified using network analysis. First, the Swiss target prediction, GeneCards, and OMIM databases were mined for information relevant to the prediction of curcumin targets and SLE-ONFH-related targets. Second, the curcumin target gene, SLE-ONFH shared gene, and curcumin-SLE-ONFH target gene networks were created in Cytoscape software followed by collecting the candidate targets of each component by R software. Third, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Eventually, a gene-pathway network was constructed and visualized by Cytoscape software; key potential central targets were verified and checked by molecular docking and literature review. Results. 201 potential targets of curcumin and 170 related targets involved in SLE-ONFH were subjected to network analysis, and the 36 intersection targets indicated the potential targets of curcumin for the treatment of SLE-ONFH. Additionally, for getting more comprehensive and accurate candidate genes, the 36 potential targets were determined to be analyzed by network topology and 285 candidate genes were obtained finally. The top 20 biological processes, cellular components, and molecular functions were identified, when corrected by a value ≤ 0.05. 20 related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni value ≤ 0.05. Molecular docking showed that the top three genes (TP53, IL6, VEGFA) have good binding force with curcumin; combined with literature review, some other genes such as TNF, CCND1, CASP3, and MMP9 were also identified. Conclusion. The present study explored the potential targets and signaling pathways of curcumin against SLE-ONFH, which could provide a better understanding of its effects in terms of regulating cell cycle, angiogenesis, immunosuppression, inflammation, and bone destruction.

中文翻译：

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探索姜黄素对系统性红斑狼疮股骨头坏死的潜在靶点和机制的网络药理学和分子对接策略

背景。系统性红斑狼疮（SLE）是一种难治性免疫性疾病，常并发股骨头坏死（ONFH）。姜黄素是姜黄中最有效的成分，具有多种生物活性，对人体系统有广泛的作用。该研究旨在通过利用网络药理学方法和分子对接策略探索姜黄素对 SLE-ONFH 影响的潜在治疗靶点。方法. 使用网络分析确定姜黄素及其药物靶点。首先，从瑞士目标预测、GeneCards 和 OMIM 数据库中挖掘与预测姜黄素目标和 SLE-ONFH 相关目标相关的信息。其次，在 Cytoscape 软件中创建姜黄素靶基因、SLE-ONFH 共享基因和姜黄素-SLE-ONFH 靶基因网络，然后通过 R 软件收集每个组件的候选靶标。第三，通过基因本体论（GO）和京都基因和基因组百科全书（KEGG）途径富集分析检查靶点和富集途径。最终，通过 Cytoscape 软件构建并可视化了一个基因通路网络；通过分子对接和文献综述对关键潜在中心靶点进行了验证和检查。结果. 对涉及SLE-ONFH的201个姜黄素潜在靶点和170个相关靶点进行网络分析，36个交叉靶点表明姜黄素治疗SLE-ONFH的潜在靶点。此外，为了获得更全面、更准确的候选基因，确定了36个潜在靶点，通过网络拓扑分析，最终得到285个候选基因。当校正值≤ 0.05 时，前 20 个生物过程、细胞成分和分子功能被确定。当根据 Bonferroni 进行校正时，通过 KEGG 分析确定了 20 条相关的信号通路值≤0.05。分子对接显示，前三个基因（TP53、IL6、VEGFA）与姜黄素具有良好的结合力；结合文献回顾，还鉴定了一些其他基因，如TNF、CCND1、CASP3和MMP9。结论。本研究探讨了姜黄素对抗 SLE-ONFH 的潜在靶点和信号通路，这可以更好地了解其在调节细胞周期、血管生成、免疫抑制、炎症和骨破坏方面的作用。