Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Ningxia Medical University, Yinchuan, China.
College of Pharmacy, Ningxia Medical University, Yinchuan, China.
Medicine (Baltimore). 2023 Nov 24;102(47):e36196. doi: 10.1097/MD.0000000000036020.
The study aimed to explore the key targets and molecular mechanisms of Dahuang-Tusizi drug pair (DTDP) in the treatment of diabetes nephropathy (DN) based on the GEO database by using network pharmacology combined with molecular docking and immune infiltration. The active components of the DTDP were screened using the Traditional Chinese Medicine Systems Pharmacology database and the Swiss Target Prediction database. The differential genes of DN were retrieved from GEO databases. Next, the intersecting targets of drug and disease were imported into the String database for protein-protein interactions network analysis, and the core targets were identified through topological analysis. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed with the help of the Metascape database and gene set enrichment analysis database. Subsequently, molecular docking was performed to verify the binding activity of the key component and the key target. The Nephroseq V5 database was used to verify the clinical relevance of DN and core genes. Finally, the Using CIBERSORT Algorithm to analyze the immune Infiltration of DN Gene Chip. The network analysis showed that 25 active ingredients of DTDP were associated with 22 targets in DN. The key active ingredients (Sesamin, quercetin, EUPATIN, matrine, beta-sitosterol, isorhamnetin, etc.) and the core targets (JUN, EGF, CD44, FOS, KDR, CCL2, PTGS2, and MMP2) were further identified. Enrichment analysis revealed signaling pathways including TNF, MAPK, and IL-17 signaling pathway. Molecular docking results showed that there was a strong affinity between the key components and core targets. The results of immune infiltration found that the proportion of macrophages in DN tissues was significantly increased. Our findings demonstrated that the characteristics of DTDP in treating DN are "multiple components, multiple targets and multiple pathways." We predicted that DTDP may inhibit inflammation related pathways by regulating key genes, reducing macrophage infiltration. Thus, inhibiting inflammatory response to reduce glomerular damage and delay the development of DN.
该研究旨在基于 GEO 数据库，采用网络药理学结合分子对接和免疫浸润的方法，探讨大黄-菟丝子药对（DTDP）治疗糖尿病肾病（DN）的关键靶点及分子机制。采用中药系统药理学数据库和瑞士靶点预测数据库筛选 DTDP 的活性成分。从 GEO 数据库中检索 DN 的差异基因。接下来，将药物和疾病的交集靶点导入 String 数据库进行蛋白质-蛋白质相互作用网络分析，并通过拓扑分析确定核心靶点。借助 Metascape 数据库和基因集富集分析数据库进行基因本体论分析和京都基因与基因组百科全书富集分析。随后，进行分子对接以验证关键成分和关键靶标的结合活性。使用 Nephroseq V5 数据库验证 DN 和核心基因的临床相关性。最后，使用 CIBERSORT 算法分析 DN Gene Chip 的免疫浸润。网络分析表明，DTDP 的 25 种活性成分与 22 个 DN 靶点相关。关键活性成分（芝麻素、槲皮素、EUPATIN、苦参碱、β-谷甾醇、异鼠李素等）和核心靶点（JUN、EGF、CD44、FOS、KDR、CCL2、PTGS2 和 MMP2）进一步被确定。富集分析揭示了包括 TNF、MAPK 和 IL-17 信号通路在内的信号通路。分子对接结果表明，关键成分与核心靶点之间存在很强的亲和力。免疫浸润结果发现，DN 组织中巨噬细胞的比例明显增加。我们的研究结果表明，DTDP 治疗 DN 的特点是“多成分、多靶点、多途径”。我们预测，DTDP 可能通过调节关键基因抑制炎症相关通路，减少巨噬细胞浸润，从而抑制炎症反应，减少肾小球损伤，延缓 DN 的发展。
