Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Curr Pharm Des. 2024;30(28):2244-2256. doi: 10.2174/0113816128305808240529115047.
In recent years, the incidence and prevalence of Nephrotic Syndrome (NS) have been increasing. Zhuling Decoction (ZLD), a classical Chinese medicine, has been clinically proven to be effective for the treatment of NS. However, its underlying mechanism and pharmacodynamic substances remain unclear.
This study aimed to explore the mechanism of action and chemical components of ZLD against NS using network pharmacology and molecular docking.
Traditional Chinese Medicine Systems Pharmacology (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicines (BATMAN-TCM), and SwissTargetPrediction databases were used to screen the principal ingredients and the associated targets of ZLD. NS-related targets were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, Therapeutic Target Database (TTD), and Drugbank databases. Shared targets were derived by the intersection of ZLD- and NS-associated targets. Protein-interaction relationships were analyzed using the STRING database and Cytoscape. A visualized drug-active compound-target network of ZLD was established using Cytoscape. Analyses of gene enrichment were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed to assess the binding activity between active components and hub targets.
Polyporusterone E, cerevisterol, alisol B, and alisol B 23-acetate were the primary potential ingredients of ZLD. HMGCR, HSD11B1, NOS2, NR3C1, and NR3C2 were the hub targets of ZLD against NS. Molecular docking showed that polyporusterone E, cerevisterol, and alisol B had high binding activities with targets HMGCR, HSD11B1, and NOS2.
In summary, this study suggests that the main active compounds (polyporusterone E, cerevisterol, alisol B) may have important roles for ZLD acting against NS by binding to hub targets (HMGCR, HSD11B1, and NOS2) and modulating PI3K-Akt, Ras, MAPK, and HIF-1 signaling pathways.
近年来，肾病综合征（NS）的发病率和患病率一直在上升。竹沥饮（ZLD）作为一种经典的中药，已被临床证明对 NS 的治疗有效。然而，其潜在的机制和药效物质仍不清楚。
本研究旨在通过网络药理学和分子对接技术探讨 ZLD 治疗 NS 的作用机制和化学组成。
利用中药系统药理学数据库与分析平台（TCMSP）、中药作用机制生物信息分析工具（BATMAN-TCM）和瑞士药物靶标预测数据库（SwissTargetPrediction）筛选 ZLD 的主要成分及其相关靶点。NS 相关靶点从在线孟德尔遗传数据库（OMIM）、基因卡片数据库（GeneCards）、治疗靶点数据库（TTD）和药物数据库（Drugbank）中获得。通过 ZLD 和 NS 相关靶点的交集获得共享靶点。利用 STRING 数据库和 Cytoscape 软件分析蛋白质相互作用关系。利用 Cytoscape 软件建立 ZLD 的药物活性成分-靶点网络图。利用京都基因与基因组百科全书（KEGG）数据库和 DAVID 数据库对基因富集进行分析。利用分子对接评估活性成分与枢纽靶点的结合活性。
竹沥饮的主要潜在成分有：多孔菌酮 E、麦角甾醇、泽泻醇 B 和泽泻醇 B23-乙酸酯。ZLD 治疗 NS 的枢纽靶点有：HMGCR、HSD11B1、NOS2、NR3C1 和 NR3C2。分子对接显示，多孔菌酮 E、麦角甾醇和泽泻醇 B 与靶点 HMGCR、HSD11B1 和 NOS2 具有较高的结合活性。
综上所述，该研究表明，主要活性化合物（多孔菌酮 E、麦角甾醇、泽泻醇 B）可能通过与枢纽靶点（HMGCR、HSD11B1 和 NOS2）结合，并调节 PI3K-Akt、Ras、MAPK 和 HIF-1 信号通路，对 ZLD 治疗 NS 发挥重要作用。
