Department of Nephrology, Shanxi Medical University NO.1 Hospital, Taiyuan, China.
Department of Nephrology, Shanxi Provincial People's Hospital, Taiyuan, China.
PLoS One. 2022 Sep 12;17(9):e0273498. doi: 10.1371/journal.pone.0273498. eCollection 2022.
In this study, we used network pharmacology to explore the possible therapeutic mechanism underlying the treatment of diabetic nephropathy with Yishen capsules.
The active chemical constituents of Yishen capsules were acquired using the Traditional Chinese Medicine Systems Pharmacology platform and the Encyclopedia of Traditional Chinese Medicine. Component target proteins were then searched and screened in the BATMAN database. Target proteins were cross-validated using the Comparative Toxicogenomics Database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the target proteins were performed. Then, protein-protein interaction (PPI) analysis was performed using the STRING database. Finally, a pharmacological network was constructed to show the component-target-pathway relationships. Molecular docking was used to analyse the interaction between drug components and target proteins.
In total, 285 active chemical components were found, including 85 intersection targets against DN. In the pharmacological network, 5 key herbs (A. membranaceus, A. sinensis, E. ferox, A. orientale, and R. rosea) and their corresponding 12 key components (beta-sitosterol, beta-carotene, stigmasterol, alisol B, mairin, quercetin, caffeic acid, 1-monolinolein, kaempferol, jaranol, formononetin, and calycosin) were screened. Furthermore, the 12 key components were related to 24 target protein nodes (e.g., AGT, AKT1, AKT2, BCL2, NFKB1, and SIRT1) and enriched in 24 pathway nodes (such as the NF-kappa B, AGE-RAGE, toll-like receptor, and relaxin signaling pathways). Molecular docking revealed that hydrogen bond was formed between drug components and target proteins.
In conclusion, the active constituents of Yishen capsules modulate targets or signaling pathways in DN pathogenesis.
本研究采用网络药理学方法探讨益肾胶囊治疗糖尿病肾病的可能作用机制。
利用中药系统药理学数据库和分析平台(TCMSP)和中药综合数据库(TCMID)获取益肾胶囊的活性化学成分,然后在BATMAN 数据库中搜索和筛选成分靶标蛋白。使用比较毒理学基因组学数据库(CTD)和京都基因与基因组百科全书(KEGG)对靶标蛋白进行交叉验证,并进行通路分析。然后,使用 STRING 数据库进行蛋白质-蛋白质相互作用(PPI)分析。最后,构建药理学网络以显示成分-靶标-通路关系。采用分子对接分析药物成分与靶蛋白的相互作用。
共发现 285 个活性化学物质,包括 85 个与 DN 相关的交集靶点。在药理学网络中,筛选出 5 种关键草药(膜荚黄芪、当归、刺五加、葛根和玫瑰)及其对应的 12 种关键成分(β-谷甾醇、β-胡萝卜素、豆甾醇、阿魏酸、齐墩果酸、熊果酸、槲皮素、咖啡酸、1-亚油酸甘油酯、山奈酚、贾诺醇、芒柄花素和大豆苷元)。此外,这 12 种关键成分与 24 个靶标蛋白节点相关(如 AGT、AKT1、AKT2、BCL2、NFKB1 和 SIRT1),并富集在 24 个通路节点(如 NF-κB、AGE-RAGE、Toll 样受体和松弛素信号通路)中。分子对接显示药物成分与靶蛋白之间形成氢键。
总之,益肾胶囊的活性成分可调节糖尿病肾病发病机制中的靶标或信号通路。