Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, 210004 Nanjing, Jiangsu, China.
Institute of Pharmaceutical Science, China Pharmaceutical University, 210009 Nanjing, Jiangsu, China.
Front Biosci (Landmark Ed). 2022 Mar 9;27(3):94. doi: 10.31083/j.fbl2703094.
Triptolide (TP) is a major active component of colquhounia root tablet, which has been long been used in China to treat diabetic nephropathy (DN) due to its marked anti‑inflammatory, antiproteinuric, and podocyte‑protective effects.
This study investigated the anti-proteinuria activity and related signaling cascade of TP in DN by utilizing a network pharmacology and molecular docking approach.
From the GeneCard, DisGeNET, and National Center for Biotechnology Information Gene databases, 1458 DN targets were obtained and input together with 303 TP targets into Venny2.1.0 for mapping and comparing. In total, 113 common targets of TP and DN were obtained, of which 7 targets were found to play an important role through theoretical inhibitory constant analysis. The common targets were further analyzed by Kyoto Encyclopedia of Genes and Genomes to identify the pathways related to the therapeutic effect of TP on DN. Among them, the seven targets were found to play key roles in six signaling pathways. The molecular docking results also showed TP had good binding ability to the seven targets.
Analysis of the common targets and key pathways showed that TP can improve DN via its anti-nephritis, anti-renal fibrosis, antioxidant, and podocyte-protective effects, which might elucidate the mechanism by which TP improves renal function and reduces proteinuria in DN.
雷公藤红素(TP)是昆明山海棠片的主要活性成分,由于其具有显著的抗炎、减少蛋白尿和保护足细胞的作用,长期以来一直被中国用于治疗糖尿病肾病(DN)。
本研究通过网络药理学和分子对接方法,研究了 TP 在糖尿病肾病中的抗蛋白尿活性及相关信号级联。
从 GeneCard、DisGeNET 和美国国立生物技术信息中心基因数据库中获得了 1458 个 DN 靶点,并与 303 个 TP 靶点一起输入到 Venny2.1.0 中进行映射和比较。共获得了 113 个 TP 和 DN 的共同靶点,其中通过理论抑制常数分析发现 7 个靶点在其中发挥重要作用。对共同靶点进行京都基因与基因组百科全书分析,确定了与 TP 治疗 DN 疗效相关的途径。其中,这 7 个靶点在 6 个信号通路中发挥关键作用。分子对接结果也表明,TP 对这 7 个靶点具有良好的结合能力。
共同靶点和关键途径的分析表明,TP 可以通过抗肾炎、抗肾纤维化、抗氧化和保护足细胞的作用来改善 DN,这可能阐明了 TP 改善肾功能和减少 DN 蛋白尿的机制。