Archive | 2021
Exploring the Molecular Mechanism of Liuwei Dihuang Pills for Treating Diabetic Nephropathy by Combined Network Pharmacology and Molecular Docking
Abstract
\n Background\n\nDiabetic nephropathy (DN) is a common and serious complication of diabetes, but without a satisfactory treatment strategy till now. Liuwei Dihuang Pills (LDP), an effective Chinese medicinal formula, has been used to treat DN for more than 1000 years. However, its underlying mechanism of action is still vague.\nMethods\n\nActive compounds and corresponding targets of LDP were predicted from the TCMSP database. DN disease targets were extracted from the OMIM, Genecards, TTD, DisGeNET, and DrugBank databases. Subsequently, the herbal-compound-target network and protein-protein interaction (PPI) network were constructed and analyzed via the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analysis were carried out on the Metascape web platform. Molecular docking was utilized AutoDock Vina and PyMOL software.\nResult\n\n41 active components and 186 corresponding targets of LDP were screened out. 131 common targets of LDP and DN were acquired. Quercetin, kaempferol, beta-sitosterol, diosgenin, and stigmasterol could be defined as five crucial compounds. JUN, MAPK8, AKT1, EGF, TP53, VEGFA, MMP9, MAPK1, and TNF might be nine key targets. Enrichment analysis showed that common targets were mainly associated with inflammation reaction, oxidative stress, immune regulation, and cell apoptosis. AGE-RAGE and IL-17 were suggested two significant signal pathways. Molecular docking revealed that the nine key targets could closely bind to their corresponding active compounds.\nConclusion\n\nThe present study fully reveals the multi-compounds and multi-targets characteristics of LDP in DN treatment. Furthermore, this study provides valuable evidence for further scientific research of pharmacological mechanisms and broader clinical application.