Abstract
Objective Nephrotic syndrome (NS) is a common glomerular disease caused by a variety of causes and is the second most common kidney disease. Guizhi is the key drug of Wulingsan in the treatment of NS. However, the action mechanism remains unclear. In this study, network pharmacology and molecular docking were used to explore the underlying molecular mechanism of Guizhi in treating NS. Methods The active components and targets of Guizhi were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Hitpick, SEA, and Swiss Target Prediction database. The targets related to NS were obtained from the DisGeNET, GeneCards, and OMIM database, and the intersected targets were obtained by Venny2.1.0. Then, active component-target network was constructed using Cytoscape software. And the protein-protein interaction (PPI) network was drawn through the String database and Cytoscape software. Next, Gene Ontology (GO) and pathway enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. And overall network was constructed through Cytoscape. Finally, molecular docking was conducted using Autodock Vina. Results According to the screening criteria, a total of 8 active compounds and 317 potential targets of Guizhi were chosen. Through the online database, 2125 NS-related targets were identified, and 93 overlapping targets were obtained. In active component-target network, beta-sitosterol, sitosterol, cinnamaldehyde, and peroxyergosterol were the important active components. In PPI network, VEGFA, MAPK3, SRC, PTGS2, and MAPK8 were the core targets. GO and KEGG analyses showed that the main pathways of Guizhi in treating NS involved VEGF, Toll-like receptor, and MAPK signaling pathway. In molecular docking, the active compounds of Guizhi had good affinity with the core targets. Conclusions In this study, we preliminarily predicted the main active components, targets, and signaling pathways of Guizhi to treat NS, which could provide new ideas for further research on the protective mechanism and clinical application of Guizhi against NS.
Highlights
Nephrotic syndrome (NS) is a clinical syndrome defined as massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema [1]
A total of 220 compounds were collected from the TCMSP database, with OB ≥ 30%, DL ≥ 0:18, and Caco − 2 ≥ −0:4, and 7 active compounds were identified
Our previous study found that cinnamaldehyde might be an important active compound of Guizhi [11]
Summary
Nephrotic syndrome (NS) is a clinical syndrome defined as massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema [1]. According to the epidemiological survey, the incidence of NS is about 2-10/100000, and it mostly occurs in male children [2]. NS greatly affects people’s health and life quality with poor prognosis and high recurrence rate [3]. According to traditional Chinese medicine (TCM), NS belongs to “edema,” and the pathogenesis of NS lies in the dysfunction of the lung, spleen, and kidney [4]. TCM has been used to treat kidney disease and its complications, for that it can protect the kidney from dysfunction and delay the renal failure [5]. Guizhi is a Chinese herbal medicine that is commonly used to treat edema [6].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
