Potential Molecular Mechanisms of Ephedra Herb in the Treatment of Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking

• Published in: BioMed research international 2022-07, Vol.2022, p.1-16
• Main Authors: Yao, Tianwen, Wang, Qingliang, Han, Shisheng, Lu, Yan, Xu, Yanqiu, Wang, Yi
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; AKT1 protein; Analysis; Biomedical research; Care and treatment; Chinese medicine; Diagnosis; Disease; Drugs; Edema; Encyclopedias; Ephedra; Genes; Genomes; Health aspects; Health services; Hepatitis B; Herbal medicine; Herbs; IL-1β; Ingredients; Kaempferol; Keywords; Kidney diseases; Ligands; Methods; Molecular docking; Molecular modelling; Molecular targeted therapy; Naringenin; Nephrotic syndrome; Patient outcomes; Pharmacology; Protein interaction; Protein-protein interactions; Proteins; Quercetin; Risk factors; Signal transduction; Signaling; Software; Steroids; Traditional Chinese medicine; Venn diagrams
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2022/9214589

Objective. To explore the possible mechanisms of Ephedra herb (EH) in the treatment of nephrotic syndrome (NS) by using network pharmacology and molecular docking in this study. Methods. Active ingredients and related targets of EH were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the gene names corresponding to the proteins were found through the UniProt database. Then, target genes related to NS were screened out from GeneCards, PharmGKB, and OMIM databases. Next, the intersection targets were obtained successfully through Venn diagram, which were also seen as key target genes of EH and NS. Cytoscape 3.9.0 software was used to construct the effective “active ingredient-target” network diagram, and “drug-ingredient-target-disease (D-I-T-D)” network diagram. After that, the STRING database was used to construct a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment involved in the targets were performed by the DAVID database and ClueGO plugin in Cytoscape. Finally, AutoDockTools software was used for molecular docking to verify the binding strength between main active ingredients and key target proteins. Results. A total of 22 main active ingredients such as quercetin, kaempferol, luteolin, and naringenin were obtained, which could act on 105 targets related to NS. Through PPI network, 53 core targets such as AKT1, TNF, IL6, VEGFA, and IL1B were found, which might play a crucial role in the treatment of NS. Meanwhile, these targets were significantly involved in PI3K-Akt signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway, hepatitis B, and pathways in cancer through GO and KEGG enrichment analysis. The docking results indicated that active ingredients such as kaempferol, luteolin, quercetin, and naringenin all had good binding to the target protein AKT1 or TNF. Among them, luteolin and naringenin binding with AKT1 showed the best binding energy (-6.2 kcal/mol). Conclusion. This study indicated that the potential mechanism of EH in treating NS may be related to PI3K-Akt signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway, which provided better approaches for exploring the mechanism in treating NS and new ideas for further in vivo and in vitro experimental verifications.