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

Abstract

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.

Ethnobotanical Uses and Pharmacological Activities of Moroccan Ephedra Species

“…It would be interesting to apply network pharmacology approaches to determine how these different metabolites participate and cooperate to promote the activity of the plant extract. This type of approach has proved useful to predict the combinatorial effects of Ephedrae herba components [162,[168][169][170].…”

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“…It would be interesting to apply network pharmacology approaches to determine how these different metabolites participate and cooperate to promote the activity of the plant extract. This type of approach has proved useful to predict the combinatorial effects of Ephedrae herba components [162,[168][169][170].…”

Network Pharmacology and Molecular Docking Study on the Multi-Target Mechanisms of Aloe vera for Non-Alcoholic Steatohepatitis Treatment

“…The core proteins, including AKT1, c-Jun, TNFα, and p53, were used as receptors for molecular docking validation. Quercetin is a flavonol found in many plants and has been demonstrated to bind to AKT1, c-Jun, TNFα, and p53 [41,42]. Our study indicated the presence of quercetin in Aloe vera; therefore, it was chosen as the reference compound to assess the binding affinity between the other eight active ingredients and four core proteins of Aloe vera.…”