Research on the Mechanism of Guizhi to Treat Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking Technology

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.

Huoxiang Zhengqi Oral Liquid Attenuates LPS‐Induced Acute Lung Injury by Modulating Short‐Chain Fatty Acid Levels and TLR4/NF‐κB p65 Pathway

“…The rats except the control group were administered a single dose of LPS (5 mg/kg, Escherichia coli 055: B5 L2880, Sigma, USA) intraperitoneally according to a previous study [22]. The rats in the LPS+HZOL groups received an oral administration of the agents for 2 weeks before LPS injection at different doses (LPS+HZOL-L, 1.67 mL/kg, 5-fold of the clinical dose; LPS +HZOL-M, 3.33 mL/kg, 10-fold of the clinical dose; and LPS+HZOL-H, 6.67 mL/kg, 20-fold of the clinical dose) following a previous study [10], while DEX (5 mg/kg) was administrated via stomach perfusion for six days before the LPS treatments [18,23]. The dosage was adjusted according to the body weight of rats.…”

“…At present, network pharmacology can be used to theoretically analyze multiple compounds and targets to predict the therapeutic mechanisms of action of TCMs in relation to treating diseases based on different databases [18]. An increasing number of studies on TCM formulations use network pharmacology to explore their pharmacodynamic mechanism [19,20].…”

Study of molecular mechanisms underlying the medicinal plant Tripterygium wilfordii-derived compound celastrol in treating diabetic nephropathy based on network pharmacology and molecular docking

“…The binding receptor-ligand activity was evaluated by the value of the binding energy. The lower the binding energy is, the more stable is the receptor-ligand binding as per reports (He et al, 2021). In this study, docking pairs that simultaneously met the criteria of binding energy <−5.0 kcal/mol and the formation of hydrogen bonds (Feng et al, 2021) were considered effective docking and reserved for further analysis.…”

Multitarget Mechanism of Artemisia Plants to Fight Respiratory Tract Infections Based on Network Pharmacology and Molecular Docking

“…Artemisia species have complex components, many targets, and a wide range of therapeutic effects and signaling pathways. 15 Network pharmacology integrates diseases and drugs into biomolecular networks to predict their effective components, possible target pathways, and mechanisms of action. 16,17 It has the advantages of a high success rate, fewer side effects, multiple genes, and multiple targets.…”