Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis

Abstract

To explore the pharmacological mechanism of naringin (NRG) in renal fibrosis (RF) based on network pharmacology combined with molecular docking and experimental validation. We used databases to screen for the targets of NRG and RF. The “drug-disease network” was established using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of targets were performed using Metascape, and molecular docking was performed using Schrödinger. We established an RF model in both mice and cells to validate the results of network pharmacology. After screening the database, we identified 222 common targets of NRG and RF and established a target network. Molecular docking showed that the target AKT had a good interaction with NRG. We found that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway was enriched by multiple targets and served as a target for experimental validation through GO and KEGG. The results revealed that NRG ameliorated renal dysfunction, reduced the release of inflammatory cytokines, decreased the expression of α-SMA, collagen I, and Fn, and recovered the expression of E-cad by inhibiting the PI3K/AKT signaling pathway. Our study used pharmacological analysis to predict the targets and mechanisms of NRG against RF. Furthermore, experiments proved that NRG inhibited RF effectively by targeting the PI3K/AKT signaling pathway.

Potential of Plant-Derived Compounds in Preventing and Reversing Organ Fibrosis and the Underlying Mechanisms

“…These approaches can rapidly identify potential signaling pathways impacted by these compounds and predict their therapeutic efficacy and potential side effects. Recent studies have utilized network pharmacology and molecular docking to help reveal mechanisms by which naringin prevents renal fibrosis [ 149 ]. After database screening, over two hundred common targets were identified for naringin and renal fibrosis.…”

The underlying regulatory mechanisms of colorectal carcinoma by combining Vitexin and Aspirin: based on systems biology, molecular docking, molecular dynamics simulation, and in vitro study

“…Network pharmacology, which studies the pharmacodynamic mechanisms of action of active compounds by constructing and resolving drug-target-disease biological network enrichment relationships, has been applied to study the synergistic and complementary nature of traditional Chinese medicine (TCM) and the relationship between multiple targets and multiple mechanisms of action in TCM ( 25 , 26 ). Molecular docking is another new approach used in TCM research to predict ligand-target interactions at the molecular level and is widely used in drug discovery to identify therapeutically significant letter compounds ( 27 ). It is a promising research direction from the perspective of network pharmacology and molecular docking.…”