The effect of on acute kidney injury: a network pharmacology and molecular docking study.

BACKGROUND

Acute kidney injury (AKI) is a devastating clinical syndrome with high mortality rate attributed to lack of effective treatment. The herbal pair of (AR) and (RAS) is a commonly prescribed herbal formula or is added to other traditional Chinese medicine (TCM) prescriptions for the treatment of kidney diseases. AR-RAS has certain protective effects on AKI in experiments, but the relevant mechanisms have yet to be clear. So this study aims to explore the mechanism of action of AR-RAS in AKI by combining network pharmacology and molecular docking methods.

METHODS

In Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the major AR-RAS chemical components and associated action targets were found and screened. The DrugBank and GeneCards databases were used to find AKI-related targets. The targets that are in close relationship with AKI were obtained from Therapeutic Target database (TTD), Online Mendelian Inheritance in Man (OMIM), and PharmGKB databases. The "herb-active ingredient-target" network was drawn by Cytoscape 3.8.0 software. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to build the protein-protein interaction network. Bioconductor/R was used to examine Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. AR-RAS components and critical targets were docked using the AutoDock Vina program.

RESULTS

A compound-target network, built by screening and analyzing the results, allowed to identify 19 active components and 101 possible therapeutic targets for AKI. The main ingredients were quercetin, kaempferol, 7-o-methylisocronulatol, formononetin and isorhamnetin. The key targets included AKT serine/threonine kinase 1 (AKT1), nuclear receptor coactivator 1 (NCOA1), JUN, estrogen receptor alpha (ESR1) and mitogen-activated protein kinase 8 (MAPK8). These molecules are targeted by pathways such as the calcium signaling route, the tumor necrosis factor (TNF) signaling pathway and the interleukin-17 (IL-17) signaling pathway, as well as the development of T helper 17 cells. Molecular docking demonstrated that AR-active RAS components exhibited strong binding activities to probable targets of AKI.

CONCLUSIONS

We described here the potential active ingredients, possible targets responsible for the efficacy of AR-RAS in AKI treatment, providing a theoretical basis for further research.