The Effect of on Acute Kidney Injury: a Network Pharmacology and Molecular Docking Study

Overview

Journal Transl Androl Urol

Date 2024 Feb 26

PMID 38404557

Authors

Qin Wang

Wenrui Zhen

Giuseppe Lippi

Qi Liu

Affiliations

Soon will be listed here.

Abstract

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.

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