Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jul 15, 2024; 15(7): 1562-1588
Published online Jul 15, 2024. doi: 10.4239/wjd.v15.i7.1562
Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease
Mo-Yan Zhang, Shu-Qin Zheng
Mo-Yan Zhang, Liaoning University of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning Province, China
Shu-Qin Zheng, Department of Endocrinology, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China
Author contributions: Zhang MY and Zheng SQ participated in the study design and data collection; Zhang MY performed the data analysis; Zhang MY drafted the manuscript; and Zhang MY and Zheng SQ revised the manuscript; All the authors read and approved the final manuscript.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shu-Qin Zheng, MSc, Associate Professor, Department of Endo-crinology, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33 Beiling Street, Huanggu District, Shenyang 110032, Liaoning Province, China. qxjzsq@sina.com
Received: April 3, 2024
Revised: May 13, 2024
Accepted: May 29, 2024
Published online: July 15, 2024
Processing time: 95 Days and 17 Hours
Abstract
BACKGROUND

Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The Astragalus-Coptis drug pair is frequently employed in the management of DKD. However, the precise molecular mechanism underlying its therapeutic effect remains elusive.

AIM

To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways.

METHODS

The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform. The targets were predicted using the SwissTargetPrediction database, while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database. DKD targets were acquired from the GeneCards, Online Mendelian Inheritance in Man database, and DisGeNET databases, with common targets identified through the Venny platform. The protein-protein interaction network and the “disease-active ingredient-target” network of the common targets were constructed utilizing the STRING database and Cytoscape software, followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients. Gene Ontology (GO) function and Kyoto Ency-clopedia of Genes and Genomes (KEGG) pathway enrichments were performed using the DAVID database. The tissue and organ distributions of key targets were evaluated. PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets. Finally, molecular dynamics (MD) simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins.

RESULTS

A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified. There were 273 common targets between DKD and the Astragalus-Coptis drug pair. Through protein-protein interaction network topology analysis, we identified 9 core active ingredients and 10 key targets. GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes, including protein phosphorylation, negative regulation of apoptosis, inflammatory response, and endoplasmic reticulum unfolded protein response. These pathways are mainly associated with the advanced glycation end products (AGE)-receptor for AGE products signaling pathway in diabetic complications, as well as the Lipid and atherosclerosis. Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets. Notably, the quercetin-AKT serine/threonine kinase 1 (AKT1) and quercetin-tumor necrosis factor (TNF) protein complexes exhibited exceptional stability.

CONCLUSION

This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients, targets, and signaling pathways. We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD. Furthermore, we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF, providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

Keywords: Astragalus membranaceus; Coptis chinensis Franch; Diabetic kidney disease; Network pharmacology; Molecular docking; Molecular dynamics simulation

Core Tip: Network pharmacology, molecular docking, and molecular dynamics simulation studies have demonstrated that diabetic kidney disease (DKD) treatment with the Astragalus-Coptis drug pair involves a diverse range of active ingredients, targets, and pathways. Additionally, quercetin has been found to exhibit strong affinity and binding stability with AKT serine/threonine kinase 1 and tumor necrosis factor, highlighting its potential therapeutic role in DKD. The findings of this study establish a robust theoretical basis for applying the Astragalus-Coptis drug pair in DKD treatment, and these results may provide a guiding framework for further experiments.