Copyright
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification
Meng-Ying Che, Ling Yuan, Jiao Min, Duo-Jie Xu, Dou-Dou Lu, Wen-Jing Liu, Kai-Li Wang, Yan-Yan Wang, Yi Nan
Meng-Ying Che, Jiao Min, Wen-Jing Liu, Yi Nan, Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Ling Yuan, College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Duo-Jie Xu, Kai-Li Wang, Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Dou-Dou Lu, School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Yan-Yan Wang, Department of Endocrinology, Yinchuan Hospital of Traditional Chinese Medicine, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Author contributions: Che MY conducted most of the experiments, analyzed the data, completed the figure production, and wrote the manuscript; Min J carried out a portion of the experiments and participated in the production of the figures and the composition of the manuscript; Xu DJ and Liu WJ carried out part of the experiments and participated in the statistical analysis of the data; Lu DD and Wang KL performed the network pharmacology prediction; Yuan L and Wang YY designed the study; Nan Y revised and improved the manuscript; all authors approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 81573695, No. 81860894, and No. 81674096; and Ningxia Key Research and Development Plan Project, No. 2021BEG03106.
Institutional review board statement: The study did not involve human or animal experiments.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
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: Yi Nan, MD, Professor, Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, Ningxia Hui Autonomous Region, China. 20080011@nxmu.edu.cn
Received: November 2, 2023
Peer-review started: November 2, 2023
First decision: November 21, 2023
Revised: December 5, 2023
Accepted: January 18, 2024
Article in press: January 18, 2024
Published online: March 15, 2024
ARTICLE HIGHLIGHTS
Research background
Diabetic kidney disease (DKD) is one of the serious complications of diabetes mellitus. It has a poor prognosis and is one of the causes of end-stage renal disease. Existing treatments can improve the symptoms of DKD to some extent. However, they have the disadvantages of side effects and high price.
Research motivation
We performed in vitro cellular experiments to validate the effectiveness of the Nardostachyos Radix et Rhizoma-rhubarb drug pair (NRDP) and to provide new ideas for clinical treatment of DKD.
Research objectives
In this study, we used network pharmacology and molecular docking to predict the targets of NRDP for the treatment of DKD and validated the prediction findings using cellular experiments.
Research methods
Targets for NRDP and DKD were obtained using databases such as TCMSP, Genecards, OMIM, and TTD. Drug-disease intersection targets were obtained based on the VENNY 2.1 database and "drug-component-target-disease" network was constructed. Afterward, Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analyses were performed to further observe the relationship between targets and pathways. Finally, molecular docking was performed on the active ingredients of NRDP. Experiments such as the CCK-8 method, flow cytometry, and Western Blot were used to verify the molecular mechanism of NRDP for DKD.
Research results
NRDP may inhibit the viability of high glucose-induced TCMK-1 cells by modulating the advanced glycation end products (AGEs)-receptor for AGEs (RAGE) signaling pathway, thereby blocking cell cycle progression in the G0/G1 phase and reducing apoptosis. It also downregulated the protein expression of p-STAT3, BAX, Caspase3, and Caspase9, and up-regulated the protein levels of BCL-2 and STAT3. These findings verified that NRDP could reduce high glucose-induced TCMK-1 cell injury, thereby restoring their function.
Research conclusions
NRDP may achieve its therapeutic effect on DKD by modulating the AGE-RAGE signaling pathway. NRDP arrests the cell cycle progression at the G0/G1 phase by inhibiting the proliferation of high glucose-induced TCMK-1 cells and reducing their apoptosis. NRDP inhibits the expression of proteins related to the AGE-RAGE signaling pathway in high glucose environment, which delays the progression of DKD.
Research perspectives
We next plan to conduct in vivo animal and omics experiments. To determine the specific components of NRDP in the blood for the treatment of DKD, gene detection will be performed by high-throughput validation methods such as transcriptomics, in order to provide a safe and effective method for clinical treatment of DKD.
