Copyright
©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes
Ling Yang, Yang Jian, Zai-Yuan Zhang, Bao-Wen Qi, Yu-Bo Li, Pan Long, Yao Yang, Xue Wang, Shuo Huang, Jing Huang, Long-Fu Zhou, Jie Ma, Chang-Qing Jiang, Yong-He Hu, Wen-Jing Xiao
Ling Yang, Yu-Bo Li, Xue Wang, Shuo Huang, Yong-He Hu, School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
Yang Jian, Department of Clinical Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
Zai-Yuan Zhang, Jing Huang, Yong-He Hu, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
Bao-Wen Qi, South China Hospital of Shenzhen University, Shenzhen 518116, Guangdong Province, China
Pan Long, Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
Yao Yang, Jie Ma, Chang-Qing Jiang, Wen-Jing Xiao, Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
Long-Fu Zhou, Department of Biomedical Engineering, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
Author contributions: Yang L designed the study, performed the network pharmacological analysis, and wrote the manuscript; Jian Y, Zhang ZY, Qi BW, Jiang CQ, and Yang Y performed the production and identification of SXT; Li YB, Huang S, Huang J, and Ma J performed the animal experiments; Long P performed the statistical analysis; Wang X, Zhou LF, and Hu YH designed the study; Xiao WJ revised the manuscript and approved the final proof as the corresponding author; all authors approved the final version of the article.
Supported by Natural Science Foundation of Sichuan Province, No. 2022NSFSC0738; Basic Research Funds for Central Universities, No. 2682022ZTPY038; and Tibet Autonomous Region Science and Technology Planning Project, No. XZ2022RH001.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of The General Hospital of Western Theater Command (No. 2022ky028-1).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
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: Wen-Jing Xiao, PhD, Doctor, Department of Pharmacy, The General Hospital of Western Theater Command, No. 270 Tianhui Road, Chengdu 610083, Sichuan Province, China.
xwj-4321@163.com
Received: January 20, 2023
Peer-review started: January 20, 2023
First decision: April 11, 2023
Revised: April 14, 2023
Accepted: May 5, 2023
Article in press: May 5, 2023
Published online: July 15, 2023
Processing time: 173 Days and 20.8 Hours
ARTICLE HIGHLIGHTS
Research background
The occurrence of myocardial ischemia/reperfusion injury (MI/RI) in diabetic individuals is often accompanied by larger infarct sizes and diminished cardiac function, which can have significant implications for patient prognosis. However, the effectiveness of strict glycemic control for the purpose of reducing cardiovascular mortality in diabetes was found to be insignificant. Notablely, Shuxin decoction (SXT) has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting.
Research motivation
There is an urgent need to identify and facilitate developing novel complementary or alternative forms of medicine for effectively managing MI/RI with diabetes.
Research objectives
To investigate the protective effects and underlying mechanism of SXT against MI/RI with diabetes.
Research methods
The Traditional Chinese Medicine System Pharmacology Database was employed to identify critical components and potential targets of SXT. Additionally, various databases such as Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB were searched to identify potential therapeutic targets associated with MI/RI in diabetic patients. The intersection of the potential targets of SXT and the therapeutic targets related to MI/RI in diabetic patients were analyzed through bioinformatics techniques using the Database for Annotation, Visualization and Integrated Discovery. Subsequently, the major results of the bioinformatics analysis were validated through animal experiments.
Research results
Through animal experiments, it was demonstrated that the hypothesis generated by network pharmacology pertaining to the potential of the SXT to ameliorate MI/RI in diabetes through the reduction of oxidized low density lipoprotein (ox-LDL) and inhibition of the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway was valid. The administration of a dose of SXT (2.8 g/kg/day) led to a decline in ox-LDL, AGEs, and RAGE, along with modulation of blood lipid levels. Furthermore, the treatment resulted in a decrease in the expression of apoptosis-related proteins such as Bax and cleaved caspase 3, while increasing the expression of Bcl-2.
Research conclusions
SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.
Research perspectives
The potential utilization of SXT as a complementary or alternative medicinal intervention could represent a valuable strategy for effectively managing MI/RI in diabetes.
