Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2022; 13(8): 622-642
Published online Aug 15, 2022. doi: 10.4239/wjd.v13.i8.622
In vivo evaluation and mechanism prediction of anti-diabetic foot ulcer based on component analysis of Ruyi Jinhuang powder
Xiu-Yan Li, Xiao-Tong Zhang, Yi-Cheng Jiao, Hang Chi, Ting-Ting Xiong, Wen-Jing Zhang, Mi-Nan Li, Yan-Hong Wang
Xiu-Yan Li, Yi-Cheng Jiao, Hang Chi, Ting-Ting Xiong, Wen-Jing Zhang, Mi-Nan Li, Yan-Hong Wang, Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
Xiu-Yan Li, College of Pharmacy, Harbin Medical University, Harbin 150040, Heilongjiang Province, China
Xiao-Tong Zhang, Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Ministry of Education, College of Pharmacy, Harbin 150040, Heilongjiang Province, China
Author contributions: Li XY, Zhang XT, Jiao YC, Chi H, Xiong TT and Zhang WJ, Li MN performed the experiments and acquired and analyzed the data; Li XY, Zhang XT and Wang YH wrote the manuscript; all authors approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 82074025; Scientific Research Project of Heilongjiang Health Committee, No. 2020-293; and Scientific and Technological Innovation Project for College Students of Heilongjiang University of Chinese Medicine, No. 2021-13.
Institutional review board statement: This study does not involve human.
Institutional animal care and use committee statement: This study was approved by Ethics Committee of Heilongjiang University of Chinese Medicine, Harbin, China.
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: Yan-Hong Wang, MD, Teacher, Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Xiangfang District, Harbin 150040, Heilongjiang Province, China. 799378826@qq.com
Received: May 6, 2022
Peer-review started: May 6, 2022
First decision: May 30, 2022
Revised: June 10, 2022
Accepted: July 6, 2022
Article in press: July 6, 2022
Published online: August 15, 2022
Abstract
BACKGROUND

Diabetes is a metabolic disease with a high complication rate. Diabetic foot ulcers (DFUs) seriously affect the quality of life of patients. A total of 15%-20% of diabetic patients develop DFUs, which heal with difficulty over a long time and can result in amputation and disability. Traditional Chinese medicine has a unique effect in the treatment of skin ulcerative diseases. Ruyi Jinhuang powder (RHP) is one of the classic prescriptions in traditional Chinese medicine and is widely used in clinical practice.

AIM

To verify the ability of RHP to promote wound healing by electron microscopy analysis in animal models and hematoxylin-eosin (HE) staining. The effective components of RHP were extracted and identified by gas chromatography-mass spectrometry (GC-MS), and the obtained chemical components were analyzed by network pharmacology methods to predict its therapeutic mechanism.

METHODS

Sprague Dawley rats were injected with streptozotocin to establish the DFU model. HE staining was used to observe the wound tissue under an electron microscope. The chemical constituents of RHP were extracted first by supercritical fluid extraction and alcohol extraction, and then, GC-MS and ultra-performance liquid chromatography–MS were used to separately identify the chemical constituents. In addition, the "herb-component-target" link was established through the Traditional Chinese Medicine Systems Pharmacology database to obtain the target information, and the molecular docking of important components and key targets was performed in Discovery Studio software. Cytoscape software was used to visualize and analyze the relationship between the chemical composition, targets and Traditional Chinese Medicine network.

RESULTS

RHP promoted DFU healing in rats by affecting fibroblasts and nerve cells. A total of 89 chemical components were obtained by GC-MS. Network pharmacological analysis revealed that RHP was associated with 36 targets and 27 pathways in the treatment of DFU, of which the important components were luteolin, trans caryophyllene, ar-turmerone, palmitic acid, methyl palmitate, gallic acid, demethoxycurcumin, berberine, and rheic acid. The key targets were posttranscriptional silencing, topoisomerase II alpha, muscarinic acetylcholine receptor M2, interleukin 6, tumor necrosis factor and retinoic X receptor alpha, and the key pathways were the phosphoinositide 3-kinase-protein kinase B signaling pathway, neuroactive ligand–receptor interactions, and the forkhead box O signaling pathway.

CONCLUSION

Our results indicated that RHP may play a role in the treatment of DFU through these target pathways by affecting insulin resistance, altering the nervous system and immune system, participating in inflammatory responses and regulating cell proliferation, differentiation and apoptosis through other specific mechanisms.

Keywords: Ruyi Jinhuang powder, Diabetic foot ulcer, Mass spectrometry-chromatography, Network pharmacology, Hematoxylin-eosin staining, Components analysis

Core Tip: Although some studies have suggested that Ruyi Jinhuang powder (RHP) has a therapeutic effect on diabetic foot ulcers (DFUs), few have used component analysis, investigated the mechanism of action, and utilized wound-healing experiments. The components of RHP were used to predict the mechanism of action, and wound healing was observed by establishing a DFU rat model to further prove the therapeutic effect of RHP on DFU to finally determine a possible mechanism of action.