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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2023; 15(3): 464-489
Published online Mar 15, 2023. doi: 10.4251/wjgo.v15.i3.464
Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells
Jia-Xiang Zhang, Sheng-Chuan Bao, Juan Chen, Ting Chen, Hai-Liang Wei, Xiao-Yan Zhou, Jing-Tao Li, Shu-Guang Yan
Jia-Xiang Zhang, Sheng-Chuan Bao, Juan Chen, Ting Chen, Shu-Guang Yan, College of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China
Jia-Xiang Zhang, Sheng-Chuan Bao, Juan Chen, Ting Chen, Hai-Liang Wei, Xiao-Yan Zhou, Shu-Guang Yan, Key Laboratory of Gastrointestinal Diseases and Prescriptions in Shaanxi Province, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China
Hai-Liang Wei, Department of General Surgery, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, Shaanxi Province, China
Xiao-Yan Zhou, Department of Gastroenterology, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, Shaanxi Province, China
Jing-Tao Li, Departments of Infectious Disease, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, Shaanxi Province, China
Author contributions: Zhang JX performed the experiments, sample detection, data analysis and wrote the manuscript; Bao SC, Chen J, and Chen T helped with the performing and sample collection of the animal experiment; Yan SG, Li JT, Wei HL, and Zhou XY conceived and supervised the experiments and finalized the manuscript; all authors reviewed the manuscript.
Supported by the Shaanxi Science and Technology overall Planning and Innovation Project, No. 2016KTTSSF01-05; Key R & D projects in Shaanxi Province, No. 2022ZDLSF05-10; and Shaanxi University of Chinese Medicine Discipline Innovation Team Construction Project, No. 2019-YL-05.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Regulations for the Care and Use of Laboratory Animals in Shaanxi University of Chinese Medicine (Approval No. SCXK 2019-0004).
Conflict-of-interest statement: The authors declare that there is no conflict of interest in this study.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at ysg2002. student@sina.com upon reasonable request.
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: Shu-Guang Yan, PhD, Professor, College of Basic Medicine, Shaanxi University of Traditional Chinese Medicine, Century Avenue, Qindu District, Xianyang 712046, Shaanxi Province, China. ysg2002.student@sina.com
Received: August 16, 2022
Peer-review started: August 16, 2022
First decision: November 17, 2022
Revised: December 1, 2022
Accepted: January 16, 2023
Article in press: January 16, 2023
Published online: March 15, 2023
ARTICLE HIGHLIGHTS
Research background
In recent years, more and more attention has been paid to the research of gastric precancerous lesions. Gastric precancerous lesions (GPLs) are an important histopathological stage before the occurrence of gastric cancer (GC). Effective treatment and reversal of it is an important means to prevent GC.
Research motivation
Xiaojianzhong decoction (XJZ) is a classic prescription in ancient China, and it is mostly used clinically to treat gastrointestinal diseases such as chronic atrophic gastritis. This study aimed to explore the in vivo mechanism of XJZ in treating GPL.
Research objectives
To study the effect and mechanism of XJZ on autophagy and glycolysis of GPL gastric mucosal epithelial cells, and provide a theoretical basis for the clinical prevention and treatment of GPL.
Research methods
Using the N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) compound modeling method to construct a model of gastric precancerous lesions in rats, intervene with XJZ, and use a variety of methods to detect the effects of XJZ on autophagy, glycolysis and gastric precancerous lesions in rats.
Research results
The treatment of XJZ can promote the weight gain of rats and improve the pathological manifestations of GPL-related tissues; the formation of autophagosomes and autolysosomes in gastric tissue is reduced, and the expressions of B cell lymphoma/leukemia-2 and adenovirus E1B19000 interacting protein 3, moesin-like BCL2-interacting protein 1, and microtubule associated protein 1 light chain 3 are reduced. The expression of p62 increased, and the level of autophagy was fully inhibited. XJZ inhibited the level of autophagy by activating the phosphatidylinositol 3-kimase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway; while improving gastric mucosal hypoxia, it could also inhibit autophagy and improve abnormal glucose metabolism in gastric mucosal cells. XJZ inhibited the expression of Unc-51 Like kinase 1 (ULK1) to improve abnormal glucose metabolism in gastric mucosa, and prevented the increase of autophagy level by inhibiting p53/AMP-activated protein kinase (AMPK) pathway and ULK1 Ser317555 phosphorylation.
Research conclusions
Xiaojianzhong Decoction has a therapeutic effect on MNNG-induced gastric precancerous lesions, which may be achieved through the joint regulation of PI3K/AKT/mTOR, p53/AMPK/ULK1 signaling pathways and gastric mucosal hypoxia.
Research perspectives
This study mainly explores Xiaojianzhong Decoction regulates PI3K/AKT/mTOR, p53/AMPK/ULK1 signaling pathways and gastric mucosal hypoxia to improve gastric precancerous lesions in rats.
