Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 3158-3168
Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3158
Yiqi Jiedu Huayu decoction inhibits precancerous lesions of chronic atrophic gastritis by inhibiting NLRP3 inflammasome-mediated pyroptosis
Peng Zhou, Zi-Han Zheng, Tao Wan, Chuan-Wen Liao, Jie Wu
Peng Zhou, Zi-Han Zheng, Tao Wan, Chuan-Wen Liao, Jie Wu, Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
Author contributions: Zhou P conceived the study; Zheng ZH and Wan T performed the experiments; Zhou P analyzed, Liao CW and Wu J interpreted the data. All authors contributed to the biological analysis, interpretation of the results, read and approved the final version of the manuscript.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of Jiangxi Provincial People's Hospital.
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 Jiangxi Provincial People's Hospital, No. KT086.
Conflict-of-interest statement: All authors agree with the presented findings, have contributed to the work, and declare no conflict of interest.
Data sharing statement: All the data used to support the findings of this study are included within the article.
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: Jie Wu, MBBS, Chief Nurse, Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No. 152 Aiguo Road, Donghu District, Nanchang 330006, Jiangxi Province, China. 3051385961@qq.com
Received: December 15, 2023
Revised: April 25, 2024
Accepted: May 17, 2024
Published online: July 15, 2024
Processing time: 210 Days and 13 Hours
Abstract
BACKGROUND

Chronic atrophic gastritis (CAG) is a prevalent chronic gastritis usually accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The increasing application of traditional Chinese medicine in CAG treatment has shown promising results with low side effects and significant efficacy.

AIM

To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG.

METHODS

A CAG rat model was established by Helicobacter pylori bacteria solution combined with N-methyl-N’-nitro-N-nitrosoguanidine. Histopathological measurements were conducted by hematoxylin-eosin and alcian blue and periodic acid-Schiff staining. Serum levels of inflammatory factors and gastric mucosal-related factors were examined using enzyme-linked immunosorbent assay. Protein and mRNA levels were quantified via western blot and quantitative real-time polymerase chain reaction analysis, respectively. Molecular interaction was verified by chromatin immunoprecipitation (ChIP) assay.

RESULTS

YJHD greatly attenuated pathological changes in the gastric mucosa and precancerous lesions in CAG rats. Meanwhile, YJHD treatment reduced serum levels of inflammatory factors [interleukin (IL)-6, tumor necrosis factor-α and C-reactive protein] and increased serum levels of gastric mucosal-related factors (gastrin, pepsin, somatostatin and prostaglandin E2) in CAG rats. In addition, YJHD administration suppressed NLRP3 inflammasome-mediated cell pyroptosis, as well as the activation of TLR4/NF-κB and IL-6/STAT3 signaling pathways. Mechanically, ChIP experiments confirmed that NLRP3 transcription was regulated by TLR4/NF-κB and IL-6/STAT3 signaling.

CONCLUSION

Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.

Keywords: Chronic atrophic gastritis, Yiqi Jiedu Huayu decoction, NLRP3, Pyroptosis

Core Tip: Yiqi Jiedu Huayu decoction (YJHD), an empirical formula comprising multiple traditional Chinese medicines, has demonstrated efficacy in preventing and treatment of human gastrointestinal tumors. However, its impact on precancerous lesion of gastric cancer (PLGC) remains poorly understood, making this study significant. Here, we found that YJHD treatment markedly inhibited PLGC. Additionally, our experiments indicated that YJHD inhibited NLRP3 inflammasome formation and pyroptosis of epithelial cells in chronic atrophic gastritis by deactivating the TLR4/NF-κB and IL-6/STAT3 pathways.