Wen JS, Pan ZW, Yao XD, Liu YQ, Zhu YD. Pristimerin ameliorates spasmolytic polypeptide-expressing metaplasia by modulating Cdkn1c (p57)-mediated glycolytic reprogramming. World J Gastroenterol 2026; 32(10): 113771 [DOI: 10.3748/wjg.v32.i10.113771]
Corresponding Author of This Article
Yao-Dong Zhu, MD, Chief Physician, Department of Integrated Traditional Chinese and Western Medicine Oncology, First Affiliated Hospital of Anhui Medical University, No. 120 Wanshui Road, High-tech Zone, Hefei 230000, Anhui Province, China. zhuyaodong2022@126.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Jun-Song Wen, Zi-Wei Pan, Xue-Dan Yao, Yao-Dong Zhu, Department of Integrated Traditional Chinese and Western Medicine Oncology, First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
Yan-Qing Liu, Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou 225000, Jiangsu Province, China
Author contributions: Wen JS, Pan ZW and Zhu YD designed and coordinated the study; Wen JS, Pan ZW, Yao XD and Liu YQ performed the experiments, acquired and analyzed data; Wen JS, Pan ZW, Yao XD, Liu YQ and Zhu YD interpreted the data; Wen JS and Zhu YD wrote the manuscript; Liu YQ and Zhu YD reviewed the manuscript; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82274355; and Key Project for the Cultivation of Outstanding Young Teachers in Anhui Province’s Colleges and Universities, No. 2023-385.
Institutional review board statement: The study does not involve any human experiments.
Institutional animal care and use committee statement: All animal experiments strictly complied with ethical standards approved by the Institutional Animal Care and Use Committee of Anhui Medical University (No. LLSC20220294).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Data supporting the findings of this study are available from the corresponding author (zhuyaodong2022@126.com) upon reasonable request.
Corresponding author: Yao-Dong Zhu, MD, Chief Physician, Department of Integrated Traditional Chinese and Western Medicine Oncology, First Affiliated Hospital of Anhui Medical University, No. 120 Wanshui Road, High-tech Zone, Hefei 230000, Anhui Province, China. zhuyaodong2022@126.com
Received: September 10, 2025 Revised: October 31, 2025 Accepted: December 16, 2025 Published online: March 14, 2026 Processing time: 174 Days and 20 Hours
Abstract
BACKGROUND
Spasmolytic polypeptide-expressing metaplasia (SPEM) is a gastric precancerous lesion (GPL) with high malignant potential. The ethyl acetate extract of Celastrus orbiculatus Thunb. effectively ameliorates GPL and gastric cancer progression. Meanwhile, the primary active constituent of this plant, pristimerin, also demonstrates notable antitumor activity.
AIM
To investigate the therapeutic effects of pristimerin on SPEM and its underlying mechanisms.
METHODS
Pristimerin was administered to high-dose tamoxifen-induced SPEM mice to assess its effects on pathological progression, glycolytic reprogramming, and Cdkn1c (p57) expression. Human gastric epithelial (GES-1) cells were treated with tamoxifen and then with pristimerin or 2-deoxy-D-glucose to demonstrate that pristimerin ameliorates SPEM by regulating glycolytic reprogramming. Furthermore, gastric organoids were treated with N-methyl-N’-nitro-N-nitrosoguanidine/Helicobacter pylori, followed by Cdkn1c overexpression or knockdown and then pristimerin, to confirm p57 as the key target through which pristimerin regulates glycolytic reprogramming and reverses SPEM.
RESULTS
Pristimerin effectively ameliorated gastric mucosal damage and oxyntic atrophy induced by high-dose tamoxifen, suppressed the aberrant upregulation of key glycolytic regulators, SPEM-specific markers, and stem cell markers, and upregulated p57 expression. In tamoxifen-induced GES-1 cells, pristimerin exhibited comparable therapeutic effects. Crucially, glycolysis inhibition in GES-1 cells effectively ameliorated tamoxifen-induced SPEM-associated phenotypes. In gastric organoids, Cdkn1c overexpression suppressed glycolytic reprogramming and SPEM phenotype activation, whereas Cdkn1c knockdown attenuated pristimerin-mediated inhibition of glycolysis and amelioration of SPEM.
CONCLUSION
Pristimerin effectively ameliorates gastric mucosal pathological damage and oxyntic atrophy in high-dose tamoxifen-induced SPEM mice, and improves SPEM progression by modulating Cdkn1c (p57)-mediated glycolytic reprogramming.
Core Tip: This study systematically investigated the therapeutic effects of the natural compound pristimerin on spasmolytic polypeptide-expressing metaplasia (SPEM) using a high-dose tamoxifen-induced mouse model, tamoxifen-treated human gastric epithelial cells, and N-methyl-N’-nitro-N-nitrosoguanidine/Helicobacter pylori-induced gastric organoids. It elucidated the underlying mechanism by which pristimerin ameliorates SPEM through regulating Cdkn1c (p57) to suppress glycolytic reprogramming. These findings not only provide novel mechanistic insights into pristimerin treatment for SPEM but also offer a crucial theoretical basis for targeting p57 in SPEM therapy.
