Zhao Y, Lu XF, Liu L, Fang H, Sun S, Liu HN, Sun YZ. Dendrobium officinale polysaccharides attenuates spasmolytic polypeptide-expressing metaplasia via dual modulation of gastric epithelial cell fate and macrophage polarization. World J Gastroenterol 2026; 32(45): 122498 [DOI: 10.3748/wjg.122498]
Corresponding Author of This Article
You-Zhi Sun, Professor, School of Chinese Medicine, Jiangxi University of Chinese Medicine, No. 1688 Meiling Avenue, Xinjian District, Nanchang 330004, Jiangxi Province, China. 20040792@jxutcm.edu.cn
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Food Science & Technology
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Zhao Y, Lu XF, Liu L, Fang H, Sun S, Liu HN, Sun YZ. Dendrobium officinale polysaccharides attenuates spasmolytic polypeptide-expressing metaplasia via dual modulation of gastric epithelial cell fate and macrophage polarization. World J Gastroenterol 2026; 32(45): 122498 [DOI: 10.3748/wjg.122498]
World J Gastroenterol. Dec 7, 2026; 32(45): 122498 Published online Dec 7, 2026. doi: 10.3748/wjg.122498
Dendrobium officinale polysaccharides attenuates spasmolytic polypeptide-expressing metaplasia via dual modulation of gastric epithelial cell fate and macrophage polarization
Yi Zhao, Xue-Feng Lu, Lu Liu, Hong Fang, Shuo Sun, Hong-Ning Liu, You-Zhi Sun
Yi Zhao, Xue-Feng Lu, Lu Liu, Hong Fang, Shuo Sun, Hong-Ning Liu, Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
You-Zhi Sun, School of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Co-corresponding authors: Hong-Ning Liu and You-Zhi Sun.
Author contributions: Zhao Y designed the study, created the figures, and drafted the manuscript; Lu XF conducted the experiments, performed data analysis and statistics, created the figures, and also contributed to drafting the manuscript; Liu L and Fang H carried out the experiments and reviewed the data analysis and statistics; Sun S conducted the experiments and verified the data analysis and statistics; Liu HN and Sun YZ designed the study and revised the manuscript for important intellectual content as co-corresponding authors; all of the authors read and approved the final version of the manuscript to be published.
AI contribution statement: Polish the language using Wordvice AI to ensure professionalism and native-like expression.
Supported by National Natural Science Foundation of China, No. 82560860; Jiangxi Provincial Natural Science Foundation Project, No. 20242BAB25562 and No. 20262BAC250038; and National Key R&D Program of China, No. 2024YFE0104600.
Institutional animal care and use committee statement: All animal studies were granted by the Ethics Committee of the Animal Center of Jiangxi University of Chinese Medicine (No. JZLLSC20220606 and date of approval 5/29/2024).
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
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: The data supporting this article have been included within the manuscript. All relevant data are available upon request from the corresponding author.
Corresponding author: You-Zhi Sun, Professor, School of Chinese Medicine, Jiangxi University of Chinese Medicine, No. 1688 Meiling Avenue, Xinjian District, Nanchang 330004, Jiangxi Province, China. 20040792@jxutcm.edu.cn
Received: April 21, 2026 Revised: June 14, 2026 Accepted: July 3, 2026 Published online: December 7, 2026 Processing time: 177 Days and 18.2 Hours
Abstract
BACKGROUND
Spasmolytic polypeptide-expressing metaplasia (SPEM) may serve as an important strategy for preventing intestinal-type gastric cancer, inhibition of STAT6 to inhibit M2 macrophage polarization has been shown to suppress SPEM-associated gene expression and to impede SPEM.
AIM
To further investigate whether Dendrobium officinale polysaccharides (DOP) inhibits the early stages of metaplasia in SPEM by downregulating interleukin (IL)-33 and IL-13 expression, consequently attenuating the IL-13/STAT6 signaling pathway in M2 subtype macrophages.
METHODS
Preventive administration of DOP was conducted for a duration of two weeks prior to model induction. The SPEM mouse model was established through intraperitoneal injections of high concentration of tamoxifen (250 mg/kg) administered over three consecutive days, followed by continued treatment for an additional week. Gastric tissue samples were processed for hematoxylin and eosin staining as well as alcian blue-periodic acid-Schiff staining. Serum levels of IL-13 and IL-33 were quantified using enzyme-linked immunosorbent assay. Immunofluorescence (IF) staining and real-time polymerase chain reaction analyses were employed to evaluate the expression of parietal cell ATPase alpha polypeptide (H+/K+ exchanging alpha polypeptide, ATP4a), the chief cell marker Mist1, the mucous neck cell marker GS II, and the SPEM marker trefoil factor 2. Furthermore, IF staining was utilized to examine the co-expression of aquaporin 5 with gastric intrinsic factor, as well as aquaporin 5 with the proliferation marker Ki67. Both IF and real-time polymerase chain reaction analyses were also performed to assess macrophage polarization markers, including iNOS, CD206, and CD163. Lastly, the impact of DOP on the IL-13/STAT6 signaling pathway was investigated within the SPEM model and in bone marrow-derived macrophages.
RESULTS
DOP was recognized as a protective agent against SPEM. It enhanced the expression of ATP4a and GS II while decreasing the differentiation of chief cells. Mechanistically, DOP inhibited M2 macrophage polarization via the IL-13/STAT6 signaling pathway in both in vivo and in vitro settings, thereby mitigating the onset and progression of SPEM.
CONCLUSION
DOP mitigates SPEM by promoting the activity of parietal and mucous neck cells, suppressing the differentiation of chief cells, and inhibiting M2 macrophage polarization through the IL-13/STAT6 signaling pathway.
Core Tip: Dendrobium officinale polysaccharides upregulated the expression of ATP4a and GS II, while concurrently reducing the differentiation of chief cells. Furthermore, it inhibited M2 macrophage polarization via the IL-13/STAT6 signaling pathway and was identified as a protective agent against spasmolytic polypeptide-expressing metaplasia.
