Song J, Li DY, Zhang XL, He SS, Wang N, Zhang HC, Bai YJ, Li B, Zhang SS. Chaihu-Shugan-San ameliorates chronic atrophic gastritis by inhibiting nuclear factor-kappa B-mediated inflammation and apoptosis. World J Gastroenterol 2026; 32(10): 115957 [DOI: 10.3748/wjg.v32.i10.115957]
Corresponding Author of This Article
Sheng-Sheng Zhang, MD, Doctor, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Meishuguanhoujie, Dongcheng District, Beijing 100010, China. zhss2000@hotmail.com
Research Domain of This Article
Gastroenterology & Hepatology
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Basic Study
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Mar 14, 2026 (publication date) through Mar 2, 2026
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Publication Name
World Journal of Gastroenterology
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1007-9327
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Song J, Li DY, Zhang XL, He SS, Wang N, Zhang HC, Bai YJ, Li B, Zhang SS. Chaihu-Shugan-San ameliorates chronic atrophic gastritis by inhibiting nuclear factor-kappa B-mediated inflammation and apoptosis. World J Gastroenterol 2026; 32(10): 115957 [DOI: 10.3748/wjg.v32.i10.115957]
World J Gastroenterol. Mar 14, 2026; 32(10): 115957 Published online Mar 14, 2026. doi: 10.3748/wjg.v32.i10.115957
Chaihu-Shugan-San ameliorates chronic atrophic gastritis by inhibiting nuclear factor-kappa B-mediated inflammation and apoptosis
Jin Song, Dan-Yan Li, Xiao-Li Zhang, Sha-Sha He, Ning Wang, Hui-Cun Zhang, Yun-Jing Bai, Bo Li, Sheng-Sheng Zhang
Jin Song, Dan-Yan Li, Sha-Sha He, Ning Wang, Hui-Cun Zhang, Yun-Jing Bai, Bo Li, Sheng-Sheng Zhang, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
Jin Song, Sha-Sha He, Ning Wang, Hui-Cun Zhang, Yun-Jing Bai, Bo Li, Beijing Institute of Chinese Medicine, Beijing 100010, China
Xiao-Li Zhang, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
Co-corresponding authors: Bo Li and Sheng-Sheng Zhang.
Author contributions: Song J designed the study, carried out the experiments, collected data and wrote the draft; Li DY, Zhang XL, He SS and Zhang HC carried out experiments, analyzed the data and edited the paper; Wang N and Bai YJ did the project administration; Zhang SS and Li B supervised this study and co-wrote the paper; all authors proofread and approved the final manuscript.
Supported by the Special Funds of Beijing Institute of Chinese Medicine, No. YJS-2024-20.
Institutional review board statement: This study does not involve any human clinical trials or human participants; it is solely an animal study. Therefore, the corresponding clinical institutional review board approval document is not applicable.
Institutional animal care and use committee statement: This study was approved by the Beijing Institute of Traditional Chinese Medicine Institutional Animal Care and Use Committee with the ethical approval No. BJTCM-R-2025-01-05.
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: All the data in this paper are available from the corresponding author on reasonable request.
Corresponding author: Sheng-Sheng Zhang, MD, Doctor, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Meishuguanhoujie, Dongcheng District, Beijing 100010, China. zhss2000@hotmail.com
Received: November 3, 2025 Revised: December 4, 2025 Accepted: January 7, 2026 Published online: March 14, 2026 Processing time: 119 Days and 8.6 Hours
Abstract
BACKGROUND
Chaihu-Shugan-San (CSS), a classic traditional Chinese medicine formula, has demonstrated significant efficacy in treating various gastrointestinal disorders.
AIM
To explore the therapeutic efficacy of CSS in alleviating chronic atrophic gastritis (CAG), and elucidate the underlying mechanisms of action.
METHODS
High performance liquid chromatography-mass spectrometry was used to identify the main active components of CSS. The therapeutic effects of CSS at doses of 925 mg/kg/day and 1850 mg/kg/day on N-methyl-N’-nitro-N-nitrosoguanidine (MNNG)-induced CAG were evaluated. Network pharmacology and molecular docking were used to predict the potential targets of CSS in CAG. The impact of CSS on the gut microbiota of rats was investigated by 16S rRNA sequencing.
RESULTS
The main active components of CSS were lipids and lipid-like molecules, phenylpropanoids and polyketides. In vivo experiments showed that CSS significantly ameliorated MNNG-induced CAG by inhibiting inflammation and apoptosis. The core target of CSS to alleviate CAG were tumor necrosis factor, interleukin (IL)-1β, IL-6, BAX, BCL2, caspase-3/caspase-9, and NFKBIA. Gene Ontology analysis of these core targets revealed their predominant association with the nuclear factor-kappa B (NF-κB) signaling complex and BAX apoptotic complex. Molecular docking demonstrated that six compounds in CSS, including baicalin, licoisoflavone B, licochalcone B, glabrone, glycyrrhiza flavonol A, and marmin exhibited strong binding affinities with NFKBIA. 16S rRNA sequencing indicated that CSS promoted beneficial changes in the colonic microbial community.
CONCLUSION
CSS alleviated CAG by inhibiting NF-κB-mediated inflammation and apoptosis, providing insights into its mechanism of action in protection against CAG.
Core Tip: Our study demonstrated that Chaihu-Shugan-San (CSS) restored body weight, mitigated gastric tissue histology, and alleviated intestinal metaplasia in rats with chronic atrophic gastritis, reduced levels of inflammatory cytokines, and promoted antiapoptotic pathways. CSS was shown to downregulate the nuclear factor-kappa B signaling proteins, providing insights into its mechanism of action in protection against chronic atrophic gastritis development.
