Original Articles

Weimishu prescription (胃糜舒方) alleviates liver-stomach disharmony and chronic gastritis by reducing inflammation and regulating gastric stem cell differentiation

  • Xiaoyun ZOU ,
  • Minmin WEI ,
  • Shouning JIA ,
  • Yongfu QI ,
  • Hailing LI ,
  • Yan LIU ,
  • Xiujuan SHI ,
  • Junru LI
Expand
  • 1 Medical colledge, Qinghai University, Xining 810016, China
    2 Department of Hepatopathy, Qinghai Provincial Hospital of Traditional Chinese Medicine, Xining 810000, China
    3 Department of Cardiology, Qinghai Provincial Hospital of Traditional Chinese Medicine, Xining 810000, China
    4 Department of Reserch Institute of Traditional Chinese Medicine, Qinghai Provincial Hospital of Traditional Chinese Medicine, Xining 810000, China
    5 Department of Pharmacy, Qinghai Provincial Hospital of Traditional Chinese Medicine, Xining 810000, China
    6 Department of Spleen and Stomach Diseases, Qinghai Provincial Hospital of Traditional Chinese Medicine, Xining 810000, China
Pro. LI Junru, Department of Spleen and Stomach Diseases, Qinghai Provincial Hospital of Traditional Chinese Medicine, Xining 810000, China. mlqinghai201314@sina.com;Telephone: +86-13519732841

Received date: 2025-04-14

  Accepted date: 2025-11-20

  Online published: 2026-01-28

Supported by

2023 Traditional Chinese Medicine Innovation Capability Enhancement Project from the National Administration of Traditional Chinese Medicine(no number);2024 Qinghai Province “Kunlun Talents ? High-End Innovative and Entrepreneurial Talents” Top Notch Talent Project(QHKLYC-GDCXCY-2024-152);Study the Mechanism of Weimishu Prescription in the Treatment of Chronic Gastritis with Liver-Stomach Disharmony

Abstract

OBJECTIVE: To investigate the therapeutic effect of Weimishu prescription (胃糜舒方, WMSP) on chronic gastritis with liver-stomach disharmony (CG-LSD) and elucidate its molecular mechanisms involved in regulating the nuclear factor kappa-B (NF-κB) inflammatory response and gastric stem cell (GSC) differentiation.

METHODS: A CG-LSD rat model was established through a combined protocol involving 56% ethanol and tail-clip stimulation. Rats were administered with low-, medium-, or high-dose WMSP, the positive control drug omeprazole, or high-dose WMSP with the NF-κB agonist phorbol 12-myristate 13-acetate (PMA). Histopathological changes were assessed via hematoxylin and eosin and TdT-mediated dUTP nick end labeling staining. Flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay were performed to evaluate the underlying mechanisms.

RESULTS: WMSP significantly increased rat locomotor activity, improved Traditional Chinese Medicine syndrome scores, and ameliorated pathological damage to the gastric mucosa while reducing gastric mucosal epithelial cells apoptosis. WMSP also increased the proportion of Lgr5+Ki67+ cells; upregulated muscle, intestine, and stomach specific transcript 1, sex determining region Y-box 2, sex determining region Y-box 9, and homing cell adhesion molecule; and enhanced the levels of pepsinogen C, somatostatin, mucin-6, H+-K+ATPase, and E-cadherin proteins, thereby promoting gastric stem cell survival and differentiation. Furthermore, WMSP alleviated systemic and gastric mucosal inflammation in CG-LSD rats. Mechanistically, WMSP suppressed NF-κB expression, thereby reducing Smad-specific E3 ubiquitin ligase 2 levels, which enhanced β-catenin and subsequently increased myelocytomatosis oncogene, and axis inhibition protein 2 expression. PMA administration reversed the protective effect of WMSP on CG-LSD rats.

CONCLUSIONS: WMSP ameliorated gastric mucosal injury in CG-LSD rats by regulating the NF-κB/β-catenin signaling pathway, thereby suppressing inflammation and promoting gastric stem cell differentiation. These findings highlight the therapeutic potential of WMSP, providing the foundation for further clinical evaluations of WMSP in CG-LSD treatment.

Cite this article

Xiaoyun ZOU , Minmin WEI , Shouning JIA , Yongfu QI , Hailing LI , Yan LIU , Xiujuan SHI , Junru LI . Weimishu prescription (胃糜舒方) alleviates liver-stomach disharmony and chronic gastritis by reducing inflammation and regulating gastric stem cell differentiation[J]. Journal of Traditional Chinese Medicine, 2026 , 46(1) : 95 -109 . DOI: 10.19852/j.cnki.jtcm.2026.01.009

References

1. Wang B, Xiao L, Chen P, et al. Uncovering the role of Traditional Chinese Medicine in immune-metabolic balance of gastritis from the perspective of cold and hot: Jin Hong Tablets as a case study. Chin Med 2024; 19: 134.
2. Liu Y, Huang T, Wang L, et al. Traditional Chinese Medicine in the treatment of chronic atrophic gastritis, precancerous lesions and gastric cancer. J Ethnopharmacol 2025; 337: 118812.
3. Yang YY, Li KM, Xu GF, et al. Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: a multicenter real-world study in China. World J Gastroenterol 2024; 30: 1108-20.
4. Shi Y, Wei N, Wang K, et al. Deep learning-assisted diagnosis of chronic atrophic gastritis in endoscopy. Front Oncol 2023; 13: 1122247.
5. Xu W, Jiang T, Shen K, et al. GADD45B regulates the carcinogenesis process of chronic atrophic gastritis and the metabolic pathways of gastric cancer. Front Endocrinol (Lausanne) 2023; 14: 1224832.
6. Chinese Society of Gastroenterology, Cancer Collaboration Group of Chinese Society of Gastroenterology, Chinese Medical Association. Guidelines for diagnosis and treatment of chronic gastritis in China (2022, Shanghai). J Dig Dis 2023; 24: 150-80.
7. Aziz F, Chakraborty A, Liu K, et al. Gastric tumorigenesis induced by combining Helicobacter pylori infection and chronic alcohol through IL-10 inhibition. Carcinogenesis 2022; 43: 126-39.
8. Wang L, Lian YJ, Dong JS, et al. Traditional Chinese Medicine for chronic atrophic gastritis: efficacy, mechanisms and targets. World J Gastroenterol 2025; 31: 102053.
9. Kuang W, Xu J, Xu F, et al. Current study of pathogenetic mechanisms and therapeutics of chronic atrophic gastritis: a comprehensive review. Front Cell Dev Biol 2024; 12: 1513426.
10. Wang B (Tang dynasty). Huang Di Nei Jing Su Wen. Beijing: People's Medical Publishing House, 2013: 8.
11. Luo HY, Shen JW, Li JR, Jin DW, Guan YX, Li YS. Summary of clinical experience of Chief Physician Li Junru in the treatment of chronic atrophic gastritis in plateau areas. Zhong Guo Yi Yao Dao Bao 2024; 21: 143-7.
12. Chen L, Wei S, He Y, et al. Treatment of chronic gastritis with Traditional Chinese Medicine: pharmacological activities and mechanisms. Pharmaceuticals (Basel) 2023; 16: 1308.
13. Yuxi G, Ze LI, Nan C, et al. High-throughput sequencing analysis of differential microRNA expression in the process of blocking the progression of chronic atrophic gastritis to gastric cancer by Xianglian Huazhuo formula. J Tradit Chin Med 2024; 44: 703-12.
14. Yuan C, Xiaosi Z, Junxiang LI, et al. Hewei Jiangni granule alleviates visceral hypersensitivity of non-erosive reflux diseasestromal interaction molecule 1/transient receptor potential vanilloid subfamily member 1 pathway. J Tradit Chin Med 2025; 45: 1-12.
15. Mengting L, Tao LI, Fuhao C, et al. Weichang' an pill alleviates functional dyspepsia through modulating brain-gut peptides and gut microbiota. J Tradit Chin Med 2024; 44: 1177-86.
16. Xu WW, Li JR. Brief analysis of Li Junru's experience in diagnosis and treatment of chronic erosive gastritis. Shi Jie Zui Xin Yi Xue Xin Xi Wen Zhai 2018; 18: 176-81.
17. Xu WW, Li JR, Cui XS. 30 Cases of chronic erosive gastritis with liver depression and Qi stagnation treated with modified Weimishu prescription. Zhong Guo Min Jian Liao Fa 2018; 26: 32-33.
18. Li JR, Xu WW, Zou XY, et al. Clinical study on treatment with Yiqi Huayu Shengji decoction for chronic erosive gastritis patients with Qi deficiency and blood stasis syndrome in Qinghai area. Zhong Yi Za Zhi 2018; 59: 2117-19+47.
19. Guan YX, Luo HY, Li JR. Effects of Weimishu prescription on gastric function and inflammatory response in chronic erosive gastritis with hepato-gastric disharmony patients. Zhong Guo Min Jian Liao Fa 2024; 32: 78-81.
20. Liu M, Liu Q, Zou Q, et al. The composition and roles of gastric stem cells in epithelial homeostasis, regeneration, and tumorigenesis. Cell Oncol (Dordr) 2023; 46: 867-83.
21. Lee SH, Won Y, Gibbs D, et al. Amphiregulin switches progenitor cell fate for lineage commitment during gastric mucosal regeneration. Gastroenterology 2024; 167: 469-84.
22. He L, Zhang X, Zhang S, et al. H. Pylori-facilitated TERT/Wnt/β-Catenin triggers spasmolytic polypeptide-expressing metaplasia and oxyntic atrophy. Adv Sci (Weinh) 2025; 12: e2401227.
23. McGowan KP, Delgado E, Hibdon ES, Samuelson LC. Differential sensitivity to Wnt signaling gradients in human gastric organoids derived from corpus and antrum. Am J Physiol Gastrointest Liver Physiol 2023; 325: G158-g73.
24. Alvina FB, Chen TC, Lim HYG, Barker N. Gastric epithelial stem cells in development, homeostasis and regeneration. Development 2023; 150: dev201494.
25. Li K, Ma X, Li Z, et al. A Natural peptide from a Traditional Chinese Medicine has the potential to treat chronic atrophic gastritis by activating gastric stem cells. Adv Sci (Weinh) 2024; 11: e2304326.
26. Takada H, Sasagawa Y, Yoshimura M, et al. Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis. Nat Commun 2023; 14: 3750.
27. Wang YR, Yan XE, Ding MY, et al. Research on the signaling pathway and the related mechanism of Traditional Chinese Medicine intervention in chronic gastritis of the "inflammation-cancer transformation". Front Pharmacol 2024; 15: 1338471.
28. Liu J, Zhuang Y, Wu J, et al. IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα. Acta Pharm Sin B 2022; 12: 651-64.
29. Xie Y, Zheng L, Chen W, Zeng Y, Yao K, Zhou T. Potential signal pathways and therapeutic effects of mesenchymal stem cell on oxidative stress in diseases. Curr Pharm Des 2024; 31: 83-94.
30. Yu Q, Shi H, Ding Z, Wang Z, Yao H, Lin R. The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation in Helicobacter pylori-associated gastritis by regulating ROS and autophagy. Cell Commun Signal 2023; 21: 1.
31. State Pharmacopoeia Committee. Chinese Pharmacopoeia. Beijing: China Medical Science and Technology Press, 2025: 1-415.
32. Liu F, Nong X, Qu W, Li X. Pharmacokinetics and tissue distribution of 12 major active components in normal and chronic gastritis rats after oral administration of Weikangling capsules. J Ethnopharmacol 2023; 316: 116722.
33. Wang XX, Liu XJ, Wang YJ, et al. Chaihu Shugan powder inhibits interstitial cells of cajal mitophagy through USP 30 in the treatment of functional dyspepsia. J Ethnopharmacol 2024; 323: 117695.
34. Hou LW, Fang JL, Zhang JL, et al. Auricular vagus nerve stimulation ameliorates functional dyspepsia with depressive-like behavior and inhibits the hypothalamus-pituitary-adrenal axis in a rat model. Dig Dis Sci 2022; 67: 4719-31.
35. Qi L, Chang Y, Jintong Y, et al. Association of miR-499 rs3746444, miR-149 rs2292832 polymorphisms and their expression levels with helicobacter pylori-related gastric diseases and Traditional Chinese Medicine syndromes. J Tradit Chin Med 2024; 44: 1024-34.
36. Liu J, Zhang G, Wang Y, et al. Screening and verification of hemostatic effective components group of Panax Notoginseng based on spectrum-effect relationships. J Ethnopharmacol 2024; 321: 117539.
37. Zhang YY, Chen ZJ, Chen LP, et al. Astragali radix (Huangqi): a time-honored nourishing herbal medicine. Chin Med 2024; 19: 119.
38. Chen R, Wang X, Xu H, Zhao R, Hu Q. Comparative study on volatile oils among Bupleuri Radix species and habitats: Yields, chemical characterization and antipyretic activities. Chem Biodivers 2022; 19: e202200549.
39. Zhu Y, Lai Y. Pharmacological properties and derivatives of saikosaponins-a review of recent studies. J Pharm Pharmacol 2023; 75: 898-909.
40. Li YG, Wang XY, Chen HF, Yuan JB, Meng Y, Yang WL. Comparison of the chemical constituents of raw Fructus Aurantii and Fructus Aurantii stir-baked with bran, and the biological effects of auraptene. J Ethnopharmacol 2021; 269: 113721.
41. Nascakova Z, He J, Papa G, Francas B, Azizi F, Müller A. Helicobacter pylori induces the expression of Lgr5 and stem cell properties in gastric target cells. Life Sci Alliance 2024; 7: e202402783.
42. Chen F, Han Y, Yue J, et al. Oxidative stress and Kras mutation in Mist1+ cells act in a double-hit manner to drive gastric tumorigenesis. Cell Rep 2025; 44: 116014.
43. Dong J, Wu X, Zhou X, et al. Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Protein Cell 2023; 14: 433-47.
44. Huang KK, Ma H, Chong RHH, et al. Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression. Cancer Cell 2023; 41: 2019-37.e8.
45. Chen Q, Weng K, Lin M, et al. SOX9 modulates the transformation of gastric stem cells through biased symmetric cell division. Gastroenterology 2023; 164: 1119-36.e12.
46. Huang W, Wen F, Gu P, et al. The inhibitory effect and mechanism of Yi-qi-hua-yu-jie-du decoction on the drug resistance of gastric cancer stem cells based on ABC transporters. Chin Med 2022; 17: 93.
47. Chen Z, Gao Y, Zhang P, et al. Identification of gastric cancer stem cells with CD44 and Lgr 5 double labelling and their initial roles on gastric cancer malignancy and chemotherapy resistance. Cell Biol Toxicol 2024; 41: 12.
48. Qin Y, Geng JX, Huang B. Clinical value of serum pepsinogen in the diagnosis and treatment of gastric diseases. World J Gastrointest Oncol 2023; 15: 1174-81.
49. Papantoniou K, Aggeletopoulou I, Pastras P, Triantos C. The role of somatostatin in the gastrointestinal tract. Biology (Basel) 2025; 14: 558.
50. Arai J, Hayakawa Y, Tateno H, et al. Impaired glycosylation of gastric mucins drives gastric tumorigenesis and serves as a novel therapeutic target. Gastroenterology 2024; 167: 505-21.e19.
51. Della Bella C, Antico A, Panozzo MP, et al. Gastric Th17 cells specific for H+/K+-ATPase and serum IL-17 signature in gastric autoimmunity. Front Immunol 2022; 13: 952674.
52. Tang Y, Yang G, Zhang J, et al. E-cadherin is required for the homeostasis of Lgr5+ gastric antral stem cells. Int J Biol Sci 2019; 15: 34-43.
53. Lialios P, Alimperti S. Role of E-cadherin in epithelial barrier dysfunction: implications for bacterial infection, inflammation, and disease pathogenesis. Front Cell Infect Microbiol 2025; 15: 1506636.
54. Wen X, Qin J, Zhang X, et al. MEK-mediated CHPF2 phosphorylation promotes colorectal cancer cell proliferation and metastasis by activating NF-κB signaling. Cancer Lett 2024; 584: 216644.
55. Bordin F, Terriaca G, Apostolico A, et al. SMURF1 and SMURF 2 directly target GLI1 for ubiquitination and proteasome-dependent degradation. Cell Death Discov 2024; 10: 498.
56. Guo L, Li K, Ma Y, et al. MicroRNA-322-5p targeting Smurf2 regulates the TGF-β/Smad pathway to protect cardiac function and inhibit myocardial infarction. Hum Cell 2024; 37: 972-85.
Outlines

/