Jianpiyiqi formula ameliorates chronic atrophic gastritis in rats by modulating the Wnt/β‑catenin signaling pathway

Yan,Zhanpeng; Xu,Tingting; Xu,Yuxuan; Chen,Wanzhen; An,Zhentao; Zhu,Fangshi

doi:10.3892/etm.2021.10310

Jianpiyiqi formula ameliorates chronic atrophic gastritis in rats by modulating the Wnt/β‑catenin signaling pathway

Authors:
- Zhanpeng Yan
- Tingting Xu
- Yuxuan Xu
- Wanzhen Chen
- Zhentao An
- Fangshi Zhu
View Affiliations

Affiliations: Clinical Research Department of Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China
Published online on: June 15, 2021 https://doi.org/10.3892/etm.2021.10310
Article Number: 878
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Jianpiyiqi formula is a Traditional Chinese Medicine (TCM) prescription and is used for the clinical treatment of patients with chronic atrophic gastritis (CAG). The aim of the present study was to examine the underlying mechanisms of Jianpiyiqi formula treatment for CAG via the Wnt/β‑catenin signaling pathway. The high‑performance liquid chromatography (HPLC) chromatogram of Jianpiyiqi formula was constructed. A CAG rat model induced by N‑methyl‑N'‑nitro‑N‑nitrosoguanidine and ranitidine was established. The body weight and food intake of the rats was recorded and rat gastric morphology was visually examined. Pathological analysis of rat gastric tissue was also performed. The levels of gastrin (GAS), pepsin (PP), somatostatin (SS) and prostaglandin E₂ (PGE₂) in rat serum were detected using ELISAs. The expression levels of proteins and genes associated with the Wnt/β‑catenin signaling pathway were measured via immunohistochemistry and reverse transcription‑quantitative PCR. The HPLC chromatogram of Jianpiyiqi formula was determined and as active components, liquiritin and hesperidin were identified from the chromatogram. Compared with the blank group, the body weight and feed intake of the rats were decreased, and gastric mucosal atrophy and inflammation appeared in the model group. Treatment with Jianpiyiqi formula increased the body weight and feed intake of the rats, as well as relieved the gastric atrophy and inflammation. The contents of GAS, PP, SS and PGE₂ were significantly reduced in the model group compared with the blank group. Jianpiyiqi formula significantly increased GAS, PP, SS and PGE₂ levels in serum of rats with CAG. In the model group, Wnt1, β‑catenin and cyclin D1 protein expression levels were increased, and glycogen synthase kinase‑3β (GSK‑3β) protein expression levels were decreased. Jianpiyiqi formula decreased the protein expression levels of Wnt1, β‑catenin and cyclin D1 and increased the protein expression levels of GSK‑3β. Compared with the blank group, the mRNA expression levels of Wnt1, Wnt5a, β‑catenin, cyclin D1 and MMP7 were upregulated, and the mRNA expression levels of GSK‑3β were downregulated in the model group. Treatment with Jianpiyiqi formula downregulated the mRNA expression levels of Wnt1, Wnt5a, β‑catenin, cyclin D1 and MMP7 and upregulated the mRNA expression levels of GSK‑3β. All of the experimental results indicated that Jianpiyiqi formula exerted a therapeutic effect on rats with CAG and inhibited the activation of the Wnt/β‑catenin signaling pathway. Thus, Jianpiyiqi formula, as an effective TCM prescription for treating patients with CAG, may be more widely used in the clinic.

View Figures

View References

1	Li Y, Xia R, Zhang B and Li C: Chronic atrophic gastritis: A review. J Environ Pathol Toxicol Oncol. 37:241–259. 2018.PubMed/NCBI View Article : Google Scholar
2	Rodriguez-Castro KI, Franceschi M, Noto A, Miraglia C, Nouvenne A, Leandro G, Meschi T, De' Angelis GL and Di Mario F: Clinical manifestations of chronic atrophic gastritis. Acta Biomed. 89:88–92. 2018.PubMed/NCBI View Article : Google Scholar
3	Sung J, Kim N, Lee J, Hwang YJ, Kim HW, Chung JW, Kim JW and Lee DH: Associations among Gastric Juice pH, atrophic gastritis, intestinal metaplasia and helicobacter pylori infection. Gut Liver. 12:158–164. 2018.PubMed/NCBI View Article : Google Scholar
4	Lahner E, Zagari RM, Zullo A, Di Sabatino A, Meggio A, Cesaro P, Lenti MV, Annibale B and Corazza GR: Chronic atrophic gastritis: Natural history, diagnosis and therapeutic management. A position paper by the Italian Society of Hospital Gastroenterologists and Digestive Endoscopists [AIGO], the Italian Society of Digestive Endoscopy [SIED], the Italian Society of Gastroenterology [SIGE], and the Italian Society of Internal Medicine [SIMI]. Dig Liver Dis. 51:1621–1632. 2019.PubMed/NCBI View Article : Google Scholar
5	Spence AD, Cardwell CR, McMenamin UC, Hicks BM, Johnston BT, Murray LJ and Coleman HG: Adenocarcinoma risk in gastric atrophy and intestinal metaplasia: A systematic review. BMC Gastroenterol. 17(157)2017.PubMed/NCBI View Article : Google Scholar
6	Annibale B, Esposito G and Lahner E: A current clinical overview of atrophic gastritis. Expert Rev Gastroenterol Hepatol. 14:93–102. 2020.PubMed/NCBI View Article : Google Scholar
7	Su KL, Zhu FS, Shi T, Xu TT, Zhang X and Wang C: Clinical observation on treatment of 62 cases of chronic atrophic gastritis with spleen stomach deficiency syndrome by Weiwei No.1 granule. Pharmacology and Clinics of Chinese Materia Medica. 29:154–156. 2013.(In Chinese).
8	Zhu FS: Theoretical study on the treatment of chronic atrophic gastritis with Jianpi Yiqi Formula. Chinese Journal of Basic Medicine in Traditional Chinese Medicine. 23:471–472+487. 2017.(In Chinese).
9	McCracken KW, Aihara E, Martin B, Crawford CM, Broda T, Treguier J, Zhang X, Shannon JM, Montrose MH and Wells JM: Wnt/beta-catenin promotes gastric fundus specification in mice and humans. Nature. 541:182–187. 2017.PubMed/NCBI View Article : Google Scholar
10	Leushacke M, Tan SH, Wong A, Swathi Y, Hajamohideen A, Tan LT, Goh J, Wong E, Denil SLIJ, Murakami K and Barker N: Lgr5-expressing chief cells drive epithelial regeneration and cancer in the oxyntic stomach. Nat Cell Biol. 19:774–786. 2017.PubMed/NCBI View Article : Google Scholar
11	Tan SH and Barker N: Wnt signaling in adult epithelial stem cells and cancer. Prog Mol Biol Transl Sci. 153:21–79. 2018.PubMed/NCBI View Article : Google Scholar
12	Flanagan DJ, Austin CR, Vincan E and Phesse TJ: Wnt signalling in gastrointestinal epithelial stem cells. Genes (Basel). 9(178)2018.PubMed/NCBI View Article : Google Scholar
13	Yu XW, Xu Q, Xu Y, Gong YH and Yuan Y: Expression of the E-cadherin/β-catenin/tcf-4 pathway in gastric diseases with relation to Helicobacter pylori infection: clinical and pathological implications. Asian Pac J Cancer Prev. 15:215–220. 2014.PubMed/NCBI View Article : Google Scholar
14	Chiurillo MA: Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review. World J Exp Med. 5:84–102. 2015.PubMed/NCBI View Article : Google Scholar
15	Chu A, Yu X, Guo Q, Li Q, Sun M, Yuan Y and Gong Y: H. pylori slyD, a novel virulence factor, is associated with Wnt pathway protein expression during gastric disease progression. Microb Pathog. 148(104428)2020.PubMed/NCBI View Article : Google Scholar
16	Dixon MF, Genta RM, Yardley JH and Correa P: Classification and grading of gastritis. The updated sydney system. International workshop on the histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 20:1161–1181. 1996.PubMed/NCBI View Article : Google Scholar
17	Crafa P, Russo M, Miraglia C, Barchi A, Moccia F, Nouvenne A, Leandro G, Meschi T, De' Angelis GL and Di Mario F: From Sidney to OLGA: An overview of atrophic gastritis. Acta Biomed. 89:93–99. 2018.PubMed/NCBI View Article : Google Scholar
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
19	Berger H, Marques MS, Zietlow R, Meyer TF, Machado JC and Figueiredo C: Gastric cancer pathogenesis. Helicobacter. 21 (Suppl 1):S34–S38. 2016.PubMed/NCBI View Article : Google Scholar
20	Fang WJ, Zhang XY, Yang B, Sui SJ, Chen M, Pan WH, Liao WQ, Zhong M and Wang QC: Chinese herbal decoction as a complementary therapy for atrophic gastritis: A systematic review and meta-analysis. Afr J Tradit Complement Altern Med. 14:297–319. 2017.PubMed/NCBI View Article : Google Scholar
21	Dai YK, Zhang YZ, Li DY, Ye JT, Zeng LF, Wang Q and Hu L: The efficacy of Jianpi Yiqi therapy for chronic atrophic gastritis: A systematic review and meta-analysis. PLoS One. 12(e0181906)2017.PubMed/NCBI View Article : Google Scholar
22	Tian G, Wu C, Li J, Liang B, Zhang F, Fan X, Li Z, Wang Y, Li Z, Liu D, et al: Network pharmacology based investigation into the effect and mechanism of Modified Sijunzi Decoction against the subtypes of chronic atrophic gastritis. Pharmacol Res. 144:158–166. 2019.PubMed/NCBI View Article : Google Scholar
23	Yin J, Yi J, Yang C, Xu B, Lin J, Hu H, Wu X, Shi H and Fei X: Weiqi decoction attenuated chronic atrophic gastritis with precancerous lesion through regulating microcirculation disturbance and HIF-1α signaling pathway. Evid Based Complement Alternat Med. 2019(2651037)2019.PubMed/NCBI View Article : Google Scholar
24	Ji Q, Yang Y, Song X, Han X and Wang W: Banxia Xiexin Decoction in the treatment of chronic atrophic gastritis: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 99(e22110)2020.PubMed/NCBI View Article : Google Scholar
25	Liu Y, Jin Z, Qin X and Zheng Q: Urinary metabolomics research for Huangqi Jianzhong Tang against chronic atrophic gastritis rats based on ¹H NMR and UPLC-Q/TOF MS. J Pharm Pharmacol. 72:748–760. 2020.PubMed/NCBI View Article : Google Scholar
26	Wei F, Jiang X, Gao HY and Gao SH: Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo. Int J Oncol. 51:1383–1394. 2017.PubMed/NCBI View Article : Google Scholar
27	Ahmadi A, Shadboorestan A, Nabavi SF, Setzer WN and Nabavi SM: The role of hesperidin in cell signal transduction pathway for the prevention or treatment of cancer. Curr Med Chem. 22:3462–3471. 2015.PubMed/NCBI View Article : Google Scholar
28	Miwa H, Endo K, Wada R, Hirai S, Hirose M, Misawa H, Nagahara A, Ohta K, Watanabe S and Sato N: Cellular proliferation and differentiation in rat atrophic gastric mucosa induced by N'-methyl-N'-nitro-N-nitrosoguanidine. J Clin Gastroenterol. 25 (Suppl 1):S116–S121. 1997.PubMed/NCBI View Article : Google Scholar
29	Smith JP, Nadella S and Osborne N: Gastrin and gastric cancer. Cell Mol Gastroenterol Hepatol. 4:75–83. 2017.PubMed/NCBI View Article : Google Scholar
30	Schubert ML: Functional anatomy and physiology of gastric secretion. Curr Opin Gastroenterol. 31:479–485. 2015.PubMed/NCBI View Article : Google Scholar
31	Takeuchi K and Amagase K: Roles of cyclooxygenase, prostaglandin E2 and EP receptors in mucosal protection and Ulcer healing in the gastrointestinal tract. Curr Pharm Des. 24:2002–2011. 2018.PubMed/NCBI View Article : Google Scholar
32	Nusse R and Clevers H: Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell. 169:985–999. 2017.PubMed/NCBI View Article : Google Scholar
33	Steinhart Z and Angers S: Wnt signaling in development and tissue homeostasis. Development. 145(dev146589)2018.PubMed/NCBI View Article : Google Scholar
34	Zhao J, Fan Y, Ye W, Feng W, Hu Y, Cai L and Lu B: The protective effect of teprenone on aspirin-related gastric mucosal injuries. Gastroenterol Res Pract. 2019(6532876)2019.PubMed/NCBI View Article : Google Scholar
35	Ajeigbe K, Oladejo E, Emikpe B, Asuk A and Olaleye S: The dual modulatory effect of folic acid supplementation on indomethacin-induced gastropathy in the rat. Turk J Gastroenterol. 23:639–645. 2012.PubMed/NCBI View Article : Google Scholar