Drug Res (Stuttg) 2013; 63(11): 597-602
DOI: 10.1055/s-0033-1341518
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Effect of Astragalus Polysaccharides on Chronic Atrophic Gastritis Induced by N-methyl-N′-nitro-N-nitrosoguanidine in Rats

X. Zhu
1   Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
S. Liu
1   Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
J. Zhou
2   Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
H. Wang
1   Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
R. Fu
1   Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
X. Wu
1   Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
J. Wang
2   Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
F. Lu
3   Providence, Brown University, Rhode Island, USA
› Author Affiliations
Further Information

Publication History

received 24 August 2012

accepted 15 March 2013

Publication Date:
11 September 2013 (online)


This study investigated the effect and mechanism of Astragalus polysaccharides (APS) on chronic atrophic gastritis (CAG) induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in rats. Histomorphological, hormone-level, and immunohistochemistry experiments were used to investigate the gastric mucosal injury. Pathological changes were readily found in CAG rats. Compared to the control rats, the CAG rats showed significantly decreased plasma levels of gastrin and somatostatin while their motilin levels increased. Moreover, PGE2 in gastric tissue increased and serum sIgA decreased significantly, while the GSH/GSSG ratio showed no change. Immunohistochemical detection showed that the expression of EGFR, COX-2, and MMP-2 was higher in the gastric tissue of CAG rats. After APS treatment, the gastric morphology of CAG rats improved. APS increased plasma gastrin and somatostatin levels significantly but had no significant effect on the motilin level. APS also decreased tissue PGE2 and increased serum sIgA in CAG rats without affecting the GSH/GSSH ratio. This study suggested that APS had a beneficial effect on CAG rats by deregulating EGFR at its downstream effectors COX-2 and MMP-2.

  • References

  • 1 Giannakis M, Chen SL, Karam SM et al. Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc Natl Acad Sci USA 2008; 105: 4358-4363
  • 2 Kuipers EJ. Review article: exploring the link between Helicobacter pylori and gastric cancer. Aliment Pharmacol Ther 1999; 13 (Suppl. 01) 3-11
  • 3 Ubukata H, Nagata H, Tabuchi T et al. Why is the coexistence of gastric cancer and duodenal ulcer rare? Examination of factors related to both gastric cancer and duodenal ulcer. Gastric Cancer 2011; 14: 4-12
  • 4 Rautelin H, Kosunen TU. Helicobacter pylori infection in Finland. Ann Med 2004; 36: 82-88
  • 5 Kim YJ, Chung JW, Lee SJ et al. Progression from chronic atrophic gastritis to gastric cancer; tangle, toggle, tackle with Korea red ginseng. J Clin Biochem Nutr 2010; 46: 195-204
  • 6 Kim DJ, Ahn B, Han BS et al. Potential preventive effects of Chelidonium majis L. (Papaveraceae) herb extract on glandular stomach tumor development in rats treated with N-methyl-N′-nitro-N nitrosoguanidine (MNNG) and hypertonic sodium chloride. Cancer Lett 1997; 112: 203-208
  • 7 Lu B, Xu L, Yu L et al. Extract of radix curcumae prevents gastric cancer in rats. Digestion 2008; 77: 87-91
  • 8 Velmurugan B, Bhuvaneswari V, Nagini S. Antiperoxidative effects of lycopene during N-methyl-N′-nitro-N-nitrosoguanidine-induced gastric carcinogenesis. Fitoterapia 2002; 73: 604-611
  • 9 Velmurugan B, Bhuvaneswari V, Burra UK et al. Prevention of N-methyl-N′-nitro-N-nitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis in Wistar rats by lycopene. Eur J Cancer Prev 2002; 11: 19-26
  • 10 Li J, Zhong Y, Li H et al. Enhancement of Astragalus polysaccharide on the immune responses in pigs inoculated with foot-and-mouth disease virus vaccine. Int J Biol Macromol 2011; 49: 362-368
  • 11 Liu QY, Yao YM, Zhang SW et al Astragalus polysaccharides regulate T cell-mediated immunity via CD11c(high)CD45RB(low) DCs in vitro. J Ethnopharmacol 2011; 136: 457-464
  • 12 Yin X, Chen L, Liu Y et al. Enhancement of the innate immune response of bladder epithelial cells by Astragalus polysaccharides through upregulation of TLR4 expression. Biochem Biophys Res Commun 2010; 397: 232-238
  • 13 Zhou X, Xu Y, Yang G et al. Increased galectin-1 expression in muscle of Astragalus polysaccharide-treated Type 1 diabetic mice. J Nat Med 2011; 65: 500-507
  • 14 Juan YC, Kuo YH, Chang CC et al Administration of a decoction of sucrose- and polysaccharide-rich radix astragali (huang qi) ameliorated insulin resistance and Fatty liver but affected Beta-cell function in type 2 diabetic rats. Evid Based Complement Alternat Med 2011; 2011: 349807
  • 15 Liu M, Wu K, Mao X et al Astragalus polysaccharide improves insulin sensitivity in KKAy mice: regulation of PKB/GLUT4 signaling in skeletal muscle. J Ethnopharmacol 2010; 127: 32-37
  • 16 Wang JJ, Li J, Shi L et al. Preventive effects of a fractioned polysaccharide from a traditional Chinese herbal medical formula (Yu Ping Feng San) on carbon tetrachloride-induced hepatic fibrosis. J Pharm Pharmacol 2010; 62: 935-942
  • 17 Yan F, Zhang QY, Jiao L et al Synergistic hepatoprotective effect of Schisandrae lignans with Astragalus polysaccharides on chronic liver injury in rats. Phytomedicine 2009; 16: 805-813
  • 18 Auyeung KK, Woo PK, Law PC et al. Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells. J Ethnopharmacol 2012; 141: 635-641
  • 19 Na D, Liu FN, Miao ZF et al. Astragalus extract inhibits destruction of gastric cancer cells to mesothelial cells by anti-apoptosis. World J Gastroenterol 2009; 15: 570-577
  • 20 Navarrete A, Arrieta J, Terrones L et al. Gastroprotective effect of Astragaloside IV: role of prostaglandins, sulfhydryls and nitric oxide. J Pharm Pharmacol 2005; 57: 1059-1064
  • 21 Sugimura T, Fujimura S. Tumour production in glandular stomach of rat by N-methyl-N′-nitro-N-nitrosoguanidine. Nature 1967; 216: 943-944
  • 22 Saito T, Inokuchi K, Takayama S et al. Sequential morphological changes in N-methyl-N′-nitro-N-nitrosoguanidine carcinogenesis in the glandular stomach of rats. J Natl Cancer Inst 1970; 44: 769-783
  • 23 Kobori O, Gedigk P, Totovic V. Early changes of glandular stomach in Wistar rats ingesting N-methyl-N′-nitro-N-nitrosoguanidine (MNNG): with special reference to light microscopic, electron microscopic, and enzyme histochemical study of the regenerating epithelium induced by MNNG. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1976; 87: 127-138
  • 24 Marotta F, Hayakawa K, Mikami Y et al. Relationship between gastrin cell number, serum, antral mucosa and luminal gastrin concentration and gastric acidity in antral atrophic gastritis. Gut 1990; 31: 279-281
  • 25 Rindi G, Luinetti O, Cornaggia M et al. Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology 1993; 104: 994-1006
  • 26 Sumii K, Fukushima T, Hirata K et al. Antral gastrin and somatostatin concentrations in peptic ulcer patients. Peptides 1981; 2 (Suppl. 02) 281-283
  • 27 Bortolotti M, Frada G, Vezzadini P et al Influence of gastric acid secretion on interdigestive gastric motor activity and serum motilin in the elderly. Digestion 1987; 38: 226-233
  • 28 Hayashi S, Sugiyama T, Yokota K et al. Analysis of immunoglobulin A antibodies to Helicobacter pylori in serum and gastric juice in relation to mucosal inflammation. Clin Diagn Lab Immunol 1998; 5: 617-621
  • 29 Szaleczky E, Pronai L, Molnar B et al. Increased cell proliferation in chronic Helicobacter pylori positive gastritis and gastric carcinoma--correlation between immuno-histochemistry and Tv image cytometry. Anal Cell Pathol 2000; 20: 131-139
  • 30 Oda K, Matsuoka Y, Funahashi A et al. A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 2005; 1 2005.0010
  • 31 Sheu BS, Yang HB, Sheu SM et al. Higher gastric cycloxygenase-2 expression and precancerous change in Helicobacter pylori-infected relatives of gastric cancer patients. Clin Cancer Res 2003; 9: 5245-5251
  • 32 Konturek PC, Konturek SJ, Brzozowski T. Helicobacter pylori infection in gastric cancerogenesis. J Physiol Pharmacol 2009; 60: 3-21
  • 33 Lim HY, Joo HJ, Choi JH et al. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. Clin Cancer Res 2000; 6: 519-525
  • 34 Sampieri CL, de la Peña S, Ochoa-Lara M et al. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis. World J Gastroenterol 2010; 16: 1500-1505