Skip to main content

Advertisement

SpringerLink
Log in

Gastroprotective Action of Cochinchina Momordica Seed Extract Is Mediated by Activation of CGRP and Inhibition of cPLA2/5-LOX Pathway

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Cochinchina momordica seed extract (SK-MS10), which is composed of the major compounds momordica saponins, has been evaluated for its gastroprotective effects in rat models of acute gastric mucosal damage. Ethanol and water immersion restraint stress (WRS) induced gastric damage, including hemorrhages and edema, was significantly attenuated by pretreatment with SK-MS10. In addition, SK-MS10 reduced increases of mucosal myeloperoxidase (MPO), IL-1β, and TNFα levels and the expression of cPLA2, and 5-LOX induced by ethanol or WRS. SK-MS10 also increased hexosamine, adherent mucus, and the expression of MUC5AC. Furthermore, SK-MS10 enhanced the mucosal expression of the CGRP gene and its serum levels. N G-methyl L-arginine (L-NMMA) or capsaicin desensitization reversed the SK-MS10-induced gastroprotection effect. These results suggest that SK-MS10 is a gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, down-regulating cPLA2, 5-LOX, and increasing the synthesis of mucus. Furthermore, CGRP-NO pathway was found to play an important role in these gastroprotective effects of SK-MS10.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Akiba Y, Guth PH, Engel E, Nastaskin I, Kaunitz JD. Dynamic regulation of mucus gel thickness in rat duodenum. Am J Physiol Gastrointest Liver Physiol. 2000;279:G437–G447.

    CAS  PubMed  Google Scholar 

  2. Akiba Y, Furukawa O, Guth PH, Engel E, Nastaskin I, Kaunitz JD. Sensory pathways and cyclooxygenase regulate mucus gel thickness in rat duodenum. Am J Physiol Gastrointest Liver Physiol. 2001;280:G470–G474.

    CAS  PubMed  Google Scholar 

  3. Ichikawa T, Ishihara K, Kusakabe T, Hiruma H, Kawakami T, Hotta K. CGRP modulates mucin synthesis in surface mucus cells of rat gastric oxyntic mucosa. Am J Physiol Gastrointest Liver Physiol. 2000;279:G82–G89.

    CAS  PubMed  Google Scholar 

  4. Holzer P, Livingston EH, Saria A, Guth PH. Sensory neurons mediate protective vasodilatation in rat gastric mucosa. Am J Physiol. 1991;260:G363–G370.

    CAS  PubMed  Google Scholar 

  5. Holzer P. Neural emergency system in the stomach. Gastroenterology. 1998;114:823–839. doi:10.1016/S0016-5085(98)70597-9.

    Article  CAS  PubMed  Google Scholar 

  6. Lambrecht N, Burchert M, Respondek M, Muller KM, Peskar BM. Role of calcitonin gene-related peptide and nitric oxide in the gastroprotective effect of capsaicin in the rat. Gastroenterology. 1993;104:1371–1380.

    CAS  PubMed  Google Scholar 

  7. Gao XM. Mu Bie Zi (Semen momordicae). Chinese Materia Medicia. Beijing: Traditional Chinese Materia Medica Press; 2005;601–602.

  8. Matsuda H, Li Y, Murakami T, Yamahara J, Yoshikawa M. Protective effects of oleanolic acid oligoglycosides on ethanol- or indomethacin-induced gastric mucosal lesions in rats. Life Sci. 1998;63:PL245–PL250. doi:10.1016/S0024-3205(98)00426-3.

    Article  CAS  PubMed  Google Scholar 

  9. Harada N, Okajima K, Uchiba M, Katsuragi T. Contribution of capsaicin-sensitive sensory neurons to stress-induced increases in gastric tissue levels of prostaglandins in rats. Am J Physiol Gastrointest Liver Physiol. 2003;285:G1214–G1224.

    CAS  PubMed  Google Scholar 

  10. Nam SY, Kim N, Lee CS, et al. Gastric mucosal protection via enhancement of MUC5AC and MUC6 by geranylgeranylacetone. Dig Dis Sci. 2005;50:2110–2120. doi:10.1007/s10620-005-3016-8.

    Article  CAS  PubMed  Google Scholar 

  11. Lacy ER, Ito S. Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin. Gastroenterology. 1982;83:619–625.

    CAS  PubMed  Google Scholar 

  12. Kitagawa H, Takeda F, Kohei H. A simple method for estimation of gastric mucus and effects of antiulcerogenic agents on the decrease in mucus during water-immersion stress in rats. Arzneimittelforschung. 1986;36:1240–1244.

    CAS  PubMed  Google Scholar 

  13. Nishida K, Ohta Y, Ishiguro I. Teprenone, an anti-ulcer agent, increases gastric mucosal mucus level via nitric oxide in rats. Jpn J Pharmacol. 1998;78:519–522. doi:10.1254/jjp.78.519.

    Article  CAS  PubMed  Google Scholar 

  14. Van Klinken BJ, Dekker J, Buller HA, Einerhand AW. Mucin gene structure and expression: protection vs. adhesion. Am J Physiol. 1995;269:G613–G627.

    PubMed  Google Scholar 

  15. Ho SB, Roberton AM, Shekels LL, Lyftogt CT, Niehans GA, Toribara NW. Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression. Gastroenterology. 1995;109:735–747. doi:10.1016/0016-5085(95)90380-1.

    Article  CAS  PubMed  Google Scholar 

  16. Ho SB, Shekels LL, Toribara NW, et al. Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. Cancer Res. 1995;55:2681–2690.

    CAS  PubMed  Google Scholar 

  17. Wallace JL, Miller MJ. Nitric oxide in mucosal defense: a little goes a long way. Gastroenterology. 2000;119:512–520. doi:10.1053/gast.2000.9304.

    Article  CAS  PubMed  Google Scholar 

  18. Rokutan K, Teshima S, Kawai T, et al. Geranylgeranylacetone stimulates mucin synthesis in cultured guinea pig gastric pit cells by inducing a neuronal nitric oxide synthase. J Gastroenterol. 2000;35:673–681. doi:10.1007/s005350070046.

    Article  CAS  PubMed  Google Scholar 

  19. Holzer P. Role of visceral afferent neurons in mucosal inflammation and defense. Curr Opin Pharmacol. 2007;7:563–569. doi:10.1016/j.coph.2007.09.004.

    Article  CAS  PubMed  Google Scholar 

  20. Vongthavaravat V, Mesiya S, Saymeh L, Xia Y, Harty RF. Mechanisms of transforming growth factor-alpha (TGF-alpha) induced gastroprotection against ethanol in the rat: roles of sensory neurons, sensory neuropeptides, and prostaglandins. Dig Dis Sci. 2003;48:329–333. doi:10.1023/A:1021935728607.

    Article  PubMed  Google Scholar 

  21. Kato K, Yang H, Tache Y. Role of peripheral capsaicin-sensitive neurons and CGRP in central vagally mediated gastroprotective effect of TRH. Am J Physiol. 1994;266:R1610–R1614.

    CAS  PubMed  Google Scholar 

  22. Fukushima K, Aoi Y, Kato S, Takeuchi K. Gastro-protective action of lafutidine mediated by capsaicin-sensitive afferent neurons without interaction with TRPV1 and involvement of endogenous prostaglandins. World J Gastroenterol. 2006;12:3031–3037.

    CAS  PubMed  Google Scholar 

  23. Brzozowski T, Konturek PC, Drozdowicz D, et al. Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence. Inflammopharmacol. 2005;13:45–62. doi:10.1163/156856005774423971.

    Article  CAS  Google Scholar 

  24. Brzozowski T, Konturek PC, Drozdowicz D, et al. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways. World J Gastroenterol. 2005;11:6450–6458.

    PubMed  Google Scholar 

  25. Zayachkivska OS, Konturek SJ, Drozdowicz D, Konturek PC, Brzozowski T, Ghegotsky MR. Gastroprotective effects of flavonoids in plant extracts. J Physiol Pharmacol. 2005;56(Suppl 1):219–231.

    PubMed  Google Scholar 

  26. Guidobono F, Pagani F, Sibilia V, Soglian A, Rapetti D, Netti C. The role of sensory neurons in the antiulcer effect of centrally injected amylin in rat. Peptides. 2000;21:1537–1541. doi:10.1016/S0196-9781(00)00308-9.

    Article  CAS  PubMed  Google Scholar 

  27. Ren J, Gao J, Ojeas H, et al. Involvement of capsaicin-sensitive sensory neurons in stress-induced gastroduodenal mucosal injury in rats. Dig Dis Sci. 2000;45:830–836. doi:10.1023/A:1005424617101.

    Article  CAS  PubMed  Google Scholar 

  28. Brzozowski T, Konturek PC, Pajdo R, et al. Importance of brain-gut axis in the gastroprotection induced by gastric and remote preconditioning. J Physiol Pharmacol. 2004;55:165–177.

    CAS  PubMed  Google Scholar 

  29. Lawson DC, Mantyh CR, Pappas TN. Effect of CGRP antagonist, alpha-CGRP 8–37, on acid secretion in the dog. Dig Dis Sci. 1994;39:1405–1408. doi:10.1007/BF02088041.

    Article  CAS  PubMed  Google Scholar 

  30. Manela FD, Ren J, Gao J, McGuigan JE, Harty RF. Calcitonin gene-related peptide modulates acid-mediated regulation of somatostatin and gastrin release from rat antrum. Gastroenterology. 1995;109:701–706. doi:10.1016/0016-5085(95)90376-3.

    Article  CAS  PubMed  Google Scholar 

  31. Asako H, Kubes P, Wallace J, Gaginella T, Wolf RE, Granger DN. Indomethacin-induced leukocyte adhesion in mesenteric venules: role of lipoxygenase products. Am J Physiol. 1992;262:G903–G908.

    CAS  PubMed  Google Scholar 

  32. Gambero A, Marostica M, Becker TL, Pedrazzoli Jr J. Effect of different cyclooxygenase inhibitors on gastric adaptive cytoprotection induced by 20% ethanol. Dig Dis Sci. 2007;52:425–433. doi:10.1007/s10620-006-9487-4.

    Article  CAS  PubMed  Google Scholar 

  33. Choi SM, Shin JH, Kang KK, Ahn BO, Yoo M. Gastroprotective effects of DA-6034, a new flavonoid derivative, in various gastric mucosal damage models. Dig Dis Sci. 2007;52:3075–3080. doi:10.1007/s10620-006-9657-4.

    Article  CAS  PubMed  Google Scholar 

  34. Fiorucci S, de Lima OM Jr, Mencarelli A, et al. Cyclooxygenase-2-derived lipoxin A4 increases gastric resistance to aspirin-induced damage. Gastroenterology. 2002;123:1598–1606. doi:10.1053/gast.2002.36558.

    Article  CAS  PubMed  Google Scholar 

  35. Souza MH, de Lima OM Jr, Zamuner SR, Fiorucci S, Wallace JL. Gastritis increases resistance to aspirin-induced mucosal injury via COX-2-mediated lipoxin synthesis. Am J Physiol Gastrointest Liver Physiol. 2003;285:G54–G61.

    CAS  PubMed  Google Scholar 

  36. Claria J, Serhan CN. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci USA. 1995;92:9475–9479. doi:10.1073/pnas.92.21.9475.

    Article  CAS  PubMed  Google Scholar 

  37. Gyires K, Hermecz I, Knoll J. The effect of some anti-ulcer agents on the early vascular injury of gastric mucosa induced by ethanol in rats. Acta Physiol Hung. 1989;73:149–154.

    CAS  PubMed  Google Scholar 

  38. Szabo S, Trier JS, Brown A, Schnoor J. Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology. 1985;88:228–236.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the grant no. 06-2007-134-0 from the Seoul National University Hospital Research Fund.

Author information

Authors and Affiliations

  1. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, South Korea

    Jung Mook Kang, Nayoung Kim, Ji Hyun Park, Mi Kyoung Lee, Joo Sung Kim, Hyun Chae Jung & In Sung Song

  2. Department of Internal Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, South Korea

    Nayoung Kim

  3. Life Science R&D Center, SK Chemicals, Suwon, Gyeonggi-do, South Korea

    Bongcheol Kim, Joo-Hyon Kim & Bong-Yong Lee

  4. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea

    Hye Seung Lee

  5. Department of Pharmacology, Seoul National University College of Medicine, Seoul, South Korea

    In-Jin Jang

Authors
  1. Jung Mook Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nayoung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bongcheol Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joo-Hyon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bong-Yong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ji Hyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mi Kyoung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hye Seung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. In-Jin Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Joo Sung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hyun Chae Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. In Sung Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nayoung Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kang, J.M., Kim, N., Kim, B. et al. Gastroprotective Action of Cochinchina Momordica Seed Extract Is Mediated by Activation of CGRP and Inhibition of cPLA2/5-LOX Pathway. Dig Dis Sci 54, 2549–2560 (2009). https://doi.org/10.1007/s10620-008-0671-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0671-6

Keywords

Search

Navigation