Nutritional Sciences

The Korean Nutrition Society (한국영양학회)
권호 표지

Inhibition of Red Ginseng on 5-Hydroxyeicosatetraenoic Acid (5-HETE) Biosynthesis from Arachidonic Acid in Helicobacter Pylori-infected Gastric Cells

  • Park Soo-Jin (Ginseng Research Group, Korea Food Research Institute)
  • Published : 2006.08.01
Download PDF
⟨ Previous Next ⟩

Abstract

Helicobacter pylori (H. pylori) infection rapidly stimulated either COX-2 or 5-LOX and released arachidonic acid metabolites that have been considered as pivotal mediators in H. pylori-induced inflammatory responses. To determine whether red ginseng extract (RGE) can suppress the biosynthesis of 5(S)-hydroxyeicosatetraenoic acids (HETE), a precursor metabolite of leukotrienes B4 (LTB4) in H. pylori-provoked inflammatory responses in gastric epithelial cells, the biosynthesis of monohydroxy fatty acids was measured using radioactive arachidonic acid and validated by RP-HPLC using non-radioactive AA as substrate in AGS cells cocultured with H. pylori (ATCC 43504) with or without pretreatment of RGE. Among three known major HETEs, H. pylori infection specifically induced the biosynthesis of $^{14}C-5(S)-HETE$ rather than the complex of $^{14}C-15S-/^{14}C-12(S)-HETE$ from $^{14}C-AA$, concomitantly obtained by HPLC(p<0.01). RGE, 1 to $100{\mu}g/ml$, selectively suppressed H. pylori-stimulated $^{14}C-5(S)-HETE$ production implying the attenuation of 5-lipoxygenase activity, of which was similar to known LOX inhibitor NDGA $(10{\mu}M)$ (p<0.01). However, the amount of 5(S)-HETE was significantly reduced by higher dose of RGE $(100{\mu}g/ml)$ (p<0.05). These results indicated that LOX pathway might be one of principle pathogenic mechanisms of H. pylori and red ginseng could be a nutraceutical against H. pylori infection through inhibiting action of LOX activity.

Keywords

References

  1. Kikuchi S. Epidemiology of Helicobaeter pylori and gastric cancer. Gastric Cancer 5:6-15, 2000 https://doi.org/10.1007/s101200200001
  2. International Agency for Research on cancer. Schistosomes liver flukes and Helicobacter pylori. Monograph, pp.61, Lyon, 1994
  3. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pyloriinfection and the development of gastric cancer. N Engl J Med 345:784-789, 2001 https://doi.org/10.1056/NEJMoa001999
  4. Hahm KB, Kim DH, Lee KM, Lee JS, Surh YJ, Kim YB, Yoo BM, Kim JH, Joo HJ, Cho YK, Nam KT, Cho SW. Effect of long-term administration of rebamipide on Helicobacter pylori infection in mice. Aliment Pharmacol Ther 18:S24-38, 2003 https://doi.org/10.1046/j.1365-2036.18.s1.3.x
  5. Israel DA, Peek RM. Pathogenesis of Helicobacter pylori-induced gastric inflammation. Aliment Pharmacol Ther 15:1271-1290, 2001 https://doi.org/10.1046/j.1365-2036.2001.01052.x
  6. Nakaya A, Wakabayashi H, Imamura L, Fukuta K, Makimoto S, Naganuma K, Orihara T, Minemura M, Shimizu Y, Nagasawa T, Hamazaki T, Watanabe A. Helicobacter pylori alters n-6 fatty acid metabolism and prostaglandin $E_2$ synthesis in rat gastric mucosal cells. J Gastroenterol Hepatol 16:1197-1205, 2001 https://doi.org/10.1046/j.1440-1746.2001.02541.x
  7. Wakabayashi H, Orihara T, Nakaya A, Miyamoto A, Watanabe A. Effect of Helicobacter pylori infection on gastric mucosal phospholipid contents and their fatty acid composition. J Gastroenterol Hepatol 13(6):566-571, 1998 https://doi.org/10.1111/j.1440-1746.1998.tb00691.x
  8. Orihara T, Wakabayashi H, Nakaya A, Fukuta K, Makimoto S, Naganuma K, Entani A, Watanabe A. Effect of Helicobacter pylori eradication on gastric mucosal phospholipid content and its fatty acid composition. J Gastroenterol Hepatol 16(3):269-75, 2001 https://doi.org/10.1046/j.1440-1746.2001.02440.x
  9. Marlink KL, Bacon KD, Sheppard BC, Ashktorab H, Smoot DT, Cover TL, Deveney CW, Rutten MJ. Effects of Helicobacter pylori on intracellular $Ca^{2+}$ signaling in normal human gastric mucous epithelial cells. Am J Physiol Gastrointest Liver Physiol 285(1): 163-176, 2003 https://doi.org/10.1152/ajpgi.00257.2002
  10. Nardone G, Holicky EL, Uhl JR, Sabatino L, Staibano S, Rocco A, Colantuoni V, Manzo BA, Romano M, Budillon G, Cockerill FR 3rd, Miller LJ. In vivo and in vitro studies of cytosolic phospholipase $A_2$ expression in Helicobacter pylori infection. Infect Immun 69(9):5857-5863, 2001 https://doi.org/10.1128/IAI.69.9.5857-5863.2001
  11. Pomorski T, Meyer TF, Naumann M. Helicobacter pyloriinduced prostaglandin $E_2$ synthesis involves activation of cytosolic phospholipase $A_2$ in epithelial cells. J Biol Chem 276(1):804-810, 2001 https://doi.org/10.1074/jbc.M003819200
  12. Steinberg G, Slaton WH Jr, Howton DR, Mead JF. Metabolism of essential fatty acids. Incorporation of linoleate into arachidonic acid. J Biol Chem 220(1):257-264, 1956
  13. Scheiman JM, Greenson JK, Lee J, Cryer B. Effect of cyclooxygenase-2 inhibition on human Helicobacter pylori gastritis: mechanisms underlying gastrointestinal safety and implications for cancer chemoprevention. Aliment Pharmacol Ther 17(12):1535-1543, 2003 https://doi.org/10.1046/j.1365-2036.2003.01587.x
  14. Nam KT, Hahm KB, Oh SY, Yeo M, Han SU, Ahn B, Kim YB, Kang JS, Jang DD, Yang KH, Kim DY. The selective cyclooxygenase-2 inhibitor nimesulide prevents Helicobacter pylori-associated gastric cancer development in a mouse model. Clin Cancer Res 10(23):8105-13, 2004 https://doi.org/10.1158/1078-0432.CCR-04-0896
  15. Etienne A, Soulard C, Touvay C, Clostre F, Braquet P. In vivo anti-allergic and anti-inflammatory effects of drugs that inhibit lipoxygenase activity in vitro. Int J Tissue React 7(6):459-62, 1985
  16. Meier RW, Niklaus G, Dewald B, Fey MF, Tobler A. Inhibition of the arachidonic acid pathway prevents induction of IL-8 mRNA by phorbol ester and changes the release of IL-8 from HL 60 cells: differential inhibition of induced expression of IL-8, TNF-alpha, IL-1 alpha, and IL-1 beta. J Cell Physiol 165(1):62-70, 1995 https://doi.org/10.1002/jcp.1041650108
  17. Denizot Y, Godard A, Raher S, Trimoreau F, Praloran V. Lipid mediators modulate the synthesis of interleukin 8 by human bone marrow stromal cells. Cytokine 11(8):606-610, 1999 https://doi.org/10.1006/cyto.1998.0467
  18. Sharma SA, Tummuru MK, Blaser MJ, Kerr LD. Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor-kappa B in gastric epithelial cells. J Immunol 160:2401-2407, 1998
  19. Schroder JM. The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate5-lipoxygenase, but not the release of cellular arachidonate. J Exp Med 170(3):847-863, 1989 https://doi.org/10.1084/jem.170.3.847
  20. Aoki Y, Qiu D, Zhao GH, Kao PN. Leukotriene B4 mediates histamine induction of NF-kappaB and IL-8 in human bronchial epithelial cells. Am J Physio 1274:L1030-1039, 1998
  21. Teng CM, Kuo SC, Ko FN, Lee JC, Lee LG, Chen SC, Huang TF. Antiplatelet actions of panaxynol and ginsenosides isolated from ginseng. Biochim Biophys Acta 990(3):315-320, 1989 https://doi.org/10.1016/S0304-4165(89)80051-0
  22. Park HJ, Rhee MH, Park KM, Nam KY, Park KH. Effect of non-saponin from Panax ginseng on cGMP and thromboxane A2 in human platelet aggregation. J Ethnopharmco 149: 157-162, 1995
  23. Park EK, Choo MK, HanMJ, Kim DH. Ginsenoside Rhl possesses antiallergic and anti-inflammatory activities. Int Arch Allergy Immunol 133(2): 113-120, 2004 https://doi.org/10.1159/000076383
  24. Keum YS, Han SS, Chun KS, Park KK, Park JH, Lee SK, Surh YJ, Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutat Res 523(4):75-85, 2003 https://doi.org/10.1016/S0027-5107(02)00323-8
  25. Park S, Choue RW, Cho Y, Ziboh VA. Regional biosynthesis of prostaglandins and hydroxyeicosatetraenoic acids from arachidonic acid in the rat stomach tissue. Prostaglandins Leukot Essent Fatty Acids 68(1):35-42, 2003 https://doi.org/10.1016/S0952-3278(02)00233-8
  26. Wescott JY, Balazy M, Stenmark KR, Murphy RC. Analysis of leukotriene D4 in human lung lavage by HPLC, RIA and mass spectrometry. Adv Prostaglandin Thromboxane Leukot Res 16:353-361, 1986
  27. Park S, Won YM, Cho JS, Jin JH, Hahm KB. Rescue of Helicobacter pylori induced Cytotoxicity by Red Ginseng. Dig Dis Sci 50(7):1218-1227; 2004 https://doi.org/10.1007/s10620-005-2763-x
  28. Nam KT, Hahm KB, Oh SY, Yeo M, Han SU, Ahn B, Kim YB, Kang JS, Jang DD, Yang KH, Kim DY. The selective cyclooxygenase-2 inhibitor nimesulide prevents Helicobacter pylori-associated gastric cancer development in a mouse model. Clin Cancer Res 10(23):8105-8113, 2004 https://doi.org/10.1158/1078-0432.CCR-04-0896
  29. Choi HJ, Han HS, Park JH, Son JH, Pae JH, Choi C. PLA2 inhibiting, Anticancer effect of polyphenol rich fractions from Panax Ginseng C. A. Meyer. J Korean Soc Agric Chem Biotechnol 46(3):251-6, 2003
  30. Kimura S, Fukuda T, Arakawa T, Kobayashi K. Leukotriene levels of Helicobacter pylori-infected gastric mucosa. Nippon Rinsho 51(12):3159-3162, 1993
  31. Marleau S, Fruteau de Laclos B, Sanchez AB, Poubelle PE, BoRGat P. Role of 5-lipoxygenase products in the local accumulation of neutrophils in dermal inflammation in the rabbit. J lmmunol 163(6):3449-3458, 1999
  32. Konturek JW, Bielanski W, Konturek SJ, Domschke W. Eradication of Helicobacter pylori and gastrin-somatostatin link in duodenal ulcer patients. J Physiol Pharmacol 47(1) :161-175, 1996
  33. Ghosh J. Inhibition of arachidonate 5-lipoxygenase triggers prostate cancer cell death through rapid activation of c-jun N-terminal kinase. Biochem Biophys Res Commun 307:342-349, 2003 https://doi.org/10.1016/S0006-291X(03)01201-4
  34. Tseng HJ, Chan CC, Chan EC. Sphingomyelinase of Helicobacter pylori-induced cytotoxicity in AGS gastric epithelial cells via activation of JNK kinase. Biochem Biophys Res Commun 314(2):513-518, 2004 https://doi.org/10.1016/j.bbrc.2003.12.125
  35. Shimakura S, Boland CR. Eicosanoid production by the human gastric cancer cell line AGS and its relation to cell growth. Cancer Res 52(7): 1744-1749, 1992
  36. Foryst-Ludwig A, Neumann M, Schneider-Brachert W, Neumann M Curcumin blocks $NF{\kappa}B$ and the motogenic respinse in infected epithelial cells. Biochem Biophys Res Commun 316:1065-1072, 2004 https://doi.org/10.1016/j.bbrc.2004.02.158
  37. Di Carlo G, Mascolo N, Izzo AA, Capasso F. Flavonoids; old and new aspects of a class of natural therapeutic drugs. Life Sci 65:337-53, 1999 https://doi.org/10.1016/S0024-3205(99)00120-4
  38. Wallace JM. Nutritional and botanical modulation of the inflammatory cascade-eicosanoids, cyclooxygenases, and lipoxygenases-as an adjunct in cancer therapy. Integr Cancer Ther 1(1):7-37, 2002
  39. Lee KM, Yeo M, Choue JS, Jin JH, Park SJ, Cheong JY, Lee KJ, Kim JH, Hahm KB. Protective mechanism of epigallocatechin-3-gallate against Helicobacter pylori-induced gastric epithelial cytotoxicity via the blockage of TLR-4 signaling. Helicobacter 9(6):632-642, 2004 https://doi.org/10.1111/j.1083-4389.2004.00281.x
  40. Kim YK, Guo Q, Packer L. Free radical scavenging activity of Red Ginseng aqueous extracts. Toxicology 172(2): 149-156, 2002 https://doi.org/10.1016/S0300-483X(01)00585-6
  41. Lee JH, Park EK, Uhm CS, Chung MS, Kim KH. Inhibition of Helicobacter pylori adhesion to human gastric adenocarcinoma epithelial cells by acidic polysaccharides from Artemisia capillaris and Panax ginseng. Planta Med 70(7):615-619, 2004 https://doi.org/10.1055/s-2004-827183
  42. Bae EA, Han MJ, Baek NI, Kim DH. In vitro anti-Helicobacter pylori activity of panaxytriol isolate from ginseng. Arch Pharm Res 24:297-299, 2001 https://doi.org/10.1007/BF02975095
  43. Smolinski AT, Pestka JJ. Modulation of lipopolysaccharide-induced proinflammatory cytokine production in vitro and in vivo by the herbal constituents apigenin (chamomile), ginsenoside Rb (1) (ginseng) and parthenolide (feverfew). Food Chem Toxicol 41:1381-1390, 2003 https://doi.org/10.1016/S0278-6915(03)00146-7
  44. Hong J, Bose M, Ju J, Ryu JH, Chen X, Sang S, Lee MJ, Yang CS. Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase $A_2$, cyclooxygenases and 5-lipoxygenase. Carcinogenesis 25(9):1671-169, 2004 https://doi.org/10.1093/carcin/bgh165