Effects of Kimchi Extracts on Production of Nitric Oxide by Activated Macrophages, Transforming Growth Factor $\beta$1 of Tumor Cells and Interleukin-6 in Splenocytes

  • Kim, Kwang-Hyuk (Dept. of Microbiology, Kosin Medical College) ;
  • Kim, So-Hee (School of Food Science, and Institute of Environment and Health, Dong-Ju College) ;
  • Park, Kun-Young (Dept. of Food Science and nutrition, and Kimchi Research Institute, Pusan National University)
  • Published : 2001.06.01


Methanol extracts form four kinds of kimchi, which were differently prepared in kinds and levels of sub-ingredients, were given to Balb/c mice for 3 weeks (0.5 mg/kg/day). Peritoneal macrophages isolated from mice treated with kimchi extracts and saline were stimulated by lipopolysaccharide (LPS). K3 and K4 kimchis, containing more red pepper powder, garlic, Chinese pepper powder, mustard leaf and organically cultivated Korean cabbage, significantly increased NO production by the activated macrophages (p<0.05). K1, K2, K3 and K4 kimchi extracts (0.01, 0.1, 1.0 $\mu\textrm{g}$) significantly reduced the increased TGF-$\beta$1 production of H.pylori lysate (0.01 $\mu\textrm{g}$)-activated human epithelial RPMI 2650 cells (5$\times$10$^{4}$ cells/mL) at 24 and 48 hrs of treatment (p<0.01). However, the decreased TGF-$\beta$1 $\alpha$ production of RPMI 2650 cells by H. pylori lysate increased by treatment with kimchi extract for 72 hrs. Especially, K4 kimchi (containing organically cultivated Korean cabbage and more ingredients, modulated TGF-$\beta$1 production of H. pylori lysate-activated RPMI 2650 cells to the normal level (control) by treatment for 48 hrs. The treatment of K1 and K4 kimchi enhanced the LPS (0.01 $\mu\textrm{g}$/mL)-induced IL-6 production of splenocytes. The results suggest that kimchi might have an beneficial effect on cancer prevention due in part to the function enhancing NO production of activated macrophages. Our data suggest that kimchi could modulate TGF-$\beta$1 production by cancer cells and IL-6 production of splenocytes, thereby possibly contributing to control carcinogenesis and the immune system.


  1. J. Korean Soc. Food Nutr. v.24 The nutritional evaluation, and antimutagenic and anticancer effects of kimchi Park. K.Y.
  2. The standardization of kimchi Park, W.S.;Gu, Y.J.;An, B.H.;Choi, S.Y.
  3. Criti. Rev. Food Sci. Nutr. v.34 Biological, microbiological and nutritional aspects of kimchi (Korean fermented vegetable products) Cheigh, H.S.;Park, K.Y.
  4. Symposium Presentation Reports of korean Soc. of Food Sience & Technology Nutritional evalution of kimchi Oh, Y.J.;Hwang, I.J.;Claus, L.
  5. Scientific technology of kimchi Gu, Y.J.;Choi, S.Y.
  6. Pure Appl. Chem. v.57 Carotenoids and cancer prevention experimental and epidemiological studies Mathew-Roth, M.M.
  7. Environ. Muta. Carcino. v.8 Effect of L=ascorbic acid of the mutagenicity of aflatoxin B₁ in the Salmonaella assay system Park, K.Y.;Kweon, M.H.;Baik, H.S.;Cheigh, H.S.
  8. Oncology v.10 Vitamin C and cancer prevention Bright-See, E.
  9. Cancer v.58 Diet, nutrition and cancer -The role of fiber- Kritchevsky, D.
  10. J. Agric. Food Chem. v.40 Content of potentially anticarcinogenic flavonoids of 28 vegetables 9 fruits commonly consumed in the Netherlands Hertog, M.G.L.;Hollman, P.C.H.;Ketan, M.B.
  11. J. Korean Soc. Food Nutr. v.20 Inhibitory effects of aflatoxin B₁ mediated mutagenicity by red pepper powder in the Sallmonella assay system Kim, S.H.;Park, K.Y.;Suh, M.J.
  12. J. Korean Food Sci. Technol. v.23 Inhibition effects of garlic on the mutagenicity in Sallmonella assay system and on the growth of HT-29 human colon carcinoma cells Park. K.Y.;Kim, S.H.;Suh, M.J.;Chung, H.Y.
  13. J. Korean Asso. Cancer Prev. v.3 Antimutagenic activities of lactic acid bacteria isolated from kimchi Son, T.J.;Kim, S,H.;Park, K.Y.
  14. J. Food Sci. Nutr. v.3 Antimutagenic activities of cell wall and cytosol fractions of lactic acid bacteria isolated from kimchi Park, K.Y.;Kim, S.H.;Son, T.J.
  15. J. Food Prot. v.53 Anticarcinogenic and immunological properties of dietary Latobacilli Fernandes, C.F.;Shahani, K.M.
  16. Foods Biotech. v.4 Antimutagenic effect of kimchi Park, K.Y.;Baek, K.A.;Rhee, S.H.;Cheigh, H.S.
  17. J. Food Sci. Nutr. v.2 Inhibitory effects of kimchi extracts on carcinogen-induced cytotoxicity and transformation in C3H/10T1/2 cells Choi, M.W.;Kim, K.H.;kim, S.H.;Park, K.Y.
  18. J. Food Sci. Nutr. v.4 Inhibitory effects of kimchi extracts on the growth and DNA synthesis of human cancer cells Hur, Y.M.;Kim,S.H.;Park, K.Y.
  19. J. Food Sci. Nutr. v.5 Inhibition of tumor formation and changes in hapatic enzyme activities by kimchi extracts in sarcoma-180 cell transplanted mice Hur, Y.M.;Kim, S.H.;Choi, J.W.;Park, K.Y.
  20. Inflammation v.18 Decreased production of nitric oxide by human neutrophils during septic multiple organ dysfunction syndrome Carreras, M.C.;Catz, S.D.;Pargament, G.A.;Del Bosco, C.G.;Poderoso, J.J.
  21. J. Immuno. v.144 Macrophage killing of Leishmania paraite in vivo is mediated by nitric oxide from L-arginine Liew, F.Y.;Millott, S.;Parkinson, C.;Palmer, R.M.J.;Moncada, S.
  22. Cell v.64 Molecular themes in oncogenesis Bishop, J.M.
  23. Cell v.64 Growth factors in development, transformation and tumorigenesis Cross, M.;Dexter, T.M.
  24. Science v.254 Growth factors and cancer Aaronson, S.
  25. Proc. Natl. Acad. Sci. USA v.92 Mammary tumor suppression by transforming growth factor β1 transgene expression Pierce, D.F., Jr.;Gorska, A.E.;Chytil, A.;Meise, K.S.;Page, D.L.;Coffrey, R.J., Jr.;Moses, H.L.
  26. J. Immunol. Methods v.180 Lipopolysaccharide in concentrations above 40 ng/mL stimulates proliferation of the IL-6-dependent B9 cell line Pedersen, M.R.;Jensen, S.;Christensen, J.D.;Hansen, E.W.
  27. J. Immuno. v.141 Release of reactive nitrogen intermediates and reactive oxgen intermediates from mouse peritoneal macrophage : Comparison of activation cytokines and evidence for independent production Ding, A.H.;Nathan, C.F.;Stuehr, D.J.
  28. J. Exp. Med. v.169 Regulation of macrophage funtions by L-arginine Albina, J.E.;Caldwell, M.D.;Henry, W.L. Jr.;Mills, C.D.
  29. FEBS Lett. v.275 Induction of nitric oxide synthetase by cytokines in vascular smooth muscle cells Busse, R.;Mulsch, A.
  30. Am. J. Physiol. v.259 Interleukin-1 and endotoxin activate soluble guanylate cyclase in vascular smooth muscle Beasley, D.
  31. FASEB J. v.5 The effects of endotoxin on endothelium-derived relaxing factor and nitric oxide production in cultured aortic endothelial cells Wright, T.F.;Myers, P.R.;Adams, H.R.
  32. Proc. Natl. Acad. Sci. U.S.A. v.87 Glcocorticoids inhibit the expression of an inducible but not the constitutive nitric oxide synthetase in vascular endothelial cells Radomski, M.W.;Palmer, R.M.J.;Moncada, S.
  33. Science v.235 Macrophage cytotoxicity : role for L-argininedeiminase and iminonitrogen oxidation to nitrite Hibbs, J.B.;Taintor, Jr., R.R.;Vavrin, Z.
  34. Biochem. Biophys. Res. Comm. v.157 Nitric oxide : a cytotoxic activated macrophage effector molecule Hibbs, J.B.;Taintor, Jr., R.R.;Varin, Z.;Rachlin, E.M.
  35. Nature v.345 Ischaemic injury mediator Beckman, J.S.
  36. Cancer Res. v.53 Increased transforming growth factor β expression inhibit cell proliferation in vitro, yet increases tumorigenicity and tumor growth of Meth A sarcoma cells Chang, H.L.;Gillett, N.;Figari, I.;Lopez, A.R.;Palladino, M.A.;Derynck, R.
  37. Cancer Res. v.57 Constitutive expression of mature transformaing growth factor β1 on the liver accelarates hapalocarcinogenesis in transgenic mice Factor, V.M.;Kao, C.Y.;Rugiu, E.S.;Woitach, J.T.;Jensen, M.R.
  38. Cell v.86 TGF-β1 inhibits the formation of begin skin tumors but enhances progression to invasive spindle carcinomas in transgenic mice Cui, W.;Fowlis, D.J.;Bryson, S.;Duffie, E.;Ireland, H.;Balman, A.;Akhurst, R.J.
  39. Genes & Dev. v.10 TGF-β1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells Oft, M.;Peli, J.;Rudaz, C.;Schwarz, H.;Beug, H.;Reichmann, E.
  40. Proc. Natl. Acad. Sci. U.S.A. v.87 A highly immunogenic tumor transforming growth factor type β1 cDNA escapes immune surveillance Torre-Amione, G.;Beauchamp, R.D.;Koeppen, H.;Park, B.H.;Schreiber, H.;Moses, H.L.;Rowley, D.A.
  41. Biochem. J. v.265 Interleukin-6 and the acute phage response Heinrich, P.C.;Castell, J.V.;Andus, T.
  42. Infect. Immun. v.61 Tumor necrosis factor alpha, interleukin-1 α, interleukin-6, and prostaglandin E₂ production in murine peritoneal macrophages infacted with Ehrlichia risticii Heeckeren, A.M.;Rikihisa, Y.;Park, J.;Fertel, R.