Effects of Grape Extracts on Free Radical Scavenging Activity and Inhibition of Pro-Inflammatory Mediator Production in Mouse Macrophage Cells

포도 추출물들의 자유 라디칼 소거 작용 마우스 대식세포주의 염증 발현 매개 인자들에 대한 생성 억제 효과

  • Published : 2003.02.01


Antioxidant and anti-inflammatory potentials of various grape extracts were evaluated. Extracts from Kyho seed, Kyho stem, and Campbell seed showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities compared to resveratrol $(IC_{50}=16.9,\;21.5,\;21.9,\;34.6\;{\mu}g/mL,\;respectively)$, among which, antioxidant effect of Kyho seed extract were similar to that of vitamin C $(IC_{50}=12.2\;{\mu}g/mL)$. These extracts also exhibited inhibitory activities on lipopolysaccharide (LPS)-induced prostaglandin $E_2$ production and nitrite formation in mouse macrophage RAW 264.7 cells at $50\;{\mu}g/mL$. Kyho stem and seed extracts showed growth inhibitory activities in human lung and colon cancer cells. These results suggest the potential roles of grape extracts as antioxidants and anti-inflammatory agents.


grape extracts;free radical scavenging;prostaglandins;iNOS;mouse macrophage cells


  1. Lander, H.M. An essential role for free radicals and derived species in signal transduction. FASEB J. 11: 118-124 (1997)
  2. Fremont, L. Biological effects of resveratrol. Life Sci. 66: 663-673 (2000) https://doi.org/10.1016/S0024-3205(99)00410-5
  3. Bhat, K.P.L. and Pezzuto, J.M. Cancer chemopreventive activity ofresveratrol. Ann. N. Y. Acad. Sci. 957: 210-229 (2002) https://doi.org/10.1111/j.1749-6632.2002.tb02918.x
  4. Ferguson, L.R. Role of plant polyphenols in genomic stability. Mutat. Res. 475: 89-111 (2001) https://doi.org/10.1016/S0027-5107(01)00073-2
  5. Sheng, H., Shao, J., Morrow, J.D., Beachamp, R.D. and Dubois, R.N. Modulation of apotosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res. 58: 362-366 (1998)
  6. Kroncke, K.D., Fehsel, K. and Kolb-Bachofen, V. Inducible nitric oxide synthase in human diseases. Clin. Exp. Immunol. 113: 147-156 (1998) https://doi.org/10.1046/j.1365-2249.1998.00648.x
  7. Dreher, D. and Junod, A.F. Role of oxygen free radicals in cancer development. Eur. J. Cancer 32A: 30-38 (1998)
  8. Dannenberg, A.J., Altorki, N.K., Boyle, J.O., Dang, C., Howe, L.R., Weksler, B.B. and Subbaramaiah, K. Cyclo-oxygenase-2: a pharmacological target for the prevention of cancer. Lancet Oncol. 2: 544-551 (2001) https://doi.org/10.1016/S1470-2045(01)00488-0
  9. Lee, S.K., Mbwambo, Z.H., Chung, H., Luyengi, L., Gamez, E.J.C., Metha, R.G., Kinghorn, A.D. and Pezzuto, J.M. Evaluation of the antioxidant potential of natural products. Comb. Chem. High Through Screening 1: 35-46 (1998)
  10. Ames, B.N., Shigenaga, M.K. and Hagen, T.M. Oxidants, antioxidants, and the degenerative disease of aging. Proc. Natl. Sci. USA 90: 7915-7922 (1993) https://doi.org/10.1073/pnas.90.17.7915
  11. Frankel, E.N., Kanner, J., German, J.B., Parks, E. and Kinsella, J.E. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 341: 454-457 (1993) https://doi.org/10.1016/0140-6736(93)90206-V
  12. Tsujii, M., Kawano S., Tsujii, S., Sawaoka, H., Hori, M. and Dubois, R.N. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93: 705-716 (1998) https://doi.org/10.1016/S0092-8674(00)81433-6
  13. Dubois, R.N., Abramson, S.B., Crofford, L., Gupta, R.A., Simon, L.S., Van De Putte, L.B. and Lipsky, P.E. Cyclooxygenase in biology and disease. FASEB J. 12: 1063-1073 (1998)
  14. Oshima, H. and Bartsch, H. Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat. Res. 305: 253-264 (1994) https://doi.org/10.1016/0027-5107(94)90245-3
  15. Kelloff, G.J., Crowell, J.A., Steele, V.E., Lubet, R.E., Malone, W.A., Boone, C.W., Kopelovich, L., Hawk, E.T., Lieberman, R., Lawrence, J.A., Ali, I., Viner, J.L. and Sigman, C.C. Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. J. Nutr. 130: 467S-471S (2000)
  16. Patel, R.P., Moelliring, D., Murphy-Ullrich, J., Jo, H., Beckman, J.S. and Darley-Usmar, V.M. Cell signaling by reactive nitrogen and oxygen species in atherosclerosis. Free Radic. Biol. Med. 28: 1780-1794 (2000) https://doi.org/10.1016/S0891-5849(00)00235-5
  17. Stuehr, D.J. Mammalian nitric oxide synthase. Biochim. Biophys. Acta. 1411: 217-230 (1999) https://doi.org/10.1016/S0005-2728(99)00016-X
  18. Martinez, J. and Moreno, J.J. Effect of resveratrol, a natural po1yphenolic compound, on reactive oxygen species and prostaglandin production. Biochem. Pharmacol. 59: 865-870 (2000) https://doi.org/10.1016/S0006-2952(99)00380-9
  19. Briviba, K., Pan, L. and Rechkemmaer, G. Red wine polyphenols inhibit the growth of colon cancer cells and modulate the activation pattern of mitogen-activated protein kinases. J. Nutr. 132: 2814-8 (2002)
  20. Halliwell, B., Gutteridge, J.M.C. and Cross, C.E. Free radicals, antioxidants, and human disease: Where are we now? J. Lab. Clin. Med. 119: 598-620 (1992)
  21. Herschman, H.R. Prostaglandin synthase 2. Biochim. Biophys. Acta. 1299: 125-40 (1999)
  22. Joe, A.K., Liu, H., Suzui, M., Vural, M.E., Xiao, D. and Weinstein, I.B., Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin. Cancer Res. 8: 893-903 (2002)