Food Science and Biotechnology

, Volume 20, Issue 6, pp 1713–1719 | Cite as

Anti-inflammatory effect of grape seed may involve the induction of heme oxygenase-1 and suppression of nuclear factor-κB activation

  • Jeehye Sung
  • Younghwa Kim
  • Youngmin Choi
  • Hyeonmi Ham
  • Heon-Sang Jeong
  • Junsoo Lee
Research Article
First Online:
Received:
Revised:
Accepted:

Abstract

This study aimed to elucidate the antiinflammatory mechanism of grape-seed acetone extract (GSAE) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The GSAE at the highest concentration (500 μg/mL) significantly inhibited nitric oxide production by approximately 78% and suppressed inducible nitric oxide synthase protein expression by approximately 83% compared to LPS-stimulated cells. The GSAE also suppressed inhibitor κBα phosphorylation and nuclear factor-κB (NF-κB; p65) transcriptional activity and translocation to the nucleus. In addition, GSAE induced the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner, and that blocking HO-1 activity eliminated the inhibitory effects of the GSAE. The addition of carbon monoxide, a byproduct of heme degradation by HO-1, mimicked the inhibitory action of low concentrations of GSAE. These data suggest that GSAE carries out anti-inflammatory actions in macrophages through the induction of HO-1 and suppression of NF-κB activation.

Keywords

grape seed anti-inflammation nitric oxide heme oxygenase-1 nuclear factor-κB 
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References

  1. 1.
    Lin W, Wu RT, Wu T, Khor TO, Kong AN. Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway. Biochem. Pharmacol. 76: 967–973 (2008)CrossRefGoogle Scholar
  2. 2.
    Park JH, Oh S, Lim SS, Lee YS, Shin HK, Choe NH, Park JH, Kim JK. Induction of heme oxygenase-1 mediates the anti-inflammatory effects of the ethanol extract of Rubus coreanus in murine macrophages. Biochem. Bioph. Res. Co. 351: 146–152 (2006)CrossRefGoogle Scholar
  3. 3.
    Heiss E, Herhaus C, Klimok BH, Cerhanse C. Nuclear factor-κB is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J. Biol. Chem. 276: 32008–32015 (2001)CrossRefGoogle Scholar
  4. 4.
    Wu SJ, Liu PL, Ng LT. Tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic cells. Mol. Nutr. Food Res. 52: 921–929 (2008)CrossRefGoogle Scholar
  5. 5.
    Coleman JW. Nitric oxide in immunity and inflammation. Int. Immunopharmacol. 1: 1397–1406 (2001)CrossRefGoogle Scholar
  6. 6.
    Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 6: 3051–3064 (1992)Google Scholar
  7. 7.
    Nathan C, Xie QW. Nitric oxide synthases: Roles, tolls, and controls. Cell 78: 915–918 (1994)CrossRefGoogle Scholar
  8. 8.
    Xie QW, Kashiwabara Y, Nathan C. Role of transcriptional factor NFκB/Rel in induction of nitric oxide synthase. J. Biol. Chem. 269: 4705–4708 (1994)Google Scholar
  9. 9.
    Barnes PJ. Nuclear factor-κB. Int. J. Biochem. Cell B. 29: 867–870 (1997)CrossRefGoogle Scholar
  10. 10.
    Griseavage JM, Wilk S, Ignarro LJ. Inhibitors of the proteasome pathway interfere with induction of nitric oxide synthase in macrophages by blocking activation of transcription factor NF-κB. P. Natl. Acad. Sci. USA 93: 3308–3312 (1996)CrossRefGoogle Scholar
  11. 11.
    Pergola C, Rossi A, Dugo P, Cuzzocrea S, Sautebin L. Inhibition of nitric oxide biosynthesis by anthocyanin fraction of blackberry extract. Nitric Oxide-Biol. Ch. 15: 30–39 (2006)CrossRefGoogle Scholar
  12. 12.
    Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: From basic science to therapeutic applications. Physiol. Rev. 86: 583–650 (2006)CrossRefGoogle Scholar
  13. 13.
    Kim J, Cha YN, Surh YJ. A protective role of nuclear factorerythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutat. Res. 690: 12–23 (2010)CrossRefGoogle Scholar
  14. 14.
    Poss KD, Tonegawa S. Reduced stress defense in heme oxygenase 1-deficient cells. P. Natl. Acad. Sci. USA 94: 10925–10930 (1997)CrossRefGoogle Scholar
  15. 15.
    Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J. Clin. Invest. 103: 129–135 (1999)CrossRefGoogle Scholar
  16. 16.
    Nicoli MC, Anese M, Rouseff RL, Zehavi U. Distibution of bound and free polyphenolic acids in oranges (Citrus sinensis) and grape fruit (Citrus paradise). J. Sci. Food Agr. 57: 417–426 (1991)CrossRefGoogle Scholar
  17. 17.
    Terra X, Valls J, Vitrac X, Mérrillon JM, Arola L, Ardèvol A, Bladé C, Fernandez-Larrea J, Pujadas G, Salvadó J, Blay M. Grape-seed procyanidins act as anti-inflammatory agents in endotoxinstimulated RAW 264.7 macrophages by inhibiting NF κB signaling pathway. J. Agr. Food Chem. 55: 4357–4365 (2007)CrossRefGoogle Scholar
  18. 18.
    Chacón MR, Ceperuelo-Mallafré V, Maymó-Masip E, Mateo-sanz JM, Arola L, Guitiérrez C, Fernandez-Real JM, Ardèvol A, Simón I, Vendrell J. Grape-seed procyanidins modulate inflammation on human differentiated adipocytes in vitro. Cytokine 47: 137–142 (2009)CrossRefGoogle Scholar
  19. 19.
    Nath J, Powledge A. Modulation of human neutrophil inflammatory responses by nitric oxide: Studies in unprimed and LPS-primed cells. J. Leukocyte Biol. 62: 805–816 (1997)Google Scholar
  20. 20.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−Ct method. Methods 25: 402–408 (2001)CrossRefGoogle Scholar
  21. 21.
    Moon KY, Hahn BS, Lee J, Kim YS. A cell-based assay system for monitoring NF-κB activity in human HaCat transfectant cells. Anal. Biochem. 292: 17–21 (2001)CrossRefGoogle Scholar
  22. 22.
    Furusawa JI, Funakoshi-Tago M, Tago K, Mashino T, Inoue H, Sonoda Y, Kasahara T. Licochalcone A significantly suppresses LPS signaling pathway through the inhibition of NF-κB p65 phosphorylation at serine 276. Cell Signal. 21: 778–785 (2009)CrossRefGoogle Scholar
  23. 23.
    Diaz-Guerra MJ, Velasco M, Martin-Sanz P, Bosca L. Evidence for common mechanisms in the transcriptional control of type II nitric oxide synthase in isolated hepatocytes. Requirement of NF-κB activation after stimulation with bacterial cell wall products and phorbol esters. J. Biol. Chem. 291: 30114–30120 (1996)Google Scholar
  24. 24.
    Lin HY, Juan SH, Shen SC, Hsu FL, Chen YC. Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in RAW264.7 macrophages involves heme oxygenase-1. Biochem. Pharmacol. 66: 1821–1832 (2003)CrossRefGoogle Scholar
  25. 25.
    Bagchi D, Bagchi M, Stohs S, Ray SD, Sen CK, Preuss HG. Cellular protection with proanthocyanidins derived from grape seeds. Ann. NY Acad. Sci. 957: 260–270 (2002)CrossRefGoogle Scholar
  26. 26.
    Chen CY, Jang JH, Li MH, Surh YJ. Resveratrol upregulate heme oxygenase-1 expression via activation of NF-E2-related factor in PC12 cells. Biochem. Bioph. Res. Co. 331: 993–1000 (2005)CrossRefGoogle Scholar
  27. 27.
    Shah ZA, Li RC, Ahmad AS, Kensler TW, Yamamoto M, Biswal S, Dore S. The flavanol (-)-epicatechin prevents stroke damage through the Nrf/HO-1 pathway. J. Cereb. Blood F. Metab. 30: 1951–1961 (2010)CrossRefGoogle Scholar
  28. 28.
    Kim KM, Pae HO, Zhung M, Ha HY, Ha YA, Chai KY, Cheong YK, Kim JM, Chung HT. Involvement of anti-inflammatory heme oxygenase-1 in the inhibitory effect of curcumin on the expression of pro-inflammatory inducible nitric oxide synthase in RAW264.7 macrophages. Biomed. Pharmacother. 62: 630–636 (2008)CrossRefGoogle Scholar
  29. 29.
    Hu CM, Liu YH, Cheah KP, Li JS, Lam CS, Yu WY, Choy CS. Heme oxygenase-1 mediates the inhibitory actions of brazilin in RAW264.7 macrophages stimulated with lipopolysaccharide. J. Ethnopharmacol. 121: 79–85 (2009)CrossRefGoogle Scholar
  30. 30.
    Lin HY, Shen SC, Chen YC. Anti-inflammatory effect of heme oxygenase-1: Glycosylation and nitric oxide inhibition in macrophages. J. Cell. Physiol. 202: 579–590 (2005)CrossRefGoogle Scholar
  31. 31.
    Kim YH, Sung J, Sung M, Choi Y, Jeong HS, Lee J. Involvement of heme oxygenase-1 in the anti-inflammatory activity of Chrysanthemum boreale Makino extracts on the expression of inducible nitric oxide synthase in RAW264.7 macrophages. J. Ethnopharmacol. 131: 550–554 (2010)CrossRefGoogle Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Netherlands 2011

Authors and Affiliations

  • Jeehye Sung
    • 1
  • Younghwa Kim
    • 1
  • Youngmin Choi
    • 1
  • Hyeonmi Ham
    • 1
  • Heon-Sang Jeong
    • 1
  • Junsoo Lee
    • 1
  1. 1.Department of Food Science and TechnologyChungbuk National UniversityCheongju, ChungbukKorea

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