Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOS and COX-2 in RAW264.7 cells

Abstract

Both reactive oxygen- and nitrogen-derived reactive species play important roles in physiological and pathophysiological conditions. Flavones, luteolin and luteolin-7-O-glucoside along with a rich plant source of both flavones, namely dandelion (Taraxacum officinale) flower extract were studied for antioxidant activity in different in vitro model systems. In this current study, luteolin and luteolin-7-O-glucoside at concentrations lower than 20 μM, significantly (p < 0.05) suppressed the productions of nitric oxide and prostaglandin E2 (PGE2) in bacterial lipopolysaccharide activated-mouse macrophage RAW264.7 cells without introducing cytotoxicity. The inhibitory effects were further attributed to the suppression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression, and not reduced enzymatic activity. Similar suppression for both inducible enzymes was also found with the presence of dandelion flower extract, specifically, the ethyl acetate fraction of dandelion flower extract which contained 10% luteolin and luteolin-7-O-glucoside.

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

References

  1. 1.

    Darley-Usmar V, Wiseman H, Halliwell B: Nitric oxide and oxygen radicals: A question of balance. FEBS Lett 369: 131–135, 1995

    Google Scholar 

  2. 2.

    Ischiropoulos H, Zhu L, Beckman JS: Peroxynitrite formation from macrophage-derived nitric oxide. Arch Biochem Biophys 298: 446–451, 1992

    Google Scholar 

  3. 3.

    MacMicking J, Xie QW, Nathna C: Nitric oxide and macrophage func-tion. Annu Rev Immunol 15: 323–350, 1997

    Google Scholar 

  4. 4.

    Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS: Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: Down-regulation of COX-2 and iNOS through suppression of NF-ê B activation. Mutat Res 480: 243–268, 2001

    Google Scholar 

  5. 5.

    Chen YC, Shen SC, Lee WR, Hou WC, Yang LL, Lee TJF: Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced NOS and cycloxygenase-2 gene expression by rutin, quercetin and quercetin pentaacetate in RAW264.7 macrophages. J Cell Biochem 82: 537–548, 2001

    Google Scholar 

  6. 6.

    Bremner P, Heinrich M: Natural products as targeted modulator of nu-clear factor-ê B pathway. J Pharm Pharmacol 54: 453–472, 2002

    Google Scholar 

  7. 7.

    Chan MMY, Fong D, Ho CT, Huang HI: Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate. Biochem Pharmacol 54: 1281–1286, 1997

    Google Scholar 

  8. 8.

    Lin YL, Lin JK: (-)-epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-kappa B. Mol Pharmacol 52: 465–472, 1997

    Google Scholar 

  9. 9.

    Hu C, Kitts DD: Antioxidant, prooxidant and cytotoxic activities of solvent fractionated dandelion (Taraxacum officinale)flower extracts in vitro.JAgric Food Chem 52: 301–310, 2003

    Google Scholar 

  10. 10.

    Wang J, Mazza G: Inhibitory effects of anthocyanins and other phenolic compounds on nitric oxide production in LPS/INF-gamma-activated RAW264.7 macrophage. J Agric Food Chem 50: 850–857, 2002

    Google Scholar 

  11. 11.

    Chen YC, Shen SC, Chen LG, Lee TJF, Yang LL: Wogonin, baicalin and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions by nitric oxide synthase and lipopolysaccharide. Biochem Pharmacol 61: 1417–1427, 2001

    Google Scholar 

  12. 12.

    Heim KE, Tagliaferro AR, Bobilya D: Flavonoid antioxidants: Chem-istry, metabolism and structure-activity relationships. J Nutr Biochem 10: 572–584, 2002

    Google Scholar 

  13. 13.

    Scalbert A, Williamson G: Dietary intake and bioavailability of polyphe-nols. J Nutr 130: 2073S–2085S, 2002

    Google Scholar 

  14. 14.

    Sampson L, Rimm E, Hollman PC, de Vries JH, Katan MB: Flavonol and flavone intakes in US health professionals. J Am Diet Assoc 102: 1414–1420, 2002.

    Google Scholar 

  15. 15.

    Cho SY, Park JY, Park EM, Choi MS, Lee MK, Jeon SM, Jan MK, Kim MJ, Park YB: Alternation of hepatic antioxidant enzyme activities and lipid profile in streptozotocin-induced diabetic rats by supplementation of dandelion water extract. Clin Chim Acta 317: 109–117, 2002

    Google Scholar 

  16. 16.

    Shimoi K, Okada H, Furugori M, Goda T, Takase S, Suzuki M, Hara Y, Yamamoto H, Kinae N: Intestinal absorption of luteolin and luteolin-7-O-beta-glucoside in rats and humans. FEBS Lett 438: 220–224, 1998

    Google Scholar 

  17. 17.

    Hu C, Zawistowski J, Ling W, Kitts DD: Black rice extract (Oryza sativa L. indica) suppresses both reactive oxygen species and nitric oxide in both chemical and biological models. J Agric Food Chem 51: 5271–5277, 2003

    Google Scholar 

  18. 18.

    Liang YC, Huang YT, Tsai SH, Lin-Shiau SY, Chen CF, Lin JK: Sup-pression of inducible cycooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogen-sis 20: 1945–1952, 1999

    Google Scholar 

  19. 19.

    Bollag DM, Rozycki MD, Edelstein SJ: Immunoblotting. In: Protein Methods 2nd edn. Willey-Liss Publication, 1996, pp 195–227

  20. 20.

    Shimpo M, Ikeda U, Maeda Y, Ohya K, Murakami Y, Shimada K: Effect of aspirin-like drugs on nitric oxide synthesis in rat vascular smooth muscle cells. Hypertension 35: 1085–1091, 2000

    Google Scholar 

  21. 21.

    Dearden JC: Partition and lipophilicity in quantitative structure-activity relationships. Environ Health Perspect 61: 203–228, 1985

    Google Scholar 

  22. 22.

    Hirobe C, Qiao ZS, Takeya K, Itokawa H: Cytotoxic flavonoids from Vitex agnus-castus.Phytochemistry 46: 521–524, 1997

    Google Scholar 

  23. 23.

    Galvez M, Martin-Cordero C, Lopez-Lazaro M, Cortes F, Ayuso MJ: Cytotoxic effect of Plantago spp. on cancer cell lines. J Ethnopharmacol 88: 125–130, 2003

    Google Scholar 

  24. 24.

    Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP: Effects of naturally oc-curring flavonoids on nitric oxide production in the macrophage cell line RAW264.7 and their structure-activity relationships. Biochem Pharma-col 58: 759–765, 1999

    Google Scholar 

  25. 25.

    O'Connell MA, Bennett BL, Mercurio F, Manning AM, Mackman N: Role of IKK1and IKK2in lipopolysaccharide signaling in human mono-cytic cells. J Biol Chem 273: 30410–30414, 1998

    Google Scholar 

  26. 26.

    Sheu F, Lai HH, Yen GC: Suppression effect of soy isoflavones on nitric oxide production in RAW264.7 macrophages. J Agric Food Chem 49: 1767–1772, 2001

    Google Scholar 

  27. 27.

    Xagorari A, Papapetropoulos A, Mauromatis A, Economou M, Fotsis T, Roussos C: Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophage. J Pharm Exp Ther 296: 181–187, 2001

    Google Scholar 

  28. 28.

    Wadsworth TL, Koop DR: Effects of Ginkgo biloba extract (EGb761) and quercetin on lipopolysaccharide-induced release of nitric oxide. Chem Biol Interact 137: 43–58, 2001

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hu, C., Kitts, D.D. Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOS and COX-2 in RAW264.7 cells. Mol Cell Biochem 265, 107–113 (2004). https://doi.org/10.1023/B:MCBI.0000044364.73144.fe

Download citation

  • luteolin
  • luteolin-7-O-glucoside
  • dandelion
  • iNOS
  • COX-2