Skip to main content
Log in

Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids

  • Inflammation and Immunomodulation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

A group of flavonoids isolated from medicinal plants and which are selective inhibitors of lipoxygenase activityin vitro: sideritoflavone, cirsiliol, hypolaetin-8-O-β-d-glucoside, hypolaetin, oroxindin, quercetagetin-7-O-β-d-glucoside, gossypin, hibifolin and gossypetin, besides leucocyanidol, have been studied for their effects on acute responses induced by carrageenin in mice. The oral administration of flavonoids to mice inhibited dose-dependently the development of paw oedema at 1, 3 and 5 h after carrageenin injection. A similar administration of flavonoids induced a dose-dependent inhibition of leukocyte accumulation in inflammatory exudates following intraperitoneal injection of carrageenin into mice. Some of the flavonoids exhibited a potency against leukocyte infiltration similar to that seen for inhibition of carrageenin oedema at 3 h of induction. In agreement with data reported in rats, indomethacin was much more effective on inhibition of prostaglandin E2 (PGE2) formation than on leukocyte infiltration in mice. The selectivity of flavonoids towards lipoxygenase is not retainedin vivo since they behave as dual inhibitors of PGE2 and leukotriene B4 (LTB4) formation in peritoneal exudates. Our data support the inhibition of arachidonic acid metabolism as one of the mechanisms by which flavonoids exert their anti-inflammatory effects.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. B. Havsteen,Flavonoids, a class of natural products of high pharmacological potency. Biochem. Pharmacol.32, 1141–1148 (1983).

    Article  PubMed  Google Scholar 

  2. M. J. Alcaraz and M. L. Ferrándiz,Modification of arachidonic metabolism by flavonoids. J. Ethnopharmacol.21, 209–229 (1987).

    Article  PubMed  Google Scholar 

  3. M. J. Alcaraz and M. J. Jiménez,Flavonoids as anti-inflammatory agents. Fitoterapia59, 25–38 (1988).

    Google Scholar 

  4. A. Villar, M. A. Gascó and M. J. Alcaraz,Anti-inflammatory and anti-ulcer properties of hypolaetin-8-glucoside, a novel plant flavonoid. J. Pharm. Pharmacol.36, 820–823 (1984).

    PubMed  Google Scholar 

  5. M. J. Jiménez, M. J. Alcaraz, M. L. Ferrándiz and A. Villar,Anti-inflammatory activity of a flavone from Sideritis leucantha. Planta Med.52, 541 (1986).

    Google Scholar 

  6. T. Yoshimoto, M. Furukawa, S. Yamamoto, T. Horie and S. Watanabe-Kohno,Flavonoids: potent inhibitors of arachidonate-5-lipoxygenase. Biochem. Biophys. Res. Commun.116, 612–618 (1983).

    PubMed  Google Scholar 

  7. M. J. Alcaraz and J. R. S. Hoult,Actions of flavonoids and the novel anti-inflammatory flavone, hypolaetin-8-glucoside, on prostaglandin biosynthesis and inactivation. Biochem. Pharmacol.34, 2477–2482 (1985).

    Article  PubMed  Google Scholar 

  8. M. A. Moroney, M. J. Alcaraz, R. A. Forder, F. Carey and J. R. S. Hoult,Selectivity of neutrophil 5-lipoxygenase and cyclo-oxygenase inhibition by an anti-inflammatory flavonoid glycoside and related aglycone flavonoids. J. Pharm. Pharmacol.40, 787–792 (1988).

    PubMed  Google Scholar 

  9. M. L. Ferrándiz, A. G. Ramachandran Nair and M. J. Alcaraz,Inhibition of sheep platelets arachidonate metabolism by flavonoids from Spanish and Indian medicinal herbs. Pharmazie45, 206–208 (1990).

    PubMed  Google Scholar 

  10. E. Sugishita, S. Amagaya and Y. Ogihara,Anti-inflammatory testing methods: comparative evaluation of mice and rats. J. Pharm. Dyn.4, 565–575 (1981).

    Google Scholar 

  11. D. E. Griswold, P. J. Marshall, E. F. Webb, R. Godfrey, J. Newton Jr., M. J. Di Martino, H. M. Sarau, J. G. Gleason, G. Poste and N. Hanna,SK&F 86002: a structurally novel anti-inflammatory agent that inhibits lipoxygenase- and cyclo-oxygenase-mediated metabolism of arachidonic acid. Biochem. Pharmacol.36, 3463–3470 (1987).

    Article  PubMed  Google Scholar 

  12. C. A. Winter, E. A. Risley and G. W. Nuss,Carrageenin-induced oedema in the hind paw of the rat as an assay for anti-inflammatory drugs. Proc. Soc. Exp. Biol. Med.111, 544–547 (1962).

    Google Scholar 

  13. I. G. Otterness and D. J. Gans,Nonsteroidal anti-inflammatory drugs: an analysis of the relationship between laboratory animal and clinical doses, including species scaling. J. Pharm. Sci.77, 790–795 (1988).

    PubMed  Google Scholar 

  14. L. A. Griffiths,Mammalian metabolism of flavonoids. InThe flavonoids: advances in research. (Eds. J. B. Harbone and T. J. Mabry) pp. 681–718, Chapman & Hall, London 1982.

    Google Scholar 

  15. A. M. Hackett,The metabolism of flavonoid compounds in mammals. Prog. Clin. Biol. Res.213, 177–194 (1986).

    PubMed  Google Scholar 

  16. F. A. Kuehl Jr. and R. W. Egan,Prostaglandins, arachidonic acid and inflammation. Science210, 978–984 (1980).

    PubMed  Google Scholar 

  17. J. R. Vane,Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature231, 232–235 (1971).

    PubMed  Google Scholar 

  18. T. N. Lo, W. F. Saul and S. S. Lau,Carrageenan-stimulated release of arachidonic acid and of lactate dehydrogenase from rat pleural cells. Biochem. Pharmacol.36, 2405–2413 (1987).

    Article  PubMed  Google Scholar 

  19. G. A. Higgs, K. E. Eakins, K. G. Mugridge, S. Moncada and J. R. Vane,The effects of non-steroid anti-inflammatory drugs on leukocyte migration in carrageenin-induced inflammation. Eur. J. Pharmacol.66, 81–86 (1980).

    Article  PubMed  Google Scholar 

  20. G. A. Higgs,The effects of lipoxygenase inhibitors in anaphylactic and inflammatory responses in vivo. Prostagl. Leukotr. Med.13, 89–92 (1984).

    Article  Google Scholar 

  21. G. A. Higgs, R. L. Follenfant and L. G. Garland,Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids: effects on acute inflammatory responses. Br. J. Pharmacol.94, 547–551 (1988).

    PubMed  Google Scholar 

  22. R. A. Kreisle, C. W. Parker, G. L. Griffin, R. M. Senior and M. W. Stenson,Studies of leukotriene B 4-specific binding and function in rat polymorphonuclear leukocytes: absence of a chemotactic response. J. Immunol.134, 3356–3363 (1985).

    PubMed  Google Scholar 

  23. S. J. Foster, M. E. McCormick, A. Howarth and D. Aked,Leukocyte recruitment in the subcutaneous sponge implant model of acute inflammation in the rat is not mediated by leukotriene B 4. Biochem. Pharmacol.35, 1709–1717 (1986).

    Article  PubMed  Google Scholar 

  24. M. Di Rosa, J. M. Papadimitriou and D. A. Willoughby,A histopathological and pharmacological analysis of the mode of action of non-steroidal anti-inflammatory drugs. J. Pathol.105, 239–256 (1971).

    Article  PubMed  Google Scholar 

  25. M. J. Alcaraz and A. Villar,Anti-inflammatory activity of natural phenolic compounds. InHandbook of free radicals and antioxidants in biomedicine, vol. 2. (Eds. J. Miquel, H. Weber and A. T. Quintanilha) pp. 77–85, CRC Press, Boca Raton 1989.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferrándiz, M.L., Alcaraz, M.J. Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents and Actions 32, 283–288 (1991). https://doi.org/10.1007/BF01980887

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01980887

Keywords

Navigation