Effect of Plant Flavonoids on Immune and Inflammatory Cell Function

  • Elliott MiddletonJr.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 439)


The flavonoids are a large group of naturally occurring phenylchromones found in fruits, vegetables, grains, bark, roots, stems, flowers, tea, and wine. Up to several hundred milligrams are consumed daily in the average Western diet. Only limited information is available on the absorption, distribution, metabolism, and excretion of these compounds in man. Some compounds are absorbed, however, and measurable plasma concentrations are achieved which could have pharmacological relevance.

A variety of in vitro and in vivo experiments have shown that selected flavonoids possess antiallergic, antiinflammatory, antiviral and antioxidant activities. Moreover, acting by several different mechanisms, particular flavonoids can exert significant anticancer activity including anticarcinogenic properties and even a prodifferentiative activity, amongst other modes of action. Certain flavonoids possess potent inhibitory activity against a wide array of enzymes, but of particular note is their inhibitory effects on several enzyme systems intimately connected to cell activation processes such as protein kinase C, protein tyrosine kinases, phospholipase A2, and others. Evidence suggests that only activated cells are susceptible to the modulating effects of flavonoids, i.e. cells which are responding to a stimulus. The stimulated activities of numerous cell types, including mast cells, basophils, neutrophils, eosinophils, T & B lymphocytes, macrophages, platelets, smooth muscle, hepatocytes, and others, can be influenced by particular flavonoids. On balance, a considerable body of evidence suggests that plant flavonoids may be healthpromoting, disease-preventing dietary compounds.


Histamine Release Eosinophil Cationic Protein Allergic Rhinoconjunctivitis Plant Flavonoid Include Mast Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anné, S.; Agarwal, R.; Nair, M. P.; Schwartz, A.; Middleton, E. Inhibition of endotoxin-induced expression of intercellular adhesion molecule-1 and of leukocyte adhesion to endothelial cells by the plant flavonol quercetin. J. Allergy and Clin. Immunol., 1994, 93, 276 (abstract).Google Scholar
  2. Bochner, B. Cellular Adhesion in Inflammation. In Allergy: Principles and Practice; E. Middleton; C. E. Reed; E. F. Ellis; N. F. Adkinson; J. W. Yunginger; W. W. Busse, Eds., Mosby Yearbook: St. Louis, MO. 1998.Google Scholar
  3. Brinkworth, R.; Stoermer, M. J.; Fairlie, D. P. Flavones are inhibitors of HIV-1 proteinase. Biochem. Biophys. Res. Comm., 1992, 188, 631.PubMedCrossRefGoogle Scholar
  4. Ferriola, P. C.; Cody, V.; Middleton, E. Protein kinase C inhibition by plant flavonoids, kinetic mechanisms and structure-activity relationships. Biochem. Pharmacol., 1989, 38, 1617.PubMedCrossRefGoogle Scholar
  5. Fesen, M. R.; Kohn, K. W.; Leteurtre, F.; Pommier, Y. Inhibitors of human immunodeficiency virus integrase. Proc. Nat. Acad. Sci. U.S.A., 1993, 90, 2399.CrossRefGoogle Scholar
  6. Gerritsen, M.E.; Carley, W. H.; Ranger, G. E. Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression. Am. J. Pathol., 1995, 147, 278–292.PubMedGoogle Scholar
  7. Gryglewski, R. J.; Korbut, R.; Robak, J.; Swies, J. On the mechanism of antithrombotic action of flavonoids. Biochem. Pharmacol., 1987, 36, 317–322.PubMedCrossRefGoogle Scholar
  8. Imoto, M.; Yamashita, Y.; Sawa, T.; Kurasawa, S.; Naganawa, H.; Takeuchi, T.; Bao-quan, Z.; Umezawa, K. Inhibition of cellular phosphatidylinositol turnover by psi-tectorigenin. FEBS Letters 1988, 230, 43–46.PubMedCrossRefGoogle Scholar
  9. Kaul, T. N.; Middleton, E.; Ogra, P. L. Antiviral effect of flavonoids on human viruses. J. Med. Virol, 1985, 15, 71.PubMedCrossRefGoogle Scholar
  10. Kuhnau, J. The flavonoids: a class of semi essential food components: their role in human nutrition. World Rev. Nutr. Diet., 1976, 24, 117–191.PubMedGoogle Scholar
  11. Lane, P. J. L.; Ledbetter, J. A.; McConnell, F. N.; Draves, K.; Deans, J.; Schieven, G. L.; Clark, E. A. The role of tyrosine phosphorylation in signal transduction through surface Ig in human B cells: inhibition of tyrosine phosphorylation prevents intracellular calcium release. J. Immunol., 1991, 146, 715–722.PubMedGoogle Scholar
  12. Lee, T.-P.; Matteliano, M. L.; Middleton, E. Effect of quercetin on human polymorphonuclear leukocyte lysosomal enzyme release and phospholipid metabolism. Life Sci., 1982, 31, 2765.PubMedCrossRefGoogle Scholar
  13. Maalej, N.; Demrow, H. S.; Slane, P. R.; Folts, J. D. Antithrombotic effects of flavonoids in red wine. In Wine: Nutritional and Therapeutic Benefits; T. R. Watkins, ed.; American Chemical Society, Symposium Series; Washington, 1997; pp. 247–260.Google Scholar
  14. Maxwell, S. R. J. Wine Antioxidants and their Impact on Antioxidant Activity in vivo. In Wine: Nutritional and Therapeutic Benefits; T. R. Watkins, ed.; American Chemical Society, Symposium Series; Washington, 1997; pp. 150–165.Google Scholar
  15. Middleton, E. The Flavonoids as Potential Therapeutic Agents. In ImmunoPharmaceuticals; E. S. Kimball, Ed. CRC Press, Boca Raton, FL. 1996, pp.227–257.Google Scholar
  16. Middleton, E.; Drzewiecki, G. Flavonoid inhibition of human basophil histamine release stimulated by various agents. Biochem. Pharmacol, 1982, 31, 1449.PubMedCrossRefGoogle Scholar
  17. Middleton, E.; Drzewiecki, G.; Krishnarao, D. P. Quercetin: an inhibitor of antigen-induced human basophil histamine release. J. Immunol., 1981, 127, 546.PubMedGoogle Scholar
  18. Middleton, E.,Jr.; Kandaswami, C. The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation, and cancer. In Advances in Flavonoid Research; J. B. Harborne, ed.; Chapman and Hall, London, 1993; pp. 619–652.Google Scholar
  19. Middleton, E.,Jr.; Kandaswami, C. Free radical scavenging and antioxidant activity of plant flavonoids. Adv. Exp. Med. Biol., 1994, 366, 251–366.Google Scholar
  20. Mookerjee, B. K.; Lee, T.-P.; Lippes, H. A.; Middleton, E. Some effects of flavonoids on lymphocyte proliferative processes. J. Immunopharmacol., 1986, 8, 371.PubMedCrossRefGoogle Scholar
  21. Nishioka, H.; Imoto, M.; Sawa, T.; Hamada, M.; Naganawa, H.; Takeuchi, T.; Umezawa, K. Screening of phosphatidylinositol kinase inhibitors from streptomyces. Antibiot., 1989, 42, 823–825.CrossRefGoogle Scholar
  22. Schwartz, A.; Middleton, E. Comparison of the effects of quercetin with those of other flavonoids on the generation and effector function of cytotoxic T lymphocytes. Immunopharmacology 1984, 7, 115.PubMedCrossRefGoogle Scholar
  23. Sloan, R.; Boran-Rogotzky, R.; Ackerman, S. J.; Drzewiecki, G.; Middleton, E. The effect of plant flavanoids on eosinophil degranulation. J. Allergy Clin. Immunol., 1991, 87, 282 (abst.).CrossRefGoogle Scholar
  24. Spedding, G.; Ratty, A.; Middleton, E. Inhibition of reverse transcriptases by flavanoids. Antiviral Res., 1989, 12, 99.PubMedCrossRefGoogle Scholar
  25. Tauber, A. L; Fay, J. R.; Marietta, M. A. Flavonoid inhibition of human neutrophil NADPH-oxidase. Biochem. Pharmacol, 1984, 33, 1367–1369.PubMedCrossRefGoogle Scholar
  26. Verma, A. K.; Johnson, J. A.; Gould, M. N.; Tanner, M. A. Inhibition of 7,12-dimethylbenz[a]anthracene and N-nitroso methylurea-induced rat mammary cancer by dietary flavonol quercetin. Cancer Res., 1988, 48, 5754.PubMedGoogle Scholar
  27. Yamada, H.; Nagai, T.; Takemoto, N.; Endoh, H.; Kiyohara, H.; Kawamura, H.; Otsuka, Y. Plantagoside, a novel alpha-mannosidase inhibitor isolated from the seeds of Plantago asiatica, suppresses immune response. Biochem. Biophys Res. Comm., 1989, 165, 1292.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Elliott MiddletonJr.
    • 1
  1. 1.Chebeague Island Institute of Natural Product ResearchChebeague IslandUSA

Personalised recommendations