Skip to main content
SpringerLink
Log in

Pharmacological activities of flavonoids (III) structure-activity relationships of flavonoids in immunosuppression

  • Original Articles
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Effects of twenty-one different flavonoids and their related compounds on the phagocytosis of colloidal carbon by macrophages in liver and spleen, humoral immune responses against bacterial α-amylase and cellular immune responses against oxazolone and dinitrofluorobenzene were studiedin vivo andin vitro. It was shown that most of the flavonoids accelerated significantly the phagocytosis, and they suppressed significantly not only humoral and cellular immune responses but also the development of immunological memory after the antigenic stimulation. Especially, malvin was the most active in phagocysis, and disodium cromoglycate and morin were the most active in humoral and cellular immunosuppression, respectively. Daidzein had the most potent inhibitory activity in the development of memory cells. The structure-activity relationships of the flavonoids in immunosuppression became apparant from these results: 1. The presence of C2–3 double bond and C4 ketone group in C-ring was important for their immunosuppressive activity. 2. Flavonoids with benzene ring at 2 or 3 position in C-ring showed the almost same activities. 3. The opening of C-ring did not affect their immunosuppressive activity. 4. The glycosylated flavonoids at 3 position in C-ring were less potent than their aglycones. 5. Di- or tri-hydroxylated flavonoids in B-ring were more potent than mono-hydroxylated. 6. Chromanochromanone also had the immunosuppressive activity.

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

Access this article

Log in via an institution

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

Literature cited

  1. Middleton, E. Jr.: The flavonoids.Trends in Pharmacol. Sci. 5, 335. (1984).

    CAS  Google Scholar 

  2. Gupta, M. B., Bhalla, T. N., Gupta, G.P., Mitra, C. R. and Bhargava, K. P.: Anti-inflammatory activity of taxifolin.Japan. J. Pharmacol. 21, 377 (1971).

    Article  CAS  Google Scholar 

  3. Hikino, H., Taguchi, T., Fujimura, H. and Hiramatsu, Y.: anti-inflammatory principles ofCaesalpinia sappan wood and ofHaematoxylon compechianum wood.Planta Med. 31, 216 (1977).

    Google Scholar 

  4. Parmar, N. S. and Ghosh, M. N.: Anti-inflammatory activity of gossypin, a bioflavonoid isolated fromHibiscus vitifolius L.Ind. J. Pharmac. 10, 277 (1978).

    CAS  Google Scholar 

  5. Fourie, T. G. and Snyckers, F. O.: A flavone with anti-inflammatory activity from the roots ofRhus undulata.J. Nat. Prod. 47, 1057 (1984).

    Article  PubMed  CAS  Google Scholar 

  6. Villar, A., Gasco, M. A. and Alcaraz, M. J.: Anti-inflammatory and antiulcer properties of hypolaetin-8-glycoside, a novel plant flavonoid.J. Pharm. Pharmacol. 36, 820 (1984).

    PubMed  CAS  Google Scholar 

  7. Al-Meshal, I. A., Tarig, M., Parmar, N. S. and Ageel, A. M.: Anti-inflammatory activity of the flavonoid fraction of hat.Agents and Actions 17, 379 (1985).

    Article  CAS  Google Scholar 

  8. Suganda, A. G., Amoros, M., Fauconnier, B. and Girre, L.: Antiherpetic and antipoliomyeletic effects ofMatricaria inodora L.Planta. Med. Phytother. 18, 215 (1984).

    CAS  Google Scholar 

  9. Cazzulani, P., Panzarasa, R., De Stefani, C. and Graziani, G.: Mechanism of flavoxate antispasmodic activity comparativein vitro studies.Arch. Int. Pharmacodyn. 274, 189 (1985).

    PubMed  CAS  Google Scholar 

  10. Horinchi, T., Fujuki, H., Hakii, H., Suganuma, M., Yamashita, K. and Sugimura, T.: Modulation of phorbol ester receptors in mouse skin by application of quercetin.Jpn. J. Can. Res. 77, 526 (1986).

    Google Scholar 

  11. Suzuki, K. and Hosokawa, T.: Immunosuppressants containing flavonoids.Jpn. Kokai Tokyo Koho. Pat. No. 88233917 (1988).

  12. Berg, A. U. J., Baron, D. P. and Berg, P. A.: Immunomodulating properties of cianidanol on responsiveness and function of human peripheral blood T-cells, and K-cells.Int. J. Immunopharmacol. 10, 387 (1988).

    Article  PubMed  CAS  Google Scholar 

  13. Ito, N., Ogawara, H. and Watanabe, S.: Preparation of isoflavone derivatives and salts thereof as oncostic and immunosuppressive agents and pharmaceutical composition containing them.PCT. Int. Appl. Pat. No. 8702982 (1987).

  14. Schwartz, A., Sandra, L. S. and Middleton, E. Jr.: Quercetin inhibition of the induction and function of cytotoxic T lymphocyte.Immunopharmacol. 4, 125 (1982).

    Article  CAS  Google Scholar 

  15. Zhong, F., Jiang, Y., Wu, F., Shu, R., Cai, X. and Tan, J.: Effect of the total flavone ofHippophae rhamnoides fruits on mouse cell immune function.Zhongcaoyao 20, 331 (1989).

    CAS  Google Scholar 

  16. Yasukawa, K., Takido, M., Takeuchi, M. and Nitta, K.: Effect of flavonoids on tumor promotor’s activity.Prog. Clin. Biol. Med. 280, 247 (1988).

    CAS  Google Scholar 

  17. Nagai, H., Osuga, K. and Koda, A.: Inhibition of hypersensitivity reactions by soluble derivatives of baicalein.Japan. J. Pharmacol. 25, 763 (1975).

    Article  CAS  Google Scholar 

  18. Sankawa, U. and Chun, Y. T.: Anti-allergic substances from Chinese medicinal plant. Advances in Chinese medicinal material research. World Scientific Publ. Co., Singapore, p. 171 (1985).

    Google Scholar 

  19. Kinoshita, G., Nakamura, F. and Maruyama, T.: Immunological studies on polysaccharide fraction from crude drugs.Shoyakugaku Zasshi 40, 325 (1986).

    Google Scholar 

  20. Kim, C. J., Choi, C. S. and Cho, S. K.: The effects of Cantharis polysaccharide fraction on the inflammation and immune reaction. in press (1991).

  21. Siena, S., Bregni, M., Formosa, A., Brando, B., Marenco, P., Lappi, D. A., Bonadonna, G. and Gianni, A. M.: Immunotoxin-mediated inhibition of chronic lymphocytic leukemia cell proliferation in human.Cancer Res. 49, 3328 (1989).

    PubMed  CAS  Google Scholar 

  22. Xue, W. L. and Matthew, R. W.: RadixTripterygium wilfordii-a Chinese herbal medicine with potent immunosuppressive properties.Transplantation 50, 82 (1990).

    Article  Google Scholar 

  23. Hemi, H., Kitame, F., Ishida, N., Kusano, G. and Kondo, Y.: Inhibitory effects on lymphocyte proliferation of some naturally occurring compounds obtained from medicinal plant.Proc. Symp. Wakan-Yaku 11, 61 (1978).

    Google Scholar 

  24. Altmann, W. A., Elson, C. E. and Cook, M. E.: The immunosuppressive activity of the plant metabolite geraniol in chicks.Fed. Am. Soc. Expt. Biol. 4, A935 (1990).

    Google Scholar 

  25. Ammellal M., Bronner, C., Briancon, F., Haag, M., Anton, R. and Landry, Y.: Inhibition of mast cell histamine release by flavonoids and biflavonoids.Planta Med. 51, 16 (1985).

    Article  Google Scholar 

  26. Middleton, E. Jr. and Drzewiecki, G.: Effects of flavonoids and transient metal cations on antigen-induced histamine release from human basophils.Biochem. Pharmacol. 31, 1449 (1982).

    Article  PubMed  CAS  Google Scholar 

  27. Bennett, J. P., Gompert, B. D. and Wollenweber, E.: Inhibitory effects of natural flavonoids on secretion from mast cells and neutrophils.Arzneim-Forsch. 31, 433 (1981).

    CAS  Google Scholar 

  28. Kim, C. J. and Chung, J. M.: Pharmacological activities of flavonoids (I). Relationships of chemical structure of flavonoids and their inhibitory activity of hypersensitivities.Yakhak Hoeji 34, 348 (1990).

    CAS  Google Scholar 

  29. Kim, C. J., Su, S. K., Joo, J. H. and Cho, S. K.: Pharmacological activities of flavonoids (II). Relationships of anti-inflammatory and actigranulomatous actions.Yakhak Hoeji 34, 407 (1990).

    CAS  Google Scholar 

  30. Kubo, M., Nagao, T., Matsuda, H., Tani, T., Arichi, S. and Kitagawa, I.: Studies on moutan cortex IX. On the phagocytosis of the mouse reticuloendothelial system (1).Yakugaku Zasshi 105, 26 (1985).

    PubMed  CAS  Google Scholar 

  31. Harris, H. F.: On the rapid conversion of haematoxylin into haematein in staining reactions.J. Appl. Microsc. Lab. Meth. 3, 778 (1900).

    Google Scholar 

  32. Takata, M., Kumagai, A. and Kitagawa, M.: Mechanism of immunosuppression induced by Licorice root extract (LX).Proc. Symp. Wakan-Yaku 6, 19 (1972).

    Google Scholar 

  33. Hamaoka, T., Kitagawa, M., Matsuoka, Y. and Yamamura, Y.: Antibody production in mice. I. The analysis of immunological memory.Immunol. 17, 55 (1969).

    CAS  Google Scholar 

  34. Ramellini, G. and Meldolesi, J.: Liver protection by silymarin:In vitro effect of dissociated rat hepatocyte.Arzneim-Forsch. 26, 69 (1976).

    CAS  Google Scholar 

  35. Somogyi, M.: Notes on sugar determination.J. Biol. Chem. 195, 19 (1952).

    CAS  Google Scholar 

  36. Kishore, V. and Latman, N.: Effect of nutritional copper deficiency on adjuvant arthritis and immuno-competence in the rats.Agents and Actions 140, 274 (1984).

    Article  Google Scholar 

  37. Moorhead, J. W.: Soluble factors in tolerance and contact sensitivity to 2,4-dinitrofluorobenzene in mice.J. Exp. Med. 150, 1432 (1979).

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  39. Varma, S. D.: Inhibition of aldose reductase by flavonoids.Proc. Clin. Biol. Res. 213, 343 (1986).

    CAS  Google Scholar 

  40. Middleton, E. Jr. and Drzewiecki, G.: Flavonoid inhibition of human basophil histamine release stimulated by various agents.Biochem. Pharmacol. 33, 3333 (1984).

    Article  PubMed  CAS  Google Scholar 

  41. Landolfi, R., Mower, R. L. and Steiner, M.: Modification of platelet function and arachidonic acid metabolism by bioflavonoids.ibid. 33, 1525 (1984).

    Article  PubMed  CAS  Google Scholar 

  42. Hus, K. K. and Chen, F. C.: Structure-activity relationship of substitued flavonoids.Tai-Wan Ko Hsueh 27, 23 (1973).

    Google Scholar 

  43. Mora, A., Paya, M., Rios, L. and Alcaraz, M. J.: Structure-activity relationships of polymeth-oxyflavones and other flavonoids as inhibitors of non-enzymatic lipid peroxidation.Biochem. Pharmacol. 40, 793 (1990).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathophysiology, College of Pharmacy, Chung-Ang University, 156-756, Seoul, Korea

    Chang-Johng Kim & Seung Kil Cho

Authors
  1. Chang-Johng Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seung Kil Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, CJ., Cho, S.K. Pharmacological activities of flavonoids (III) structure-activity relationships of flavonoids in immunosuppression. Arch. Pharm. Res. 14, 147–159 (1991). https://doi.org/10.1007/BF02892020

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02892020

Keywords

Search

Navigation