Advertisement

Archives of Pharmacal Research

, Volume 16, Issue 4, pp 283–288 | Cite as

Evaluation of some flavonoids as potential bradykinin antagonists

  • Hye Sook Yun-Choi
  • Sung Hyun Chung
  • Young Joo Kim
Research Article

Abstract

Fourteen flavonoids were evaluated for their effects as potential bradykinin (BK) antagonists. The compounds were evaluated in severalin vitro andin vivo (oral administration) systems; inhibition of BK induced contractions in isolated rat ileum and uterus, antagonistic effects of BK induced plasma extravasation, reduction of acetic acid induced writhing nociception and protection from endotoxic shock. Skullcapflavone II (3), baicalein (5), 5-methoxyflavone (11), 6-methoxyflavone (12) and 2′-methoxyflavone (14) showed effects in all the tests although the order of potency were somewhat varied.

Key words

Potential bradykinin (BK) antagonists Skullcapflavone II Baicalein 5-Methoxyflavone 6-Methoxyflavone 2′-Methoxyflavone 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References Cited

  1. Burch, R. M., Farmer, S. G. and Steranka, L. R., Bradykinin receptor antagonists.Med. Res. Rev., 10, 237–269 (1990).PubMedCrossRefGoogle Scholar
  2. Bathon, J. M. and Proud, D., Bradykinin antagonists.Annu. Rev. Pharmacol. Toxicol., 31, 129–162 (1991).PubMedCrossRefGoogle Scholar
  3. Christian, S. C., Proud, D. and Cochrane, C. G., Detection of tissue kallikrein in the bronchoalveolar lavage fluid of asthmatic subjects.J. Clin. Invest., 79, 188–197 (1987).CrossRefGoogle Scholar
  4. Chung, S. H., Choi, J. J., Yoo, K. S. and Yun-Choi, H. S., Bradykinin antagonistic activities of Scutellariae radix.Kor. J. Pharmacogn., 22, 192–196 (1991).Google Scholar
  5. Clark, W. G., Kinins and the peripheral and central nervous systems, In Erdos, E. G. (ed.),Handbook of Experimental Pharmacology, Vol. 25 (supplement), Springer-Verlag, 1979, pp. 312–356.Google Scholar
  6. Collier, H. O. and Lee, I. R., Nociceptive responses of guinea pigs to intradermal injections of bradykinin and kallidin-10.Brit. J. Pharmacol., 21, 151 (1963).Google Scholar
  7. Griesbacher, T. and Lembeck, F., Effect of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle in the rabbit.Br. J. Pharmac., 92, 333–340 (1987).Google Scholar
  8. Haddy, F. J., Emerson, T. E. Jr., Scott, J. B. and Daugherty, R. M. Jr., The effect of kinins on the cardiovascular system: in Erdos, E. G. (ed.),Handbook of Experimental Pharmacology, Vol. 25, Springer-Verlag, 1970, pp. 362–384.Google Scholar
  9. Hamberg, U., Vahtera, E. and Moilanen, L., Functionally active alpha2-macroglobulin and kinin release in synovial fluids of rheumatoid arthritis.Agents and Actions, 8, 50 (1978).PubMedCrossRefGoogle Scholar
  10. Harborne, J. B., The flavonoids,Advances in research since 1980, Chapman and Hall, London, 1988.Google Scholar
  11. Hirsch, E. F., Nakajima, T., Oshima, G., Erdos, E. G. and Herman, C. M., Kinin system resoonses in sepsis after trauma in man.J. Surg. Res., 17, 147–153 (1974).PubMedCrossRefGoogle Scholar
  12. Hock, F. J., Wirth, K., Albus, U., Linz, W., Gerhards, H. J., Hoe 140 a new potent and long acting bradykinin-antagonist;in vitro studies.Br. J. Pharmacol., 102, 769–773 (1991).PubMedGoogle Scholar
  13. Holdstock, D. J., Mathias, A. P. and Schachter, M., A comparative study of kinin, kallidin, and bradykinin.Brit. J. Pharmacol., 12, 149–158 (1957).PubMedGoogle Scholar
  14. Kubo, M., Matsuda, H., Kimura, Y., Okuda, H. and Arichi, S., Scutellariae radix. X. Inhibitory effects of various flavonoids on histamine release from rat peritoneal mast cellsin vitro.Chem. Pharm. Bull., 32, 5051–5054 (1984).Google Scholar
  15. Kubo, M., Matsuda, H., Tani, T., Arichi, S., Kimura, Y. and Okuda, H., Studies on Scutellariae radix. XII. Anti-thrombic actions of various flavonoids from Scutellariae radix.Chem. Pharm. Bull., 33, 2411–2415 (1985).PubMedGoogle Scholar
  16. Kyle, D. J., Martin, J. A., Farmer, S. G., Burch, R. M., Design and conformational analysis of several highly potent bradykinin receptor antagonists.J. Med. Chem., 34, 1230–1233 (1991).PubMedCrossRefGoogle Scholar
  17. Mason, D. T. and Melmon, K. L., Effects of bradykinin on forearm venous tone and vascular resistance in man.Circulat. Res. 17, 106–113 (1965).PubMedGoogle Scholar
  18. Proud, D., Kinin formation: Mechanisms and role in inflammatory disorders.Ann. Rev. Immunol., 6, 49–83 (1988).CrossRefGoogle Scholar
  19. Proud, D., Togias, A., Nacleria, R. M., Crush, S. A., Norman, P. S. and Lichtenstein, L. M., Kinins are generatedin vivo following nasal airway chalenge of allergic individuals with allergen.J. Clin. Invest., 72, 1678–1685 (1983).PubMedCrossRefGoogle Scholar
  20. Regoli, D. and Barabe, J., Pharmacology of bradykinin and related kinins.Pharmacol. Rev., 32, 1–46 (1980).PubMedGoogle Scholar
  21. Robinson, J. A., Klodnycky, Loeb, H. S., Racic, M. R. and Gunnar, R. M., Endotoxin, prekallikrein, complement and systemic vascular resistance.Am. J. Med., 59, 61–67 (1975).PubMedCrossRefGoogle Scholar
  22. Schachter, M., Uchida, Y., Longridge, D. J., Labedz, T., Whalley, E. T., Vavrek, R. J. and Stewart, J. M., New synthetic antagonists of bradykinin.Br. J. Pharmacol., 92, 851–855 (1987).PubMedGoogle Scholar
  23. Sharma, J. N., Zeithlin, I. J., Deodhar, S. D. and Buchanan, W. W., Detection of kallikrein-like activity in inflamed synovial tissue.Arch. Int. Pharmacodyn., 262, 279–286 (1983).PubMedGoogle Scholar
  24. Steranka, L. R., Farmer, S. G. and Burch, R. M., Antagonists of bradykinin receptors.FASEB J., 3, 2019–2025 (1989).PubMedGoogle Scholar
  25. Vavrek, R. J. and Stewart, J. M., Competitive antagonists of bradykinin,Peptides, 6, 161–164 (1985).PubMedCrossRefGoogle Scholar
  26. Weipert, J., Hoffmann, H., Siebeck, M. and Whalley, E. T., Attenuation of arterial blood pressure fall in endotoxin shock in the rat using the competitive bradykinin antagonist Lys-Lys-(Hyp2, Thi5,8, DPhe7)-BK (B4148).Br. J. Pharmacol. 94, 282–284 (1988).PubMedGoogle Scholar
  27. Wilson, D. D., de Garavilla, L., Kuhn, W., Togo, J., Burch, R. M. and Steranka, L. R., D-Arg-(Hyp3-D-Phe7)-bradykinin, a bradykinin antagonist, reduces mortality in a rat model of endotoxic shock.Circ. Shock, 27, 93–101 (1989).PubMedGoogle Scholar
  28. Yun-Choi, H. S., Flavonoid components in plants of the Genus Scutellaria,Kor. J. Pharmacogn., 23, 201–210 (1992).Google Scholar
  29. Yun-Choi, H. S., Yoo, K. S., Chung, S. H., Yang, H. S., Choi, J. J. and Kim, Y. J., Flavonoids with bradykinin antagonistic effects from Scutellariae radix.Kor. J. Pharmacogn., 23, 234–239 (1992).Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 1993

Authors and Affiliations

  • Hye Sook Yun-Choi
    • 1
  • Sung Hyun Chung
    • 2
  • Young Joo Kim
    • 1
  1. 1.Natural Products Research InstituteSeoul National UniversitySeoulKorea
  2. 2.College of PharmacyKyung Hee UniversitySeoulKorea

Personalised recommendations