Abstract
Various flavonoid derivatives were previously reported to possess the inhibitory activity on cyclooxygenase/lipoxygenase. And these properties of flavonoids might contribute to their antiinflammatory activityin vivo. In this study, several polyhydroxylated/methoxylated flavonoid derivatives such as oroxylin A, wogonin, skullcapflavone II, tectorigenin and iristectorigenin A were isolated from the medicinal plants. These compounds were evaluated for their inhibitory effects on cyclooxygenase/lipoxygenase from the homogenate of human plateletsin vitro. It was found that isoflavones including daidzein and tectorigenin possessed the inhibitory activity on cyclooxygenase, although the potency of inhibition was far less than that of indomethacin. In addition, oroxylin A, baicalein and wogonin inhibited 12-lipoxygenase activity without affecting cyclooxygenase, which suggested that 5,6,7- or 5,7,8-trisubstitutions of A-ring of flavone gave favorable results. The IC50 values of oroxylin A and NDGA aginst 12-lipoxygenase were found to be 100 and 1.5 uM, respectively.
Similar content being viewed by others
References Cited
Baumann, J., Bruchhausen, F. V. and Wurm, G., Flavonoids and related compounds as inhibitors of arachidonic acid peroxidation.Prostaglandins, 20, 627–639 (1980).
Croset, M., Stereospecific inhibition of PGH2-induced platelet aggregation by lipoxygenase products of icosaenoic acids.Biochem. Biophys. Res. Comm., 112, 878–883 (1983).
Ferrandiz, M. L., Ramachandran Nair, A. G. and Alcaraz, M. J., Inhibition of sheep platelet arachidonate metabolism by flavonoids from Spanish and Indian medicinal herbs.Pharmazie, 45, 206–208 (1990).
Gil, B., Sanz, M. J., Terencio, M. C., Ferrandiz, M. L., Bustos, G., Paya, M., Gunasegaran, R. and Alcaraz, M. J., Effects of flavonoids onNaja naja and human recombinant synovial phospholipase A2 and responses in mice.Life Sci., 54, PL333–338 (1994).
Havsteen, B., Flavonoids, a class of natural products of high pharmacological potency.Biochem. Pharmacol., 32, 1141–1148 (1983).
Kim, H. P., Mani, I., Iversen, L. and Ziboh, V. A., Effects of naturally-occurring flavonoids and biflavonoids on epidermal cyclooxygenase and lipoxygenase from guinea-pigs.Prostag. Leukot. Essen. Fatty Acids, 58, 17–24 (1998).
Kim, H. P., Son, K. H., Chang, H. W. and Kang, S. S., Flavonoids: Potential anti-inflammatory agents.Nat. Prod. Sci. (Korea), 2, 1–8 (1996).
Kimura, Y., Okuda, H., Nomura, T., Fukai, T. and Arichi, S., Effects of flavonoids and related compounds from mulberry tree on arachidonate metabolism in rat platelet homogenates.Chem. Pharm. Bull., 34, 1223–1227 (1986).
Kimura, Y., Okuda, H., Taira, Z., Shoji, N., Takemoto, T. and Arichi, S., Studies on Scutellaria radix; IX New component inhibiting lipid peroxydation in rat liver.Planta Med. 51, 290–294 (1984).
Laughton, M. J., Evans, P. J., Moroney, M. A., Hoult, J. R. S. and Halliwell, B., Inhibition of mammalian 5-lipoxygenase and cyclooxygenase by flavonoids and phenolic dietary additives.Biochem. Pharmacol., 42, 1673–1681 (1991).
Lee, S. J., Baek, H. J., Lee, C. H. and Kim, H. P., Antiinflammatory activity from Pueraria radix and biochanin A derivatives.Arch. Pharm. Res., 17, 31–35 (1994).
Lee, S. O., Woo, W. S., Woo, E. H. and Kim, K. S., Isoflavonoids ofBelamcanda chinensis.Kor. J. Pharmacogn., 20, 219–222 (1989).
Middleton, E. and Kandaswami, C., Effects of flavonoids on immune and inflammatory cell functions.Biochem. Pharmacol., 43, 1167–1179 (1992).
Morita, N., Shimokoriyama, M., Shimizu, M. and Arisawa, M., Studies on medicinal resources. XXXII. The components of rhizome ofIris tectorum Maximowicz (Iridaceae).Chem. Pharm. Bull., 20, 730–733 (1972).
Reddy, G. R., Ueda, N., Hada, T., Sackeyfio, A. C., Yamamoto, S., Hano, Y., Aida, M. and Nomura, T., A Prenylflavone, artonin E, as arachidonate 5-lipoxygenase inhibitor.Biochem. Pharmacol., 41, 115–118 (1991).
Sekiya, K. and Okuda, H., Selective inhibition of platelet lipoxygenase by baicalein.Biochem. Biophys. Res. Comm., 105, 1090–1095 (1982).
Siegel, M. I., McConnell, R. T., Abrahams, S. L., Porter, N. A. and Cuatrecasas, P., Regulation of arachidonate metabolism via lipoxygenase and cyclooxygenase by 12-HPETE, the product of human platelet lipoxygenase.Biochem. Biophys. Res. Comm. 89, 1273–1280 (1979).
Shin, K. H., Kang, S. S., Kim, H. J. and Shin, S. W. Isolation of an aldose reductase inhibitor from the fruits ofVitex rotundifolia.Phytomedicine, 1, 145–147 (1994).
Welton, A. F., Hurley, J. and Willi, P., Flavonoids and arachidonic acid metabolism. In Plant flavonoids in biology and medicine. II: Biochemical, cellular, and medicinal properties., Codyet al. (eds.), 1988, Alan R. Liss, New York, pp. 301–312.
Yamaki, M., Kato, T., Kashihara, M. and Takagi, S. Isoflavones ofBelamcanda chinensis.Planta Med., 56, 335 (1990).
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 Scutellaria radix.Kor. J. Pharmacogn., 23, 234–239 (1992).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
You, K.M., Jong, HG. & Kim, H.P. Inhibition of cyclooxygenase/lipoxygenase from human platelets by polyhydroxylated/methoxylated flavonoids isolated from medicinal plants. Arch Pharm Res 22, 18–24 (1999). https://doi.org/10.1007/BF02976430
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02976430