Monoamine Oxidase Inhibitory Components from the Roots of Sophora flavescens

  • Hwang Ji-Sang (College of Pharmacy, Chungbuk National University) ;
  • Lee Seon A (College of Pharmacy, Chungbuk National University) ;
  • Hong Seong Su (College of Pharmacy, Chungbuk National University) ;
  • Lee Kyong Soon (College of Pharmacy, Chungbuk National University) ;
  • Lee Myung Koo (College of Pharmacy, Chungbuk National University, Research Center for Bioresource and Health, Chungbuk National University) ;
  • Hwang Bang Yeon (College of Pharmacy, Chungbuk National University) ;
  • Ro Jai Seup (College of Pharmacy, Chungbuk National University)
  • Published : 2005.02.01

Abstract

In our search for monoamine oxidase (MAO) inhibitors from natural resources, we found that the methanol extract of the roots of Sophora flavescens showed an inhibitory effect on mouse brain monoamine oxidase (MAO). Bioactivity-guided isolation of the extract yielded two known flavonoids, formononetin (1) and kushenol F (2), as active compounds along with three inactive compounds, oxymatrine (3), trifolirhizin (4), and ${\beta}$-sitosterol (5). Formononetin (1) and kushenol F (2) showed significant inhibitory effects on MAO in a dose-dependent manner with $IC_{50}$ values of 13.2 and $69.9\;{\mu}M$, respectively. Formononetin (1) showed a slightly more potent inhibitory effect against MAO-B ($IC_{50}:\;11.0\;{\mu}M$) than MAO-A ($IC_{50}:\;21.2\;{\mu}M$). Kushenol F (2) also preferentially inhibited the MAO-B activity than MAO-A activity with the $IC_{50}$ values of 63.1 and $103.7\;{\mu}M$, respectively.

Keywords

References

  1. Abell, C. W. and Kwan, S. W., Molecular characterization of monoamine oxidase A and B. Prog. Nucl. Acids Res. Mol. Biol., 65, 129-156 (2001) https://doi.org/10.1016/S0079-6603(00)65004-3
  2. Bach, A. W., Lan, N. C., Johnson, D. L., Abell, C. W., Bembenek, M. E., Kwan, S. W., Seeburg, P. H., and Shih, J. C., cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc. Natl. Acad. Sci. U.S.A., 85, 4934-4938 (1988) https://doi.org/10.1073/pnas.85.13.4934
  3. Benedetti, M. S. and Dostert, P., Monoamine oxidase: from physiology and pathophysiology to the design and clinical application of reversible inhibitors. In Testa, B. (Eds.) Advances in Drug Research, vol. 23. Academic Press, New York, pp.65-125 (1992)
  4. Jo, Y. S., Huong, D. T., Bae, K., Lee, M. K., and Kim, Y. H., Monoamine oxidase inhibitory coumarin from Zanthoxylum schinifolium. Planta Med., 68, 84-85 (2002) https://doi.org/10.1055/s-2002-20056
  5. Jung, B. S. and Shin, M. K., Encyclopedia of illustrated Korean natural drugs. Young Lim Sa, Seoul, pp707-708 (1989)
  6. Kalgutkar, A. S., Castagnoli, N. J., and Testa, B., Selective inhibitors of monoamine oxidase as probes of its catalytic site and mechanism. Med. Res. Rev., 4, 325-388 (1995) https://doi.org/10.1002/med.2610150406
  7. Kraml, M., A rapid microfluorimetric determination of monoamine oxidase. Biochem. Pharmacol., 14, 1684-1686 (1965) https://doi.org/10.1016/0006-2952(65)90025-0
  8. Lee, M. K., Hwang, B. Y., Lee, S. A., Oh, G. J., Choi, W. H., Hong, S. S., Lee, K. S., and Ro, J. S., 1-Methyl-2-undecyl- 4(1H)-quinolone as an irreversible and selective inhibitor of type B monoamine oxidase. Chem. Pharm. Bull., 51, 409-411 (2003) https://doi.org/10.1248/cpb.51.409
  9. Lee, S., Kim, K. S, Shim, S. H., Park, Y. M., and Kim, B. K. Constituents from the non-polar fraction of Artemisia apiacea. Arch. Pharm. Res., 26, 902-905 (2003) https://doi.org/10.1007/BF02980197
  10. Naoi, M. and Nagatsu, T., Quinoline and quininaldines as naturally occurring inhibitors specific for type A monoamine oxidase. Life Sci., 40, 1075-1082 (1987) https://doi.org/10.1016/0024-3205(87)90570-4
  11. Park, J. A., Kim, H. J., Jin, C., Lee, K. T., and Lee, Y. S., A new pterocarpan, (-)-maackiain sulfate, from the roots of Sophora subprostrata. Arch. Pharm. Res., 26, 1009-1013 (2003) https://doi.org/10.1007/BF02994750
  12. Ro, J. S., Lee, S. S., Lee, K. S., and Lee, M. K., Inhibition of type A monoamine oxidase by coptisine in mouse brain. Life Sci., 70, 639-645 (2001) https://doi.org/10.1016/S0024-3205(01)01437-0
  13. Ryu, S. Y., Lee, H. S., Kim, Y. K., and Kim, S. H., Determination of Isoprenyl and lavandulyl positions of flavonoids from Sophora flavescens by NMR experiment. Arch. Pharm. Res., 20, 491-495 (1997) https://doi.org/10.1007/BF02973946
  14. Sekine, T., Saito, K., Minami, R., Arai, N., Suzuki, H., Koike, Y., and Murakoshi, I., A new lupin alkaloid, (-)-leontalbinine Noxide, in Sophora flavescens var. angustifolia seeds and its synthesis by biomimetic transformation from (+)-matrine Noxide. Yakugaku Zasshi, 113, 53-62 (1993) https://doi.org/10.1248/yakushi1947.113.1_53
  15. Shih, J. C., Chen, K., and Ridd, M. J., Monoamine oxidase: from genes to behavior. Annu. Rev. Neurosci., 22, 197-217 (1999) https://doi.org/10.1146/annurev.neuro.22.1.197
  16. Suzuki, O., Katsumata, Y., Oya, M., Chari, V. M., Vermes, B., Wagner, H., and Hostettmann, K., Inhibition of type A and type B monoamine oxidases by naturally occurring xanthones. Planta Med., 42, 17-21 (1981) https://doi.org/10.1055/s-2007-971540
  17. Tang, W. and Eisenbrand, G., Chinese drugs of plant origin. Springer-Verlag, New York, pp. 931-943 (1992)
  18. Thomas, T., Monoamine oxidase-B inhibitors in the treatment of Alzheimer's disease. Neurobiol. Aging, 21, 343-348 (2000) https://doi.org/10.1016/S0197-4580(00)00100-7
  19. Thull, U., Kneubuhler, S., Testa, B., Borges, M. F. M., and Pinto, M. M. M., Substituted xanthones as selective and reversible monoamine oxidase A inhibitors. Pharm. Res., 10, 1187-1190 (1993) https://doi.org/10.1023/A:1018924503552
  20. Wu, L, J., Miyase, T., Ueno, A., Kuroyamagi, M., Noro, T., and Fukushima, S., Studies on the constituents of Sophora flavescens III. Yakugaku Zasshi, 105, 736-741 (1985) https://doi.org/10.1248/yakushi1947.105.8_736
  21. Yamada, M. and Yasuhara, H., Clinical pharmacology of MAO inhibitors: Safety and future. Nerurotoxicology, 25, 215-221 (2004) https://doi.org/10.1016/S0161-813X(03)00097-4