생약추출물의 Cytochrome P450 약물대사 효소계 저해활성

Inhibitory Effects of Medicinal Herbs on Cytochrome P450 Drug Metabolizing Enzymes

  • 발행 : 2002.03.30

초록

The MeOH ext., $CH_2Cl_2$ Frac., EtOAc Frac., n-BuOH Frac., and $H_2O$ Frac. of 23 Korean medicinal herbs were prepared and were tested the inhibitory effects on Cytochrome P450 (Cyp) 1A1/2, 2B1/2, 2E1. Among the tested samples, the extracts of Selaginella tamariscina, Euonymus alatus, Salvia miltiorhiza, Angelica acutiloba, Rheum palmatum, Paeonia moutan, Scutellaria barbata, Tribulus terrestris, Hedyotis diffusa, Curcuma zedoaria, Rehmania glutinosa, Trogopterus xanthipes, Melandryum firmum, Achyranthes bidentata, Leonurus sibricus, Panax ginseng, Paeonia lactiflora, Poncirus trifoliata, Cnidium officinale, Cyperus rotundus, Corydalis ternata showed significant inhibitory effects on Cyp 1A1/2, 2B1/2, 2E1. The $IC_{50}$ values of those extracts were found to be below $50\;{\mu}g/ml$.

키워드

참고문헌

  1. Guengerich, F.P. (1987) Chapterl. Enzymology of rat livercytochrome P-450. In 'Mammalian Cytochrome P-450' Vol.1., by F.P. Guengerich, CRC Press, Florida, pp 1-54
  2. Guengerich, F.P. (1988) Role of cytochrome P-450 enzymesin chemical carcinogenesis and cancer chemotheraphy.Cancer Res. 48: 2946-2954
  3. Guengerich, F.P. (1989) Analysis and characterization ofenzymes. In 'Principles and Methods of Toxicology' Hayes,A.W. ed. Raven Press, NewYork, pp 779-813
  4. Ioannides, C., Lum, P.Y., and Parke, D.V. (1984) CytochromeP448 and the activation of toxic chemicals and carcinogens.Xenobiotica 14: 119-137 https://doi.org/10.3109/00498258409151402
  5. Denison, M.S., Vella, L.M., and Okey, A.B. (1986) Structureand function of the Ah receptor for 2,3,7,8-tetrachloro-dibenzo-p-dioxin. J. Biol. Chem. 261: 3987-3996
  6. Nelson, S.D., Mitchell, J.R., Timbrell, J.A., Snodgrass, W.R.,and Corcoran, G.B. (1976) Isoniazid and iproniazid activa-tion of metabolites to toxic intermediates in man and rat.Science 193: 901-903 https://doi.org/10.1126/science.7838
  7. Lewis, J.G., Stewart, W., and Adams, D.O. (1988) Role ofoxygen radicals in induction of DNA damage by metabolites of benzen. Cancer Res. 48: 4762-4765
  8. Seeff, L.B., Cuccherini, B.A., Zimmerman, H.J., Alder, E.,and Benjamin, S.B. (1986) Acetaminophen hepatotoxicity in alcoholics. Ann. Intl. Med. 104: 399-404 https://doi.org/10.7326/0003-4819-104-3-399
  9. Koop, D.R., Laethem, C.L., and Schnier, G.G. (1989)Identification of ethanol-inducible P450 isozyme 3a (P4502El) as a benzene and phenol hydroxylase. Toxicol. Appl.Pharmacol. 98: 278-288 https://doi.org/10.1016/0041-008X(89)90233-0
  10. English, J.C., and Ander, M.W. (1985) Evidence for themetabolism of N-nitrosodimethylamine and carbon tetra-chloride by a common isozyme of cytochrome P450. DrugMetabol. Dispos. 13: 449-452
  11. Klensler, T.W., Egner, P.A., Dolan, P.M., Groopman, J.D.,and Roebuck, B.D. (1987) Mechanism of protection againstAflatoxin tumorigenicity in rats fed 5-(2-pyraziny1)-4-methyl-1,2-dithio1-3-1hione (oltipraz) and related 1,2-dithio1-3-thiones and 1,2-dithio1 -3-ones. Cancer Res. 47: 4271-4277
  12. Lubet, R.A., Mayer, R.T., Camnon, J.W., Nims, R.W., Burke,M.D., Wolf, T, and Guengerich, F.P. (1985a) Dealkylation ofpentoxyresorufin: A rapid and sensitive assay for measuringinduction of cytochrome P450 by phenobarbital and otherxenobiotics in the rat. Arch. Biochem. Biophys. 238: 43-78 https://doi.org/10.1016/0003-9861(85)90138-9
  13. Lubet, R.A., Nims, R.W., Mayer, T.C., and Schechman, L.M.(1985b) Measurement of cytochrome P450-dependent deal-kylation of alkoxyphenoxazone in hepatic S9s and hepato-cyte homogenates : Eggect of dicumarol. Mutation Res. 142:127-131 https://doi.org/10.1016/0165-7992(85)90052-1
  14. Sparnins, V.L., Barany, G., and Wattenberg, L.W. (1988)Effects of organicsulfur compounds from galic and onions onbenzo(a)Pyreneinduced neoplasia and glutathione S-transfe-rase activity in the mouse. Carcinosenesis. 9: 131-134 https://doi.org/10.1093/carcin/9.1.131
  15. Wattenberg, L.W., Sparnins, V.L., and Barany, G. (1989)Inhibition of N-nitrosodiethylamine carcinogenesis in miceby naturally occurring organosulfur compounds and monoterpenes. Cancer Res. 49: 2689-2692
  16. Pan, J., Hong, J.-Y., Li, D., Schuetz, E.G., Guzelian, P.S.,Huang, W., and Yang, C.S. (1993) Regulation of cytochromeP4502B1/2 genes by dially sulfide, disulfiram, and otherorganosulfur compounds in primary cultures of rathepatocytes. Biochem. Pharmacol. 45: 2323-2329 https://doi.org/10.1016/0006-2952(93)90206-C
  17. Wei, M., Tye, L,, Bickers, D.R., and Brit, D.F. (1990)Inhibitory effect of apigenin, a plant flavonoid, on epidermalomithine decaboxylase and skin tumor promotion in mice.Cancer Res. 50: 499-502
  18. Wang, Z.Y., Cheng, S.J., Zhou, Z.C., Athar, M., Khan, W.A.,Bickers, D.R., and Mukhtar, H. (1989a) Antimytagenic activity of green tea polyphenols. Mutat. res. 223: 273-285 https://doi.org/10.1016/0165-1218(89)90120-1
  19. Wang, Z.Y., Khan, W.A., Bickers, D.R., and Mukhtar, H.(1989b) Protection against polycyclic hydrocarbon-inducedskin tumor initiation in mice by green tea polyphenols.Carcinogenesis. 10: 411-415 https://doi.org/10.1093/carcin/10.2.411
  20. Sakai, Y., Nagas, H., Ose, Y., Sato, T., Yamada, A., Hibi, M.,and Yamada, F. (1989) Antimutagenicity of extract fromcrude drugs in Chinese medicines. Mutat. Res. 174: 1-5 https://doi.org/10.1016/0165-7992(86)90068-0
  21. Mukhtar, H., Das, M., Khan, W.A., Wang, Z.Y., Bik, D.P.,Bickers, D.R. (1988) Exceptional activity of tanic acidamong naturally accuring plant phenols in protection againstDMBA, BP, 3-Mc and N-methyl-N-nitrosourea-induced skintumorigenesis in mice. Cancer Res. 48: 2631-2635
  22. Burke, M.D., Thompson, S., Weaver, R.J., Wolf, C.R., andMayer, R.T. (1994) Cytochrome P450 specificities of alkoxy-resorufin O-dealkylation in human and rat liver. Pharmacol.48: 923-936
  23. Dicker, E., McHugh, T., and Cederbaum, A.I. (1990)Increased oxidation of p-nitrophenol and aniline by intacthepatocytes isolated from pyrazole-treated rats. Biochem.Biophys. Acta. 1035: 249-256 https://doi.org/10.1016/0304-4165(90)90086-C
  24. Lowry, O.H., Rosenbrough, N.J., Farr, A.L., and Randall,R.J. (1951) Protein measurement with the folin phenolreagent. J. Biol. Chem. 193: 265-275