생약학회지 (Korean Journal of Pharmacognosy)

한국생약학회 (The Korean Society of Pharmacognosy)
권호 표지

마늘의 약물대사효소 CYP3A4 저해 활성

Inhibiting Activity of Garlic on a Drug Metabolizing Enzyme CYP3A4

  • 이은희 (상지대학교 바이오산업공학과) ;
  • 차배천 (상지대학교 바이오산업공학과)
  • Lee, Eun-Hee (Department of Bio-Industry and Technology, Sangji University) ;
  • Cha, Bae-Cheon (Department of Bio-Industry and Technology, Sangji University)
  • 발행 : 2006.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Garlic(Allium sativum Linn) is widely used as a common condiment for a variety of foods and beverages. It has been well known that fresh garlic and garlic supplement of commercial preparations have various therapeutic properties including antimicrobial activity, antiplatelet aggregation, antihypertension, and cholesterol-lowering effects, which contribute to its increasing uses for an alternative medicine. Allicin(diallyl thiosulfinate), the major bioactive components of garlic, is formed by alliinase cleavage of the naturally occurring alliin upon crushing or mincing of garlic, and is the progenitor of a number of other products, such as diallyl disulfide. CYP3A4, heme-containing monooxygenase, is a key enzyme responsible for drug metabolism. Therefor, in the present study, we isolated and examined the compounds with CYP3A4-inhibiting activities from garlic. Among EtOAc extracts of garlic, we found that N-p-coumaroyltyramine and N-feruloyltyramine showed remarkable CYP3A4-inhibiting activities, compared to diallyl disulfide. Structures of the isolated active compounds were established by chemical and spectroscopic means.

키워드

참고문헌

  1. 武政三男 (1981) スパイス百科事典, p. 173-177. 三珠書房, 東京, 日本
  2. Kamanna,V. S. and Chandrasekhara, N. (1983) Biochemical and physiological effects of garlic(Allium sativum Linn). J. Sci. Industr. Res. 42: 353-357
  3. Cavallito, C.J., Bailey, J.H. and Buck, J.S. (1976) The antibacterial principle of Allium sativum III. Its precursor and essential oil garlic. J. Am. Chern. Soc. 67: 1032-1037
  4. Yu, T.H., Wu, C.M. and Kioy, Y.C. (1989) Volatile compounds from garlic. J. Agric. Food Chem. 37: 725-730 https://doi.org/10.1021/jf00087a032
  5. Kato, R., Chiesara, E. and Vassanelli, P. (1964) Further studies on the inhibition and stimulation of microsomal drug metabolizing enzymes of rat liver by various compounds. Biochem. Pharmacal. 13: 69-83 https://doi.org/10.1016/0006-2952(64)90080-2
  6. Conney, A.H. (1967) Pharmacological implication of microsomal enzyme induction. Pharmacal. Rev. 19: 317-366
  7. Neter, K.J. (1980) Inhibitionof oxidativedrug metabolism in microsomes. Pharm Ther. 10: 515-535 https://doi.org/10.1016/0163-7258(80)90029-7
  8. Wrighton, S.A. and Ring, B.J. (1992) Inhibition of human CYP3A4 catalyzed I'-hydroxy midazolam formation by ketoconazole, bifedipine, erythromycin cimetidine, and nizatidine. Pharm. Res. 11: 921-924 https://doi.org/10.1023/A:1018906614320
  9. Cantoni, L., Valaperta, R., Ponsoda, X., Castell, J.V., Barelli, D., Rizzardini, M., Mangolini, A, Hauri, L. and Villa, P. (2003) Induction ofhepatic heme oxygenase-1 by diclofenac in rodents: role of oxidative stress and cytochrome P-450 activity. J. Hepatol. 38: 776-783 https://doi.org/10.1016/S0168-8278(03)00095-3
  10. Nelson, D.R., Koymans, L., Kamataki, T., Stegeman, J.J., Feyereisen, R., Waterman, M.R., Gotoh, O., Coon, M,J., Estabrook, R.W., Gunsalus, I.C. and Nebert, D.W. (1996) P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6: 1-42 https://doi.org/10.1097/00008571-199602000-00002
  11. Guengerich, F.P. (1997) Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chemico-Biological Interactions 106: 161-182 https://doi.org/10.1016/S0009-2797(97)00068-9
  12. Shimada, T.,Tamazaki, H., Mimura, M., Inui, Y. and Guengerich, F.P. (1994) Interindividual variations in human liver cytochrome P450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals : studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Parmacol. Exp. Ther. 270: 414-423;
  13. Williams, M.L., Lennard, M.S., Martin, I.J. and Tucker, G.T. (1994) Interindividual variation in the isomerization of 4hydroxytamoxifen by human liver microsomes : involvement of cytochrome P450. Carcinogenesis. 15: 2733-2738 https://doi.org/10.1093/carcin/15.12.2733
  14. Moltke, L.L., Greenblatt, D.J., Cotreau-Bibbo, M.M., Harmatz, J.S. and Shader, R.I. (1994) Inhibitors of alprazolam metabolism in effect of serotonin- reuptake-inhibitor antidepressants, ketoconazole and quinidine. Br. J. Clin. Pharmacol. 38: 23-31 https://doi.org/10.1111/j.1365-2125.1994.tb04317.x
  15. Granberg, A.L., Brunstrom, B. and Brandt, I. (2000) Cytochrome P450-dependent binding of 7,12-dimethylbenz[a] anthracene(DMBA) and benzo[a] pyrene (B[a]P) in murine heart, lung, and liver endothelial cells. Arch. Toxicol. 74: 593-601 https://doi.org/10.1007/s002040000171
  16. Rushmore, T.H. and Kong, A.N. (2002) Phamacogenomics, regulation and signaling pathways ofphase and drug metabolizing enzyme. Curr. Drug Metab. 3: 481-490 https://doi.org/10.2174/1389200023337171
  17. Yee, G.C., Stanley, D.L., Pessa, L.J., Dalla, C.T., Belz, S.E., Ruiz, J. and Lowenthal, D.T. (1995) Effect ofgrapefruit juice on blood cyclosporin concentration. Lancet. 345: 955-956 https://doi.org/10.1016/S0140-6736(95)90700-9
  18. Henderson, M.C., Miranda, C.L., Stevens, J.F., Deinzer, M.L. and Buhler, D.R. (2000) In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops. Humulus lupuIus. Xenobiotica. 30: 235-251 https://doi.org/10.1080/004982500237631
  19. Tsunoda, S.M., Harris, R.Z., Christians, U., Velez, R.L., Freeman, R.B., Benet, L.Z. and Warshaw, A. (2001) Red wine decreases cyclosporine bioavailability. Clin. Pharmacol. Ther. 70: 462-467
  20. Dresser, G.K., Wacher, V., Wong, S., Wong, H.T. and Bailey, D.G. (2002) Evaluation of peppermint oil and ascorbyl palmitate as inhibitors of cytochrome P450 3A4 activity in vitro and in vivo. Clin. Pharmacol. Ther. 72: 247-255 https://doi.org/10.1067/mcp.2002.126409
  21. Cha, B.C. (2003) Inhibitory effect of a drug metabolizing enzyme CYP3A4 on spices. Kor. J. Pharmacogn. 34: 86-90
  22. Chen, C.Y., Chang, F.R., Yen, H.F. and Wu, Y.C. (1998) Amides from stems of Annona cherimola. Phytochemistry. 49: 1443-1447 https://doi.org/10.1016/S0031-9422(98)00123-X
  23. Park, J.B. and Schoene, N. (2000) Synthesis and characterization of N-p-coumaroyltyramine as a potent phytochemical which arrests human transformed cells via inhibiting protein tyrosine kinases. Biochem. Biophys. Res. Commun. 292: 1104-1110
  24. Fukuda, N., Yonemitsu,M. and Kimura, T. (1983) Studies on the constituents of the stems of Tinospora tuberculata Beumee. I. N-trans- and N-cis-feruloyl tyramine and a new phenolic glucoside tinotuberide. Chem. Pharm. Bull. 31: 156-161 https://doi.org/10.1248/cpb.31.156
  25. Gregory P., Patrice, A.M., Jennifer, G., Norman, G.L. and Clarence,A.R. (1998) Accumulation offeruloyltyramine and p-coumaroyltyramine in tomato leaves in response to wounding. Phytochemistry 47: 659-664 https://doi.org/10.1016/S0031-9422(97)00620-1
  26. Yamamoto, I., Matsunaga, T., Kobayashi, H., Watanabe, K. and Yoshimura, H. (1991) Analysis and pharmacotoxicity of feruloyl tyramine as a new constituent and p-coumaroyltyramine in Cannabissativa L. Pharmacol. Biochem. Behavior 40: 465-469 https://doi.org/10.1016/0091-3057(91)90348-6
  27. Jalifah, L., Thomas, G.H. and Peter, G.W. (1999) Lignans and coumarins metabolites from Melicope hayesii. Phytochemistry 51: 107-110 https://doi.org/10.1016/S0031-9422(98)00720-1
  28. Yoo, I.D., Lee, I.K., Yoo, I.J., Choung, D.H., Han, K.H. and Yun, B.S. (1997) Studies on the constituents of Hibiscus syriacus (I). Kor. J. Pharmacogn. 28: 112-116
  29. Sarker, S.D., Bartholomew, B. and Nash, R.J. (2000) Alkaloids from Balanites aegyptiaca. Fitoterapia. 71: 328-330 https://doi.org/10.1016/S0367-326X(99)00149-5
  30. King, R.R. and Calhoun, L.A. (2005) Characterization of cross-linked hydroxy cinnamic acid amides isolated from potato common scab lesions. Phytochemistry 66: 2468-2473 https://doi.org/10.1016/j.phytochem.2005.07.014