Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
권호 표지

Study on the Hepatoprotective Effect and Cytochrome P450 Regulation of Scutellaria Radix

황금의 간세포 보호활성 및 cytochrome P450 발현 조절에 관한 연구

  • Ha, Ki-Tae (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Jeong, Sang-Sin (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Kim, Cheorl-Ho (Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sungkyunkwan University) ;
  • Choi, Dall-Yeong (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Kim, June-Ki (Department of Pathology, College of Oriental Medicine, Dongguk University)
  • 하기태 (동국대학교 한의과대학 병리학교실) ;
  • 정상신 (동국대학교 한의과대학 병리학교실) ;
  • 김철호 (성균관대학교 자연과학부 생명과학과) ;
  • 최달영 (동국대학교 한의과대학 병리학교실) ;
  • 김준기 (동국대학교 한의과대학 병리학교실)
  • Published : 2008.02.25
Download PDF
⟨ Previous Next ⟩

Abstract

Carbon tetrachloride $(CCl_4)-induced$ liver injury depends on a toxic agent that has to be metabolized by the liver NAPDH-cytochrome P450 enzyme system to a highly reactive intermediate. Although several isoforms of cytochrome P450 may metabolize $CC1_4$, attention has been focused largely on the cytochrome P450 2E1 (CYP2E1), which is ethanol-inducible. Alternations in the activity of CYP2E1 affect the susceptibility to hepatic injury from $CC1_4$. In this study, the liver protective effect of the hot water extracts of Scutellaria radix (SR) was investigated. The SR exhibited a hepatoprotective activity against $CCl_4-induced$ liver damage in Chang liver cells. The expression of CYP2E1, measured by RT-PCR and Western blot analysis, was significantly decreased by SR treatment in Chang cells. Based on these findings, it is suggested that hepatoprotective effect of SR possibly related to downregulation of CYP2E1 expression.

Keywords

References

  1. 조병권. 사염화탄소 투여로 인한 血淸內 各種酵素의 活性變動에 關하여. 경북대학교 대학원 박사학위논문, 1984
  2. 서혜진. 사염화탄소의 반복투여가 백서 간장에 미치는 병리조직학적 연구, 영남대학교 대학원 석사학위논문, 1987
  3. Fernandez, G., Villarruel, M.C., de Toranzo, E.G., Castro, J.A. Covalent binding of carbon tetrachloride metabolites to the heme moiety of cytochrome P-450 and its degradation products. Res. Commun. Chem. Pathol. Pharmacol. 35(2):283-290, 1982
  4. Tomasi, A., Albano, E., Banni, S., Botti, B., Corongiu, F., Dessi, M.A., Iannone, A., Vannini, V., Dianzani, M.U. Free-radical metabolism of carbon tetrachloride in rat liver mitochondria. A study of the mechanism of activation. Biochem. J. 246(2):313-317, 1987 https://doi.org/10.1042/bj2460313
  5. Le Page, R.N., Cheeseman, K.H., Osman, N., Slater, T.F. Lipid peroxidation in purified plasma membrane fractions of rat liver in relation to the hepatoxicity of carbon tetrachloride. Cell. Biochem. Funct. 6(2):87-99, 1988 https://doi.org/10.1002/cbf.290060203
  6. Srivastava, S.P., Chen, N.Q., Holtzman, J.L. The in vitro NADPH-dependent inhibition by $CCl_4$ of the ATP-dependent calcium uptake of hepatic microsomes from male rats. Studies on the mechanism of the inactivation of the hepatic microsomal calcium pump by the CCl3. radical. J. Biol. Chem. 265(15):8392-8399, 1990
  7. 辛民敎. 원색임상본초학. 서울, 남산당, pp 308-309, 1986
  8. 李尙仁. 本草學. 서울, 修書院, pp 501-503, 1991
  9. 小學館. 中藥大辭典. 上海科學技術 出版社, p 132, 1985
  10. Nan, J.X., Park, E.J., Kim, Y.C., Ko, G., Sohn, D.H. Scutellaria baicalensis inhibits liver fibrosis induced by bile duct ligation or carbon tetrachloride in rats. J Pharm Pharmacol 54(4):555-563, 2002 https://doi.org/10.1211/0022357021778673
  11. 김성일, 김갑성, 도원석. 황금약침액의 흰쥐 간세포내의 항산화 효과에 관한 연구. 대한침구학회지 16(1):497-509, 1999
  12. Kim, B.R., Kim, D.H., Park, R., Kwon, K.B., Ryu, D.G., Kim, Y.C., Kim, N..Y, Jeong, S., Kang, B.K., Kim, K.S. Effect of an extract of the root of Scutellaria baicalensis and its flavonoids on aflatoxin B1 oxidizing cytochrome P450 enzymes. Planta Med 67(5):396-399, 2001 https://doi.org/10.1055/s-2001-15810
  13. Reitman, S. and Frankel, S. A colorimetric method for determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases, Am. J. Clin. Pathol. 28: 58-63, 1957
  14. Poli, G. Liver damage due to free radicals. Br Med Bull. 49(3):604-620, 1993 https://doi.org/10.1093/oxfordjournals.bmb.a072634
  15. Kamokawa, A., Ohta, S., Tatsugi, A., Kumasaka, M., and Shinoda, M. Experimental Production of Various Types of Cholestasis and the Effects of Cystemine. YAKUGAKU ZASSHI. 106(8):709, 1986 https://doi.org/10.1248/yakushi1947.106.8_709
  16. Noguchi, T., Fong, K.L., Lai, E.K., Olson, L. and McCay, P.B. Selective early loss of polypeptides in liver microsomes of $CCl_4-treated$ rats. Relationship to cytochrome P-450 content. Biochem. Pharmacol. 31(5):609-614, 1982 https://doi.org/10.1016/0006-2952(82)90439-7
  17. Weddle, C.C., Hornbrook, K.R. and McCay, P.B. Lipid peroxidation and alteration of membrane lipids in isolated hepatocytes exposed to carbon tetrachloride. J. Biol. Chem. 251(16):4973-4978, 1976
  18. Clawson, G.A., Sesno, J., Milam, K., Wang, Y.F., Gabriel, C. The hepatocyte protein synthesis defect induced by galactosamine involves hypomethylation of ribosomal RNA. Hepatology. 11(3):428-434, 1990 https://doi.org/10.1002/hep.1840110314
  19. Watanabe, A., Akamatsu, K., Takesue, A., Taketa, K. Dysregulation of protein synthesis in injured liver. A comparative study on microsomal and cytosole enzyme activities, microsomal lipoperoxidation and polysomal pattern in D-galactosamine and carbon tetrachloride-injured livers. Enzyme. 23(5):320-327, 1978 https://doi.org/10.1159/000458596
  20. Poli, G., Chiarpotto, E., Albano, E., Cottalasso, D., Nanni, G., Marinari, U.M., Bassi, A.M., Dianzani, M.U. Carbon tetrachloride-induced inhibition of hepatocyte lipoprotein secretion: functional impairment of Golgi apparatus in the early phases of such injury. Life Sci. 36(6):533-539, 1985 https://doi.org/10.1016/0024-3205(85)90634-4
  21. Biasi, F., Albano, E., Chiarpotto, E., Corongiu, F.P., Pronzato, M.A., Marinari, U.M., Parola, M., Dianzani, M.U., Poli, G. In vivo and in vitro evidence concerning the role of lipid peroxidation in the mechanism of hepatocyte death due to carbon tetrachloride. Cell Biochem Funct. 9(2):111-118, 1991 https://doi.org/10.1002/cbf.290090208
  22. 崔達永, 金俊錡. 傷寒論釋講. 서울, 大星文化社, p 149, 163, 1998
  23. 許浚. 東醫寶鑑. 서울, 南山堂, pp 512-515, 971, 1992
  24. 陳存仁. 圖說漢方醫藥大辭典(I). 東京, 講談社, p 146, 1982
  25. Kim, J.Y., Lee, S., Kim, D.H., Kim, B.R., Park, R., Lee, B.M. Effects of flavonoids isolated from Scutellariae radix on cytochrome P-450 activities in human liver microsomes. J Toxicol Environ Health A. 65(5-6):373-381, 2002 https://doi.org/10.1080/15287390252808046
  26. Gwebu, E.T., Ttewyn, R.W., Cornwell, D.G. and Panganamala, R.V. Vitamin E and inhibition of platelet lipoxygenase. Res. Common. Chem. Pathol. Pharmacol. 28: 361-369, 1980
  27. Rogers, J.F., Nafziger, A.N., Bertino, J.S. Jr. Pharmacogenetics affects dosing, efficacy, and toxicity of cytochrome P450- metabolized drugs. Am J Med. Dec 15;113(9):746-750, 2002
  28. Koop, D.R. Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J. 6(2):724-730, 1992 https://doi.org/10.1096/fasebj.6.2.1537462
  29. Degawa, M., Mikami, K., Namiki, M., Hashimoto, Y. Inhibition of the induction and activity of hepatic P450IA isozymes by in vivo administration of carbon tetrachloride to rats. Biol Pharm Bull. 16(12):1248-1250, 1993 https://doi.org/10.1248/bpb.16.1248
  30. Ronis, M.J., Ingelman-Sundberg, M., Badger, T.M. Induction, suppression and inhibition of multiple hepatic cytochrome P450 isozymes in the male rat and bobwhite quail (Colinus virginianus) by ergosterol biosynthesis inhibiting fungicides (EBIFs). Biochem Pharmacol. 16, 48(10):1953-1965, 1994 https://doi.org/10.1016/0006-2952(94)90594-0
  31. Wong, F.W., Chan, W.Y., Lee, S.S. Resistance to carbon tetrachloride-induced hepatotoxicity in mice which lack CYP2E1 expression. Toxicol Appl Pharmacol. 153(1):109-118, 1998 https://doi.org/10.1006/taap.1998.8547