Korean Journal of Pharmacognosy (생약학회지)

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지

Hepatoprotective Activities of Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin

Curcumin, demethoxycurcumin 및 bisdemethoxycurcumin의 간보호 작용

  • Cheon, Ho-Jun (College of Pharmacy, Sungkyunkwan University) ;
  • Park, Jin-Goo (College of Pharmacy, Sungkyunkwan University) ;
  • Kim, Yeong-Shik (College of Pharmacy, Seoul National University) ;
  • Kang, Sam-Sik (College of Pharmacy, Seoul National University) ;
  • Chi, Xing-Fu (Anticancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Jung-Joon (Anticancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Sun-Mee (College of Pharmacy, Sungkyunkwan University)
  • 천호준 (성균관대학교 약학대학) ;
  • 박진구 (성균관대학교 약학대학) ;
  • 김영식 (서울대학교 약학대학) ;
  • 강삼식 (서울대학교 약학대학) ;
  • 채흥복 (한국생명공학연구원 항암물질연구실) ;
  • 이정준 (한국생명공학연구원 항암물질연구실) ;
  • 이선미 (성균관대학교 약학대학)
  • Published : 2007.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The aim of this study was to investigate the protective activity of curcumin, demethoxycurcumin and bisdemethoxycurcumin, isolated from Curcuma longa Linne, on hepatocyte injury induced by carbon tetrachloride (CCl$_4$,10 mM), t-butyl hydroperoxide (TBH, 0.5 mM) and D-galactosamine (GaIN,30 mM). Primary cultures of rat hepatocyte (18 h culture) were treated with CCl$_4$, TBH or GaIN and various concentrations (0.1, 1, 10 and 100 ${\mu}$M) of curcumin, demethoxycurcumin and bisdemethoxycurcumin CCl$_4$ significantly increased the levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The increases in LDH, ALT and AST levels were inhibited by curcumin. Demethoxycurcumin and bisdemethoxycurcumin decreased the levels of AST. Curcumin inhibited the increases in ALT and AST levels induced by TBH. The increased levels of LDH, ALT and AST induced by TBH were inhibited by bisdemethoxycurcumin. GaIN markedly increased the levels of LDH, ALT and AST. These increases were significantly inhibited by bisdemethoxycurcumin. The increase in AST level was inhibited by curcumin. These results suggest that curcumin and bisdemethoxycurcumin have potent hepatoprotective activities.

Keywords

References

  1. 생약학 교재 편찬위원회(2003) 생약학, 419. 동명사, 서울
  2. Khopde, S. M., Priyadarsini, K. I., Venkatesan, P. and Rao, M. N. (1999) Free radical scavenging ability and antioxidant efficiency of curcumin and its substituted analogue. Biophys. Chem. 80: 85-91 https://doi.org/10.1016/S0301-4622(99)00070-8
  3. Balasubramanyam, M., Koteswari, A. A., kumar, R. S., Monickaraj, S. F., Maheswari, J. U. and Mohan, V. (2003) China-English Manual of common-used in traditional Chinenese Medicine. J. Biosci. 28: 715-721 https://doi.org/10.1007/BF02708432
  4. Naik, R. S., mujumdar, A. M. and Ghaskadbi, S. (2004) Protection of liver cells from ethanol cytotoxicity by curcumin in liver slice culture in vitro. J. Ethnopharmacol. 95: 31-37 https://doi.org/10.1016/j.jep.2004.06.032
  5. Pari, L. and Murugan, P. (2004) Protective role of tetrahy-drocurcumin against erythromycin estolate-induced hepatotoxicity. Protective role of tetrahydrocurcumin against erythromycin estolate-induced hepatotoxicity. Pharmacol. Res. 49: 481-486 https://doi.org/10.1016/j.phrs.2003.11.005
  6. Somparn, P., Phisalaphonq, C., Nakornchai, S., Unchern, S. and morales, N. P. (2007) Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol. Pharm. Bull. 30: 74-78 https://doi.org/10.1248/bpb.30.74
  7. Suzuki, M., Nakamura, T., Iyoki, S., Fujiwara, A., Watanabe, Y., Mohri, K., Isobe, K. and Yano, S. (2005) Elucidation of anti-allergic activities of curcumin-related compounds with a special reference to their anti-oxidative activities. Biol. Pharm. Bull. 28: 1438-1443 https://doi.org/10.1248/bpb.28.1438
  8. Chan, W. H., Wu, H. J. and Hsuuw, Y. D. (2005) Curcumin inhibits ROS formation and apoptosis in methylglyoxaltreated human hepatoma G2 cells. Ann. N. Y. Acad. Sci. 1042: 372-378 https://doi.org/10.1196/annals.1338.057
  9. Yoysungnoen, P., Wirachwong, P., Bhattarakosol, P., Niimi, H. and Patumraj, S. (2005) Antiangiogenic activity of curcumin in hepatocellular carcinoma cells implanted nude mice. Clin. Hemorheol. Microcirc. 33: 127-135
  10. Notarbartolo, M., Poma, P., Perri, D., Dusonchet, L., Cervello, M. and D'Alessandro, N. (2005) Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett. 224: 53-65 https://doi.org/10.1016/j.canlet.2004.10.051
  11. Clawson, G. A. (1989) Mechanism of carbon tetrachloride hepatotoxicity. Pathol. Immunopathol. Res. 8: 104-112 https://doi.org/10.1159/000157141
  12. Rush, G. F., Gorski, J. R., Ripple, M. G., Sowinski, J., Bugelski, P. and Hewitt, W. R. (1985) Organic hydroperoxideinduced lipid peroxidation and cell death in isolated hepatocytes. Toxicol. Appl. Pharmacol. 78: 473-483 https://doi.org/10.1016/0041-008X(85)90255-8
  13. Taniguchi, H., Yomota, E., Nogi, K. and Onoda, Y. (2002) Effects of anti-ulcer agents on ethanol-induced gastric mucosal lesions in D-galactosamine-induced hepatitis rats. Arzneimittelforschung. 52: 600-604
  14. Javaprakasha, G. K., Jaqan Mohan Rao, L. and Sakariah, K. K. (2002) Improved HPLC method for the determination of Curcumin, Demethoxycurcumin, and Bisdemethoxycurcumin. J. Agric. Food Chem. 50: 3668-3672 https://doi.org/10.1021/jf025506a
  15. Berry, M. N. and Friend, D. S. (1969) High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J. Cell Biol. 43: 506-520 https://doi.org/10.1083/jcb.43.3.506
  16. Kleinman, H. K., McGoodwin, E. B., Rennard, S. I. and Martin, G. R. (1979) Preparation of collagen substrates for cell attachment: effect of collagen concentration and phosphate buffer. Anal. Biochem. 94: 308-312 https://doi.org/10.1016/0003-2697(79)90365-8
  17. Kiso, Y., Tohkin, M. and Hikino, H. (1983) Assay method for antihepatotoxic activity using carbon tetrachloride induced cytotoxicity in primary cultured hepatocytes. Planta Med. 49: 222-225 https://doi.org/10.1055/s-2007-969855
  18. Tseng, T. H., Wang, C. J., Kao, E. S. and Chu, H. Y. (1996) Hibiscus protocatechuic acid protects against oxidative damage induced by tert-butylhydroperoxide in rat primary hepatocytes. Chem. Biol. Interact. 101: 137-148 https://doi.org/10.1016/0009-2797(96)03721-0
  19. Kiso, Y., Tohkin, M. and Hikino, H. (1983) Assay method for antihepatotoxic activity using galactosamine-induced cytotoxicity in primary-cultured hepatocytes. J. Nat. Prod. 46: 841-847 https://doi.org/10.1021/np50030a003
  20. de Toranzo, E. G., Gomez, M. I. and Castro, J. A. (1978) Carbon tetrachloride activation, lipid peroxidation and liver necrosis in different strains of mice. Res. Commun. Chem. Pathol. Pharmacol. 19: 347-352
  21. Villarruel, M. C., Diaz Gomez, M. I. and Castro, J. A. (1975) The nature of the in vitro irreversible binding of carbon tetrachloride to microsomal lipids. Toxicol. Appl. Pharmacol. 33: 106-114 https://doi.org/10.1016/0041-008X(75)90249-5
  22. Maley, F., Tarentino, A. L., McGarrahan, J. F. and Giacco, R. (1968) The metabolism of D-galactosamine and N-acetyl-Dgalactosamine in rat liver. Biochem. J. 107: 637-644 https://doi.org/10.1042/bj1070637
  23. El-Mofty, S. K., Scrutton, M. C., Serroni, A., Nicolini, C. and Farber, J. L. (1975) Early, reversible plasma membrane injury in galactosamine-induced liver cell death. Am. J. Pathol. 79: 579-595