Hepatoprotective compounds of Cassiae Semen on tacrine-induced cytotoxicity in Hep G2 cells

결명자의 타크린으로 유발한 간 세포독성 보호 성분

  • Byun, Erisa (College of Pharmacy, Wonkwang University) ;
  • Jeong, Gil-Saeng (Institute for Radiological Imaging Science, Wonkwang University) ;
  • An, Ren-Bo (College of Pharmacy, Yanbian University) ;
  • Li, Bin (College of Pharmacy, Wonkwang University) ;
  • Lee, Dong-Sung (College of Pharmacy, Wonkwang University) ;
  • Ko, Eun-Kyung (College of Pharmacy, Wonkwang University) ;
  • Yoon, Kwon-Ha (Institute for Radiological Imaging Science, Wonkwang University) ;
  • Kim, Youn-Chul (College of Pharmacy, Wonkwang University)
  • 변에리사 (원광대학교 약학대학) ;
  • 정길생 (원광대학교 익산방사선연구센터) ;
  • 안인파 (연변대학교 약학대학) ;
  • 리빈 (원광대학교 약학대학) ;
  • 이동성 (원광대학교 약학대학) ;
  • 고은경 (원광대학교 약학대학) ;
  • 윤권하 (원광대학교 익산방사선연구센터) ;
  • 김윤철 (원광대학교 약학대학)
  • Published : 2007.12.31

Abstract

Tacrine is an acetylcholinesterase inhibitor that is approved for the treatment of Alzheimer's disease. However, tacrine treatment for Alzheimer's disease results in reversible hepatotoxicity in 30-50% of patients, which seriously limits its clinical use. Accordingly, the identification of constituents in natural products that have protective effects on tacrine-induced hepatotoxicity would be valuable. In the present study, an immortalized human hepatoma cell line, HepG2 was employed to screen for agents that protect against tacrine-induced hepatotoxicity. The bioassay-guided fractionation of water extract of Cassiae Semen furnished two anthraquinones, aurantio-obtusin (1) and obtusifolin (2). Compounds 1 and 2 showed hepatoprotective effects with the protection ratio values of 55.3 +/- 0.5% and 41.2 +/- 0.8% at $160{\mu}M$, respectively.

Keywords

References

  1. Jim, L. K. and Gee, J. P. (1995) Adverse effects of drugs on the liver. In Young, L. Y and Koda-Kimble, M. A. (ed.), Applied therapeutics: The clinical use of drugs, 26-1-26-17, Applied Therapeutics, Inc., Vancouver
  2. Watkins, P. B., Zimmermann, H. J., Knapp, M. J., Gracon, S. I. and Lewis, K. W. (1994) Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. J. Am. Med. Assoc. 271: 992-998 https://doi.org/10.1001/jama.271.13.992
  3. Grant, M. H., Duthie, S. J., Gray, A. G. and Burke, M. D. (1988) Mixed function oxidase and UDP-glucuronyltransferase activities in the human Hep G2 hepatoma cell line. Biochem. Pharmacol. 37: 4111-4116 https://doi.org/10.1016/0006-2952(88)90103-7
  4. Viau, C. J., Curren, R. D. and Wallace, K. (1993) Cytotoxicity of tacrine and velnacrine metabolites in cultured rat, dog, and human hepatocytes. Drug Chem. Toxicol. 16: 227-239 https://doi.org/10.3109/01480549309081817
  5. 정보섭, 신민교 (1998) 도해 향약(생약)대사전(식물편), 813-814. 도서출판 영림사, 서울
  6. Yang, Y. C., Lim, M. Y., Baek, Y. I. and Lee, H. S. (2003) Emodin isolated from Cassia obtusifolia (Leguminosae) seed shows larvicidal activity against three mosquito species. J. Agric. Food. Chem. 51: 7629-7631 https://doi.org/10.1021/jf034727t
  7. Wu, C. H. and Yen, G. C. (2004) Antigenotoxic properties of Cassia tea (Cassia tora L.): Mechanism of action and the influence of roasting process. Life. Sci. 76: 85-101 https://doi.org/10.1016/j.lfs.2004.07.011
  8. Kim, Y. M., Lee, C. H., Kim, H. G. and Lee, H. S. (2004) Anthraquinone isolated Cassia tora (Leguminosae) seed show an antifungal property against Phytopathogenic fungi. J. Agric. Food. Chem. 52: 6069-6100
  9. Choi, J. S., Lee, H. J., Park, K. Y., Ha, J. O. and Kang, S. S. (1996) Invitro antimutagenic effects of anthraqunone aglycones and naphthopyrone glycosides from Cassia tora. Planta Med. 63: 11-14 https://doi.org/10.1055/s-2006-957593
  10. Wong, S. M., Wong, M. M., Seligmann, O. and Wagner, H. (1988) New antihepatotoxic naphtha-pyrone glycosides from the seeds of Cassia tora. Planta Med. 55: 276-280 https://doi.org/10.1055/s-2006-962003
  11. Choi, J. S., Jung, J. H., Lee, H. J., and Kang, S. S. (1996) The NMR assignments of anthraquinones from Cassia tora. Arch. Pharmt. Res. 19: 302-306 https://doi.org/10.1007/BF02976245
  12. Youn-Choi, H. S. and Kim, J. H. (1990) Potential inhibitors of platelet aggregation from plant sources, $V.^1$ Anthraquinones from seeds of Cassia obtusifolia and related $compounds^2$. J. Nat. Prod. 53: 630-633 https://doi.org/10.1021/np50069a014
  13. Galisteo, M., Rissel, M., Sergent, O., Chevanne, M., Cillard, J., Guillouzo, A. and Lagadic-Gossmann, D. (2000) Hepatotoxicity of tacrine: occurrence of membrane fluidity alterations without involvement of lipid peroxidation. J. Pharmacol. Exp. Ther. 294: 160-167
  14. Sung, S.H., Lee, E.J., Cho, J.H., Kim, H.S. and Kim, Y.C. (2000) Sauchinone, a lignan from Saururus chinensis, attenuates CCl4-induced toxicity in primary cultures of rat hepatocytes. Biol. Pharm. Bull. 23: 666-668 https://doi.org/10.1248/bpb.23.666