Screening of Herbal Medicines for Recovery of Acetaminophen-induced Hepatotoxicity

  • Sohn, Sung-Hwa (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Lee, Hyo-Eun (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Lee, Beom-Joon (BK21 Oriental Medical Science Center, KyungHee Universityz) ;
  • Kim, Sung-Hoon (Department of Oriental Pathology, College of Oriental Medicine, KyungHee University) ;
  • Shin, Min-Kyu (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Hong, Moo-Chang (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Bae, Hyun-Su (BK21 Oriental Medical Science Center, KyungHee University) ;
  • Kim, Yang-Seok (BK21 Oriental Medical Science Center, KyungHee University)
  • Published : 2008.12.31

Abstract

This study was conducted to quantitatively evaluate the recovery effects of herbal medicines on acetaminophen-induced hepatotoxicity. In the present study, the recovery effects of 251 herbal medicines on THLE-2 cells that had been damaged by acetaminophen were evaluated using an MTS assay. THLE-2 cells were cultured in 96-well plates and then pretreated with or without 60 ${\mu}M$ acetaminophen (${IC}_{50}$ value: 35.84) for 1 hr. Next, different herbal medicines were added to the wells, after which the cells were reincubated at $37^{\circ}C$ for 24 hr. After first round of screening, the candidate herbal medicines were selected based on a recovery rate of greater than 40% and their efficacy were then determined by dose response kinetic analysis. Among these extracts, 8 herbal medicines (Terminalia chebula, Pueraria lobata, Acronychia laurifolia, Lopatherum gracile, Oroxylum indicum, Cynanchum atratum, Senecio scandens, and Sophora flavescens) had a strong recovery effect on acetaminophen-induced damage in THLE-2 cells. Dose response non-linear regression analysis demonstrated that Senecio scandens showed the best recovery rate (98%), and that its ${EC}_{50}$ was 19.54 ng/mL. Additional studies of these herbal medicines should be conducted to determine if they possess novel therapeutic agents for the prevention or treatment of liver disorders.

Keywords

References

  1. Luk, J. M. et al. Traditional chinese herbal medicines for treatment of liver fibrosis and cancer: From laboratory discovery to clinical evaluation. Liver Int 27:879-890 (2007) https://doi.org/10.1111/j.1478-3231.2007.01527.x
  2. Stickel, F. & Schuppan, D. Herbal medicine in the treatment of liver diseases. Dig Liver Dis 39:293-304 (2007) https://doi.org/10.1016/j.dld.2006.11.004
  3. Sohn, J. H., Han, K. L., Choo, J. H. & Hwang, J. K. Macelignan protects hepg2 cells against tert-butylhydroperoxide-induced oxidative damage. Biofactors 29:1-10 (2007) https://doi.org/10.1002/biof.5520290101
  4. Wu, Y., Li, L., Wen, T. & Li, Y. Q. Protective effects of echinacoside on carbon tetrachloride-induced hepatotoxicity in rats. Toxicology 232:50-56 (2007) https://doi.org/10.1016/j.tox.2006.12.013
  5. Yapar, K. et al. Hepatoprotective effect of l-carnitine against acute acetaminophen toxicity in mice. Exp Toxicol Pathol 59(2):121-128 (2007) https://doi.org/10.1016/j.etp.2007.02.009
  6. Sivilotti, M. L., Yarema, M. C., Juurlink, D. N., Good, A. M. & Johnson, D.W. A risk quantification instrument for acute acetaminophen overdose patients treated with n-acetylcysteine. Ann Emerg Med 46:263-271 (2005) https://doi.org/10.1016/j.annemergmed.2005.04.004
  7. Kon, K., Kim, J. S., Jaeschke, H. & Lemasters, J. J. Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes. Hepatology 40:1170-1179 (2004) https://doi.org/10.1002/hep.20437
  8. Devi, K. P., Sreepriya, M., Balakrishna, K. & Devaki, T. Protective effect of premna tomentosa extract (l. Verbanacae) on acetaminophen-induced mitochondrial dysfunction in rats. Mol Cell Biochem 272:171-177 (2005) https://doi.org/10.1007/s11010-005-7142-6
  9. James, L. P., Mayeux, P. R. & Hinson, J. A. Acetaminophen-induced hepatotoxicity. Drug Metab Dispos 31:1499-1506 (2003) https://doi.org/10.1124/dmd.31.12.1499
  10. Jaeschke, H., Knight, T. R. & Bajt, M. L. The role of oxidant stress and reactive nitrogen species in acetaminophen hepatotoxicity. Toxicol Lett 144:279-288 (2003) https://doi.org/10.1016/S0378-4274(03)00239-X
  11. Chung, H. S. et al. Inhibition of nitric oxide and tumor necrosis factor-alpha by moutan cortex in activated mouse peritoneal macrophages. Biol Pharm Bull 30:912-916 (2007) https://doi.org/10.1248/bpb.30.912
  12. Garle, M. J., Fentem, J. H. & Fry, J. R. In vitro cytotoxicity tests for the prediction of acute toxicity in vivo. Toxicology in Vitro 8:1303-1312 (1994) https://doi.org/10.1016/0887-2333(94)90123-6
  13. Zhang, L., Mu, X., Fu, J. & Zhou, Z. In vitro cytotoxicity assay with selected chemicals using human cells to predict target-organ toxicity of liver and kidney. Toxicol In Vitro 21:734-740 (2007) https://doi.org/10.1016/j.tiv.2007.01.013
  14. Liu, F. & Ng, T. B. Antioxidative and free radical scavenging activities of selected medicinal herbs. Life Sci 66:725-735 (2000) https://doi.org/10.1016/S0024-3205(99)00643-8
  15. Tian, X. Y. et al. Jacaranone glycosides from senecio scandens. J Asian Nat Prod Res 8:125-132 (2006) https://doi.org/10.1080/10286020500530912
  16. Li, S. L. et al. Identification of five hepatotoxic pyrrolizidine alkaloids in a commonly used traditional chinese medicinal herb, herba senecionis scandentis (qianliguang). Rapid Commun Mass Spectrom 22:591-602 (2008) https://doi.org/10.1002/rcm.3398
  17. Jung, H. A. et al. Re-evaluation of the antioxidant prenylated flavonoids from the roots of sophora flavescens. Biol Pharm Bull 31:908-915 (2008) https://doi.org/10.1248/bpb.31.908
  18. Liu, Z. et al. A mannose-binding lectin from sophora flavescens induces apoptosis in hela cells. Phytomedicine 15(10):867-875 (2008) https://doi.org/10.1016/j.phymed.2008.02.025
  19. Wang, Y. et al. Purification and preparation of compounds from an extract of scutellaria barbata d. Don using preparative parallel high performance liquid chromatography. J Sep Sci 31:1669-1676 (2008) https://doi.org/10.1002/jssc.200700609