Alaternin and emodin with hydroxyl radical inhibitory and/or scavenging activities and hepatoprotective activity on tacrine-induced cytotoxicity in HepG2 cells

Arch Pharm Res. 2004 Sep;27(9):947-53. doi: 10.1007/BF02975849.

Abstract

The antioxidative and hepatoprotective potentials of two anthraquinones, alaternin (2-hydroxyemodin) and emodin, to scavenge and/or inhibit hydroxyl radicals generated by the Fenton reaction and to protect tacrine-induced cytotoxicity in human liver derived HepG2 cells were evaluated, respectively. The inhibitory activity on hydroxyl radical generated in a cell-free chemical system (FeSO4/H2O2) was investigated by a fluorescence spectrophotometer using a highly fluorescent probe, 2',7'-dichlorofluorescein. The hydroxyl radical scavenging activity was determined by electron spin resonance spectroscopy using 5,5-dimethy-1-pyrroline-N-oxide as hydroxyl radicals trapping agents. Tacrine-induced HepG2 cell toxicity was determined by a 3-[4,5-dimethylthiazole-2yl]-2,5-diphenyltertrazolium bromide assay. Although the scavenging activity of alaternin on hydroxyl radical was similar to that of emodin in dose-dependent patterns, the inhibitory activity exhibited by the former on hydroxyl radical generation was stronger than that of the latter, with IC50 values of 3.05 +/- 0.26 microM and 13.29 +/- 3.20 microM, respectively. In addition, the two anthraquinones, alaternin and emodin showed their hepatoprotective activities on tacrine-induced cytotoxicity, and the EC50 values were 4.02 microM and 2.37 microM, respectively. Silymarin, an antihepatotoxic agent used as a positive control exhibited the EC50 value of 2.00 microM. These results demonstrated that both alaternin and emodin had the simultaneous antioxidant and hepatoprotective activities.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Emodin / analogs & derivatives*
  • Emodin / chemistry
  • Emodin / pharmacology*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Humans
  • Hydroxyl Radical / antagonists & inhibitors*
  • Hydroxyl Radical / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Tacrine / toxicity*

Substances

  • Free Radical Scavengers
  • Hydroxyl Radical
  • Tacrine
  • 2-hydroxyemodin
  • Emodin