Alaternin and emodin with hydroxyl radical inhibitory and/or scavenging activities and hepatoprotective activity on tacrine-induced cytotoxicity in HepG2 cells.
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.
Research Institute of Marine Science and Technology, Korea Maritime University, Busan, 606-791, Korea.
Hyun Ah
HA
Jung
Hae Young
HY
Chung
Takako
T
Yokozawa
Youn Chul
YC
Kim
Sook Kyung
SK
Hyun
Jae Sue
JS
Choi
D045744:Cell Line, Tumor; D004642:Emodin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D013619:Tacrine / Q000633:toxicity*
D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D013619:Tacrine; C053054:2-hydroxyemodin; D004642:Emodin