Acanthoic acid from Acanthopanax koreanum protects against liver injury induced by tert-butyl hydroperoxide or carbon tetrachloride in vitro and in vivo

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Title
Acanthoic acid from Acanthopanax koreanum protects against liver injury induced by tert-butyl hydroperoxide or carbon tetrachloride in vitro and in vivo
Author(s)
E J Park; Y Z Zhao; Y H Kim; Jung Joon Lee; D H Sohn
Bibliographic Citation
Planta Medica, vol. 70, no. 4, pp. 321-327
Publication Year
2004
Abstract
The aim of this study was to investigate the protective effect of acanthoic acid, a diterpene isolated from the root bark of Acanthopanax koreanum, on liver injury induced by either tert-butyl hydroperoxide (tBH) or carbon tetrachloride in vitro and in vivo. In vitro, the cellular leakage of lactate dehydrogenase (LDH) following treatment with 1.5 mM tBH for 1 h, was significantly inhibited by co-treatment with acanthoic acid (25 and 5 μg/mL) and the ED50 of acanthoic acid was 2.58 μg/mL (8.5 μM). The cellular leakage of LDH following one hour of treatment with 2.5 mM CCl 4 was significantly inhibited by co-treatment with acanthoic acid (25 μg/mL) and the ED50 of acanthoic acid was 4.25 μg/mL (14.1 μM). Co-treatment with acanthoic acid significantly inhibited the generation of intracellular reactive oxygen species (ROS) and intracellular glutathione (GSH) depletion induced by tBH or CCl4. Acanthoic acid pretreatment (100 mg/kg per day for four consecutive days, p. o.) significantly reduced levels of aspartate transaminase and alanine transaminase in acute liver injury models induced by either tBH or carbon tetrachloride. Treatment with acanthoic acid (100 mg/kg, p. o.) at 6, 24, and 48 hours after carbon tetrachloride subcutaneous injection significantly reduced the levels of aspartate transaminase and alanine transaminase in serum. Histological observations revealed that fatty acid changes, hepatocyte necrosis and inflammatory cell infiltration in CCl4-injured liver were improved upon treatment with acanthoic acid. In vivo treatment with acanthoic acid was not able to modify CYP2E1 activity and protein expression in liver microsomes at the dose used, showing that the hepatoprotective effect of acanthoic acid was not mediated through inhibition of CCl4 bioactivation. From the results above, acanthoic acid had a protective effect against tBH- or CCl4-induced hepatotoxicity in vitro and in vivo.
Keyword
Acanthoic acidAcanthopanax koreanumAraliaceaeCarbon tetrachlorideHepatoprotective effectTert-butyl hydroperoxide
ISSN
0032-0943
Publisher
Georg Thieme Verlag Kg
DOI
http://dx.doi.org/10.1055/s-2004-818943
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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