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 microg/mL) and the ED (50) of
acanthoic acid was 2.58 microg/mL (8.5 microM). 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 microg/mL) and the ED (50) of
acanthoic acid was 4.25 microg/mL (14.1 microM). Co-treatment with
acanthoic acid significantly inhibited the generation of intracellular
reactive oxygen species (ROS) and intracellular
glutathione (GSH) depletion induced by tBH or CCl (4).
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 CCl (4)-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 CCl (4) bioactivation. From the results above,
acanthoic acid had a protective effect against tBH- or CCl (4)-induced hepatotoxicity in vitro and in vivo.