In the present study, the potential
antioxidant and anti-inflammatory effects of Acanthopanax divaricatus vat. albeofructus (AE) and
acanthoside-D (AD) isolated from AE against hepatic
ischemia-reperfusion (I/R) injury were investigated in a rat model. Male Sprague-Dawley rats (200-220 g) were randomized into seven groups: normal controls;
sham-operated controls; I/R injury model; I/R injury model with AE pretreatment at 150, 300, and 600 mg/kg
body weight; and I/R injury model with AD pretreatment at 600 μg/kg
body weight (equivalent to high dose of AE). The AE and AD pretreatments were administered orally for 2 weeks prior to I/R injury surgery. All rats recovered for 1 week with AE and AD treatment after surgery. Compared to the normal control groups, the I/R injury model group without supplemental treatment showed a significantly lower level of serum
superoxide dismutase (SOD) and significantly higher levels of
tumor necrosis factor-alpha (TNF-α,
interleukin (IL)-6, serum
aspartate aminotransferase (AST),
alanine aminotransferase (ALT), and
alkaline phosphatase (ALP), as well as
lactate dehydrogenase (LDH) activity. The I/R-induced decrease in SOD and increases in TNF-α and IL-6 were resolved, at least partially, by AE and AD treatments, as evidenced by significantly higher
antioxidant activities and significantly lower inflammatory
cytokine levels in the treatment groups as compared to the I/R injury model group. The AE and AD treatment groups also showed significantly higher levels of serum IL-10 than I/R injury model group. Histological examination revealed that the AE and AD treated groups had less extensive liver
necrosis than I/R injury model group. Concomitantly, AE lowered the I/R-induced increases in AST, ALT, ALP levels and LDH activity. In conclusion, AE and AD are capable of alleviating I/R-induced hepatic injury by inhibiting inflammatory cell infiltration, thereby mitigating the release of inflammatory
cytokines and balancing the
oxidant-
antioxidant status mediated by
p38 MAPK and JNK/SAPK signaling.