Protective effects of Acanthopanax divaricatus vat. albeofructus and its active compound on ischemia–reperfusion injury of rat liver

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.

► This study investigated the protective effects of Acanthopanax divaricatus vat. albeofructus (AE). ► AE attenuated inflammatory cell infiltration and extensive necrosis in liver I/R injury rat. ► AE was found to balance the antioxidant status better than acanthoside-D (AD) isolated from AE. ► AE and AD lowered inflammatory cytokine release mediated by JNK/SAPK signaling.