Liver
ischemia-reperfusion injury (IRI) is a common clinical event with high morbidity in patients undergoing complex liver surgery or having abdominal
trauma. Inflammatory and oxidative stress responses are the main contributing factors in liver IRI. The
iridoid glucoside aucubin (AU) has good anti-inflammatory and antioxidative effects; however, there are no relevant reports on the protective effect of
glucosides on hepatic IRI. The purpose of this study was to determine whether AU pretreatment could prevent liver IRI and to explore the mechanism. Sprague-Dawley rats were randomly divided into five groups. The
sham operation and IRI control groups were given
intraperitoneal injections of
normal saline, while the AU low-dose (AU-L) group, AU medium-dose (AU-M) group, and AU high-dose (AU-H) group were given
intraperitoneal injections of AU at doses of 1, 5, and 10 mg/kg/day, respectively. After 10 d, liver IRI (70% liver
ischemia for 1 h, reperfusion for 6 h) was surgically established in all groups except the
sham group. Our results confirmed that liver injury was significantly aggravated after hepatic
ischemia-reperfusion. AU alleviated the increase of
transaminase and pathological changes induced by
ischemia-reperfusion and improved liver damage. AU could also ameliorate the inflammatory and oxidative stress responses induced by
ischemia-reperfusion and reduced expression of high mobility group
protein (HMG)B1,
receptor for advanced glycation end-products (RAGE),
tumor necrosis factor (TNF)-α,
interleukin (IL)-1β, and
reactive oxygen species (ROS). Moreover, AU reduced
ischemia-reperfusion-induced
mitochondrial dysfunction and cells apoptosis, increased
peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and uncoupling (UCP)2
protein expression, and reduced
caspase-3, cleaved
caspase-3, and
Cytochrome P450 proteins (CYP) expression. To determine expression levels of the
Toll-like receptor (TLR)-4/nuclear factor-κB (NF-κB) pathway-related
proteins in vitro and in vivo, we also measured TLR-4, myeloid differentiation factor88 (MyD88), NF-κB P65, p-P65,
I-kappa-B-alpha (IκB-α), and p-IκB-α levels. The results showed that AU effectively inhibited activation of the TLR-4/NF-κB signaling pathway. In conclusion, we showed for the first time a hepatoprotective effect for AU in liver IRI, which acted by inhibiting the
HMGB1/TLR-4/NF-κB signaling pathway, oxidative stress, and apoptosis. Pretreatment with AU may be a promising strategy for preventing liver IRI.