Paeoniflorin protects against liver ischemia/reperfusion injury in mice via inhibiting HMGB1‐TLR4 signaling pathway

Hepatic ischemia/reperfusion (I/R) injury is a major cause of high morbidity and mortality after liver resection, transplantation, and hemorrhagic shock. Paeoniflorin (PF), the main substance of glucosides in Radix Paeoniae Alba , has been widely used to treat various hepatic inflammatory diseases including I/R injury. However, the underlying mechanisms of PF on hepatic I/R injury remain further investigated. In this study, the liver I/R model was performed by clamping the portal vein and hepatic artery with an atraumatic clamp for 90 min followed by 6 hr reperfusion. PF (100 mg/kg) was given three times a day by gavage before I/R. The blood and hepatic samples were collected to evaluate liver injury and molecular indexes. The results showed that PF pretreatment significantly inhibited I/R‐induced serum ALT and AST activities (40.3% and 53.8% those of I/R group, respectively), hepatic pathological damages and hepatic apoptosis ( P <  0.01), and infiltration of neutrophils into liver. In addition, PF suppressed the production of pro‐inflammatory cytokines ( P <  0.01), decreased the expression of high mobility group box‐1 (HMGB1), and down‐regulated toll‐like receptors 4 (TLR4) and phosphorylated ERK1/2, JNK1/2, p38, and NF‐κB signal molecules expression in the I/R‐operated mice. These findings indicated that PF played a protective role in liver I/R injury, and this protection was associated with inhibition of I/R‐activated HMGB1‐TLR4 signaling pathway to attenuate hepatic inflammation responses.