Nobiletin Prevents against Acute Liver Injury via Targeting c-Jun N-terminal Kinase (JNK)-Induced Apoptosis of Hepatocyte.

Acute liver injury resulting from several factors such as medication, food toxin and herbal supplementation, often leads to a severe health condition and difficult treatment, thereby prevention of acute liver injury remains a critical issue and is of great importance. In this study, we investigated the preventive effects of nobiletin (NOB) on a mouse model of concanavalin A (ConA)-induced acute liver injury. We observed that NOB (10 mg/kg) pretreatment of ConA treated mice significantly lowered the levels of liver enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), decreased the intracellular generation of reactive oxygen species (ROS) and suppressed the release of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Pathological data suggested that pretreatment with NOB ameliorated ConA-induced liver damage through promoting proliferation and alleviating apoptosis of hepatocytes. Furthermore, significant suppression of c-Jun activating kinase (JNK) signal was also observed in NOB-pretreated liver tissues compared with that of ConA treatment only. In addition, in vitro mechanism study confirmed that addition of NOB protected hepatocytes via inhibition of JNK activation, manifested that alleviation of JNK-induced apoptosis of hepatocytes is correlated with NOB protection in acute liver injury.