Nobiletin Protects against Acute Liver Injury via Targeting c-Jun N-Terminal Kinase (JNK)-Induced Apoptosis of Hepatocytes.

Acute liver injury resulting from several factors such as medication, food toxins, and herbal supplementation often leads to a severe health condition and makes treatment difficult; thereby, the 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 by promoting proliferation and alleviating apoptosis of hepatocytes. Furthermore, significant suppression of the c-Jun-activating kinase (JNK) signal was also observed in NOB-pretreated liver tissues compared with that of ConA treatment only. In addition, an in vitro mechanism study confirmed that the addition of NOB protected hepatocytes via inhibition of JNK activation, manifesting that alleviation of JNK-induced apoptosis of hepatocytes is correlated with NOB protection in acute liver injury.