LAUSR

Simple Summary Acetaminophen overdose causes acute liver injury by excessive oxidative stress. The present study examines the mechanisms underlying the protective effect of corilagin against acetaminophen-induced liver injury. Our results showed that corilagin attenuates the liver injury through its anti-oxidant and anti-inflammatory properties. Corilagin may be a therapeutic agent for acute liver injury. Abstract Acetaminophen (APAP) overdose causes acute liver injury via oxidative stress, uncontrolled inflammatory response, and subsequent hepatocyte death. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a potent source of cellular reactive oxygen species (ROS) and may contribute to oxidative stress in many inflammatory processes. Corilagin, a component of Phyllanthus urinaria, possesses antioxidant, anti-inflammatory, and hepatoprotective effects. We evaluated the mechanisms underlying the protective effect of corilagin against acetaminophen-induced liver injury. Mice were intraperitoneally administrated 300 mg/kg APAP or equal volume of saline (control), with or without various concentrations of corilagin (0, 1, 5, or 10 mg/kg) administered after 30 min. All animals were sacrificed 16 h after APAP administration, and serum and liver tissue assays including histology, immunohistochemistry, and Western blot assay were performed. Corilagin post-treatment significantly attenuated APAP-induced liver injury (p < 0.005), inflammatory cell infiltration, hepatic proinflammatory cytokine levels, and hepatic oxidative stress. Furthermore, corilagin attenuated the protein levels of NOX1, NOX2, signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) in APAP-induced liver injury. These results indicated that the antioxidant, anti-inflammatory, and protective effects of corilagin in APAP-induced liver injury might involve the regulation of interleukin (IL)-6/STAT3 and mitogen-activated protein kinase (MAPK)/NF-κB signaling pathways through NOX-derived ROS.