Role of NADPH Oxidase-Derived ROS-Mediated IL-6/STAT3 and MAPK/NF-κB Signaling Pathways in Protective Effect of Corilagin against Acetaminophen-Induced Liver Injury in Mice

• Published in: Biology (Basel, Switzerland) Switzerland), 2023-02, Vol.12 (2), p.334
• Main Authors: Liu, Fu-Chao, Lee, Hung-Chen, Liao, Chia-Chih, Chou, An-Hsun, Yu, Huang-Ping
• Format: Article
• Language: English
• Subjects: Acetaminophen; Analgesics; Anti-inflammatory agents; Antioxidants; Communication; corilagin; CYBB protein; Health aspects; Immunohistochemistry; Inflammation; Interleukin 6; Interleukins; Kinases; Lipid peroxidation; Liver; liver injury; MAP kinase; NAD(P)H oxidase; NADPH-diaphorase; Neutrophils; NF-κB; NF-κB protein; Niacinamide; NOX; Overdose; Oxidants; Oxidases; Oxidative stress; Phosphates; Reactive oxygen species; Signal transduction; Stat3 protein; Tumor necrosis factor-TNF
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology12020334

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 , 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 ( < 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.