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
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 st...
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MDPI AG
2023-02-01
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| author | Fu-Chao Liu Hung-Chen Lee Chia-Chih Liao An-Hsun Chou Huang-Ping Yu |
| author_facet | Fu-Chao Liu Hung-Chen Lee Chia-Chih Liao An-Hsun Chou Huang-Ping Yu |
| author_sort | Fu-Chao Liu |
| collection | DOAJ |
| description | 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 <i>Phyllanthus urinaria</i>, 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 (<i>p</i> < 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. |
| first_indexed | 2024-03-11T09:07:39Z |
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| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T09:07:39Z |
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| series | Biology |
| spelling | doaj.art-07f26bea4a584bd185dcf5e15dfefcc92023-11-16T19:14:59ZengMDPI AGBiology2079-77372023-02-0112233410.3390/biology12020334Role 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 MiceFu-Chao Liu0Hung-Chen Lee1Chia-Chih Liao2An-Hsun Chou3Huang-Ping Yu4Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, TaiwanDepartment of Anesthesiology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, TaiwanDepartment of Anesthesiology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, TaiwanDepartment of Anesthesiology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, TaiwanDepartment of Anesthesiology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, TaiwanAcetaminophen (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 <i>Phyllanthus urinaria</i>, 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 (<i>p</i> < 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.https://www.mdpi.com/2079-7737/12/2/334acetaminophencorilagininflammationliver injuryNOXNF-κB |
| spellingShingle | Fu-Chao Liu Hung-Chen Lee Chia-Chih Liao An-Hsun Chou Huang-Ping Yu 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 Biology acetaminophen corilagin inflammation liver injury NOX NF-κB |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | acetaminophen corilagin inflammation liver injury NOX NF-κB |
| url | https://www.mdpi.com/2079-7737/12/2/334 |
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