scholarly journals c‐Jun NH 2 ‐Terminal Protein Kinase Phosphorylates the Nrf2‐ECH Homology 6 Domain of Nuclear Factor Erythroid 2–Related Factor 2 and Downregulates Cytoprotective Genes in Acetaminophen‐Induced Liver Injury in Mice

Hepatology ◽  
2020 ◽  
Vol 71 (5) ◽  
pp. 1787-1801 ◽  
Author(s):  
Yiping Chen ◽  
Kaihua Liu ◽  
Jingwen Zhang ◽  
Yan Hai ◽  
Peng Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Related Factor ◽  
Nuclear Factor ◽  
Terminal Protein

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2

2018 ◽  
Vol 46 (02) ◽  
pp. 469-488 ◽  
Author(s):  
Ji Yun Jung ◽  
Sang Mi Park ◽  
Hae Li Ko ◽  
Jong Rok Lee ◽  
Chung A Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Caspase 3 ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation ◽  
Anti Oxidant

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

scholarly journals Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis

2017 ◽  
Vol 8 ◽  
Author(s):  
Áislan de Carvalho Vivarini ◽  
Teresa Cristina Calegari-Silva ◽  
Alessandra Mattos Saliba ◽  
Viviane Sampaio Boaventura ◽  
Jaqueline França-Costa ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cutaneous Leishmaniasis ◽  
Systems Approach ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protein Kinase R ◽  
Human Cutaneous Leishmaniasis

scholarly journals Myeloid Deletion of Nuclear Factor Erythroid 2−Related Factor 2 Increases Atherosclerosis and Liver Injury

2012 ◽  
Vol 32 (12) ◽  
pp. 2839-2846 ◽  
Author(s):  
Alan R. Collins ◽  
Anisha A. Gupte ◽  
Ruirui Ji ◽  
Maricela R. Ramirez ◽  
Laurie J. Minze ◽  
...  
Keyword(s):  
Liver Injury ◽  
Related Factor ◽  
Nuclear Factor

scholarly journals Roles of Dietary Bioactive Peptides in Redox Balance and Metabolic Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Qinqin Qiao ◽  
Liang Chen ◽  
Xiang Li ◽  
Xiangyang Lu ◽  
Qingbiao Xu
Keyword(s):  
Protein Kinase ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Bioactive Peptides ◽  
Binding Protein ◽  
Biological Activities ◽  
Redox Balance ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Related Factor ◽  
Nuclear Factor

Bioactive peptides (BPs) are fragments of 2–15 amino acid residues with biological properties. Dietary BPs derived from milk, egg, fish, soybean, corn, rice, quinoa, wheat, oat, potato, common bean, spirulina, and mussel are reported to possess beneficial effects on redox balance and metabolic disorders (obesity, diabetes, hypertension, and inflammatory bowel diseases (IBD)). Peptide length, sequence, and composition significantly affected the bioactive properties of dietary BPs. Numerous studies have demonstrated that various dietary protein-derived BPs exhibited biological activities through the modulation of various molecular mechanisms and signaling pathways, including Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/antioxidant response element in oxidative stress; peroxisome proliferator-activated-γ, CCAAT/enhancer-binding protein-α, and sterol regulatory element binding protein 1 in obesity; insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B and AMP-activated protein kinase in diabetes; angiotensin-converting enzyme inhibition in hypertension; and mitogen-activated protein kinase and nuclear factor-kappa B in IBD. This review focuses on the action of molecular mechanisms of dietary BPs and provides novel insights in the maintenance of redox balance and metabolic diseases of human.

scholarly journals Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 346 ◽  
Author(s):  
Aladaileh ◽  
Abukhalil ◽  
Saghir ◽  
Hanieh ◽  
Alfwuaires ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Liver Injury ◽  
Oxidative Damage ◽  
Biological Activities ◽  
B Cell Lymphoma ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Acceptor

Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.

scholarly journals Protective Effects of Fucoxanthin against Alcoholic Liver Injury by Activation of Nrf2-Mediated Antioxidant Defense and Inhibition of TLR4-Mediated Inflammation

Marine Drugs ◽  
2019 ◽  
Vol 17 (10) ◽  
pp. 552 ◽  
Author(s):  
Jiawen Zheng ◽  
Xiaoxiao Tian ◽  
Wen Zhang ◽  
Pingan Zheng ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Liver Tissue ◽  
Inflammatory Responses ◽  
Serum Marker ◽  
Protective Mechanism ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Alcoholic Liver Injury

Fucoxanthin (Fx) is a natural extract from marine seaweed that has strong antioxidant activity and a variety of other bioactive effects. This study elucidated the protective mechanism of Fx on alcoholic liver injury. Administration of Fx was associated with lower pathological effects in liver tissue and lower serum marker concentrations for liver damage induced by alcohol. Fx also alleviated oxidative stress, and lowered the level of oxides and inflammation in liver tissue. Results indicate that Fx attenuated alcohol-induced oxidative lesions and inflammatory responses by activating the nuclear factor erythrocyte-2-related factor 2 (Nrf2)-mediated signaling pathway and down-regulating the expression of the toll-like receptor 4 (TLR4)-mediated nuclear factor-kappa B (NF-κB) signaling pathway, respectively. Our findings suggest that Fx can be developed as a potential nutraceutical for preventing alcohol-induced liver injury in the future.

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