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 Bamboo Stems (Phyllostachys nigra variety henosis) Containing Polyphenol Mixtures Activate Nrf2 and Attenuate Phenylhydrazine-Induced Oxidative Stress and Liver Injury

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 114 ◽  
Author(s):  
Ji Hye Yang ◽  
Moon-Hee Choi ◽  
Chang-Su Na ◽  
Sam Seok Cho ◽  
Jae Hoon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Iron Overload ◽  
Liver Damage ◽  
Hepg2 Cells ◽  
Hepatoprotective Effect ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nrf2 Target Gene ◽  
Phyllostachys Nigra

This study was designed to investigate the hepatoprotective effect of bamboo stems using in vitro and in vivo experimental liver damage models. Ethyl acetate fraction of 80% ethanol extract of Phyllostachys nigra stem (PN3) containing polyphenols had a higher NQO1-ARE reporter gene activity as monitored by the activity of the NF-E2-related factor (Nrf2) antioxidant pathway in cells in comparison to extracts from other species and under other conditions. The Nrf2 was translocated from the cytosol to the nucleus in response to PN3, followed by induction of the Nrf2 target gene expression, including HO-1, GCL, and NQO-1 in HepG2 cells. Phosphorylation of Nrf2 in HepG2 cells was enhanced in PN3, which was mediated by PKCδ, ERK, and p38 MAPK. Consequently, PN3 inhibited arachidonic acid (AA) + iron-induced reactive oxygen species generation and glutathione depletion, and, thus, highlighted their role in cytotoxicity. Treatment with major polyphenols of PN3, including catechin, chlorogenic acid, caffeic acid, and p-coumaric acid, also improved AA + iron-mediated oxidative stress and, thus, improved cell viability. Treatment with phenylhydrazine in mice, i.e., the iron overload liver injury model, increased plasma alanine aminotransferase and aspartate aminotransferase levels and changed histological features in mice—a response that was almost completely blocked by PN3 administration. Moreover, PN3 extract mitigated phenylhydrazine-induced oxidative stress and inflammatory responses. Conclusively, PN3 can exert a hepatoprotective effect against iron overload-induced acute liver damage due to its antioxidant properties.

scholarly journals Prodigiosin Promotes Nrf2 Activation to Inhibit Oxidative Stress Induced by Microcystin-LR in HepG2 Cells

Toxins ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 403 ◽  
Author(s):  
Jihua Chen ◽  
Yuji Li ◽  
Fuqiang Liu ◽  
De-Xing Hou ◽  
Jingjing Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Anticancer Properties ◽  
Nrf2 Activation ◽  
Nrf2 Protein ◽  
Related Phase

Microcystin-LR (MC-LR), a cyanotoxin produced by cyanobacteria, induces oxidative stress in various types of cells. Prodigiosin, a red linear tripyrrole pigment, has been recently reported to have antimicrobial, antioxidative, and anticancer properties. How prodigiosin reacts to reactive oxygen species (ROS) induced by MC-LR is still undetermined. This study aimed to examine the effect of prodigiosin against oxidative stress induced by MC-LR in HepG2 cells. Ros was generated after cells were treated with MC-LR and was significantly inhibited with treatment of prodigiosin. In prodigiosin-treated cells, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-related phase II enzyme heme oxygenase-1 (HO-1) were increased. Besides, prodigiosin contributed to enhance nuclear Nrf2 level and repressed ubiquitination. Furthermore, prodigiosin promoted Nrf2 protein level and inhibited ROS in Nrf2 knocked down HepG2 cells. Results indicated that prodigiosin reduced ROS induced by MC-LR by enhancing Nrf2 translocation into the nucleus in HepG2 cells. The finding presents new clues for the potential clinical applications of prodigiosin for inhibiting MC-LR-induced oxidative injury in the future.

scholarly journals NRF2 as a regulator of cell metabolism and inflammation in cancer

2020 ◽  
Vol 41 (4) ◽  
pp. 405-416 ◽  
Author(s):  
Feng He ◽  
Laura Antonucci ◽  
Michael Karin
Keyword(s):  
Oxidative Stress ◽  
Cancer Risk ◽  
Poor Prognosis ◽  
Cell Metabolism ◽  
Transcriptional Regulator ◽  
Negative Control ◽  
Metabolic Reprogramming ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation

Abstract Nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of genes whose products defend our cells for toxic and oxidative insults. Although NRF2 activation may reduce cancer risk by suppressing oxidative stress and tumor-promoting inflammation, many cancers exhibit elevated NRF2 activity either due to mutations that disrupt the negative control of NRF2 activity or other factors. Importantly, NRF2 activation is associated with poor prognosis and NRF2 has turned out to be a key activator of cancer-supportive anabolic metabolism. In this review, we summarize the diverse roles played by NRF2 in cancer focusing on metabolic reprogramming and tumor-promoting inflammation.

scholarly journals S-Allyl Cysteine Alleviates Hydrogen Peroxide Induced Oxidative Injury and Apoptosis through Upregulation of Akt/Nrf-2/HO-1 Signaling Pathway in HepG2 Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Chitra Basu ◽  
Runa Sur
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Cell Viability Assay

Hydrogen peroxide (H2O2) mediated oxidative stress leading to hepatocyte apoptosis plays a pivotal role in the pathophysiology of several chronic liver diseases. This study demonstrates that S-allyl cysteine (SAC) renders cytoprotective effects on H2O2 induced oxidative damage and apoptosis in HepG2 cells. Cell viability assay showed that SAC protected HepG2 cells from H2O2 induced cytotoxicity. Further, SAC treatment dose dependently inhibited H2O2 induced apoptosis via decreasing the Bax/Bcl-2 ratio, restoring mitochondrial membrane potential (∆Ψm), inhibiting mitochondrial cytochrome c release, and inhibiting proteolytic cleavage of caspase-3. SAC protected cells from H2O2 induced oxidative damage by inhibiting reactive oxygen species accumulation and lipid peroxidation. The mechanism underlying the antiapoptotic and antioxidative role of SAC is the induction of the heme oxygenase-1 (HO-1) gene in an NF-E2-related factor-2 (Nrf-2) and Akt dependent manner. Specifically SAC was found to induce the phosphorylation of Akt and enhance the nuclear localization of Nrf-2 in cells. Our results were further confirmed by specific HO-1 gene knockdown studies which clearly demonstrated that HO-1 induction indeed played a key role in SAC mediated inhibition of apoptosis and ROS production in HepG2 cells, thus suggesting a hepatoprotective role of SAC in combating oxidative stress mediated liver diseases.

scholarly journals Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators on Cardiac Fibrosis via NRF2 Activation

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1259
Author(s):  
Gyeoung Jin Kang ◽  
Eun Ji Kim ◽  
Chang Hoon Lee
Keyword(s):  
Oxidative Stress ◽  
Cardiac Fibrosis ◽  
Lipid Mediators ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Nuclear Factor ◽  
Docosahexanoic Acid ◽  
Nrf2 Activation ◽  
The World ◽  
Polyunsaturated Lipids

Heart disease is the number one mortality disease in the world. In particular, cardiac fibrosis is considered as a major factor causing myocardial infarction and heart failure. In particular, oxidative stress is a major cause of heart fibrosis. In order to control such oxidative stress, the importance of nuclear factor erythropoietin 2 related factor 2 (NRF2) has recently been highlighted. In this review, we will discuss the activation of NRF2 by docosahexanoic acid (DHA), eicosapentaenoic acid (EPA), and the specialized pro-resolving lipid mediators (SPMs) derived from polyunsaturated lipids, including DHA and EPA. Additionally, we will discuss their effects on cardiac fibrosis via NRF2 activation.

scholarly journals Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojun Pang ◽  
Emmanuel Ayobami Makinde ◽  
Fredrick Nwude Eze ◽  
Opeyemi Joshua Olatunji
Keyword(s):  
Oxidative Stress ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Diabetic Encephalopathy ◽  
Y Maze ◽  
Securidaca Inappendiculata

Diabetic encephalopathy is one of the serious emerging complication of diabetes. Securidaca inappendiculata is an important medicinal plant with excellent antioxidant and anti-inflammatory properties. This study investigated the neuroprotective effects of S. inappendiculata polyphenol rich extract (SiPE) against diabetic encephalopathy in rats and elucidated the potential mechanisms of action. Type 2 diabetes mellitus (T2DM) was induced using high fructose solution/intraperitoneal injection of streptozotocin and the diabetic rats were treated with SiPE (50, 100 and 200 mg/kg) for 8 weeks. Learning and memory functions were assessed using the Morris water and Y maze tests, depressive behaviour was evaluated using forced swimming and open field tests, while neuropathic pain assessment was assessed using hot plate, tail immersion and formalin tests. After the experiments, acetylcholinesterase (AChE), oxidative stress biomarkers and proinflammatory cytokines, caspase-3 and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) were determined by ELISA kits. In addition, the expression levels of p38, phospho-p38 (p-p38), nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by western blot analyses. The results indicated that SiPE administration significantly lowered blood glucose level, attenuated body weight loss, thermal/chemical hyperalgesia, improved behavioural deficit in the Morris water maze, Y maze test and reduced depressive-like behaviours. Furthermore, SiPE reduced AChE, caspase-3, NF-κB, malonaldehyde malondialdehyde levels and simultaneously increased antioxidant enzymes activity in the brain tissues of diabetic rats. SiPE administration also significantly suppressed p38 MAPK pathway and upregulated the Nrf2 pathway. The findings suggested that SiPE exerted antidiabetic encephalopathy effects via modulation of oxidative stress and inflammation.

scholarly journals Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Meiyu Jin ◽  
Haihua Feng ◽  
Yue Wang ◽  
Siru Yan ◽  
Bingyu Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Regulatory Element ◽  
Cell Counting ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Akt Inhibitor

The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is closely related to the alleviation of nonalcoholic fatty liver disease (NAFLD) by regulating oxidative stress and lipid homeostasis. Gentiopicroside (GPS), an iridoid glycoside found in the Gentianaceae, possesses anti-inflammatory and antioxidant effects. However, the protective effects of GPS on lipid accumulation and oxidative damage have not been investigated thoroughly in free fatty acid- (FFA-) induced HepG2 cells and tyloxapol- (Ty-) induced hyperlipidemia mice. Cell counting kit-8 assays, Oil Red O staining, Western blotting analysis, extraction of nuclear and cytosolic proteins, and biochemical index assay were employed to explore the mechanisms by which GPS exerts a protective effect on FFA-induced HepG2 cells and Ty-induced hyperlipidemia mouse model. This paper demonstrates that GPS could effectively alleviate NAFLD by elevating cell viability, reducing fatty deposition, downregulating TG, and activating nucleus Nrf2 in FFA-induced HepG2 cells. Meanwhile, GPS significantly regulated the activation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, Nrf2 antioxidant pathway, peroxisome proliferator-activated receptor α (PPARα), and GPS-inhibited sterol regulatory element-binding protein-1c (SREBP-1c) expression in FFA-stimulated lipid accumulation of HepG2 cells and Ty-treated mice. Interestingly, we highlight that PI3K/AKT inhibitor (LY294002) markedly increased the expression of Nrf2 antioxidant pathway, PPARα, and downregulated SREBP-1c in FFA-stimulated HepG2 cells. For these reasons, we found that the deletion of Nrf2 could lose the protective effects of GPS on the Nrf2 antioxidant pathway and PPARα activation and SREBP-1c inactivation in FFA-stimulated HepG2 cells and Ty-treated mice. GPS treatment had no effect on abnormal lipogenesis and antioxidant enzymes in Ty-induced Nrf2-/- mice. This work gives a new explanation that GPS may be a useful therapeutic strategy for NAFLD through upregulation of the Nrf2 antioxidant pathway, which can alleviate oxidative damage and lipid accumulation.

scholarly journals Lutein Has a Protective Effect on Hepatotoxicity Induced by Arsenic via Nrf2 Signaling

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shugang Li ◽  
Yusong Ding ◽  
Qiang Niu ◽  
Shangzhi Xu ◽  
Lijuan Pang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Arsenic Trioxide ◽  
Liver Diseases ◽  
Critical Role ◽  
Hepatic Function ◽  
Related Factor ◽  
Nuclear Factor ◽  
Mice Model ◽  
Mrna And Protein Expression ◽  
Oxidative Species

Arsenic produces liver disease through the oxidative stress. While lutein can alleviate cytotoxic and oxidative injury, nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a critical role in defending oxidative species. However, the mechanisms by which lutein protects the liver against the effect of arsenic are not known. Therefore, this study aims to investigate the mechanisms involved in the action of lutein using mice model in which hepatotoxicity was induced by arsenic. We found that mice treatment with lutein could reverse changes in morphological and liver indexes and result in a significant improvement in hepatic function comparing with arsenic trioxide group. Lutein treatment improved the activities of antioxidant enzymes and attenuated increasing of ROS and MDA induced by arsenic trioxide. Lutein could increase the mRNA and protein expression of Nrf2 signaling related genes (Nrf2, Nqo1, Ho-1, and Gst). These findings provide additional evidence that lutein may be useful for reducing reproductive injury associated with oxidative stress by the activation of Nrf2 signaling. Our findings suggest a possible mechanism of antioxidant lutein in preventing the hepatotoxicity, which implicate that a dietary lutein may be a potential treatment for liver diseases, especially for arsenicosis therapy.

scholarly journals Polydatin Protects Rat Liver against Ethanol-Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF-κB p65 Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Qiong-Hui Huang ◽  
Lie-Qiang Xu ◽  
Yu-Hong Liu ◽  
Jia-Zhen Wu ◽  
Xue Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Target Gene ◽  
Related Factor ◽  
Nuclear Factor ◽  
Toll Like Receptor 4 ◽  
Excessive Alcohol Consumption ◽  
Excessive Alcohol ◽  
Haem Oxygenase ◽  
Effect Of Pd

Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD) exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the serum, suppressed the malonaldehyde (MDA) and triglyceride (TG) content and the production of reactive oxygen species (ROS), and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), andalcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target gene haem oxygenase-1 (HO-1). Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) via downregulating toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

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