scholarly journals Mogroside V Alleviates Lipopolysaccharide-Induced Neuroinflammation via Inhibition of TLR4-MyD88 and Activation of AKT/AMPK-Nrf2 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yuanyuan Liu ◽  
Boxi Zhang ◽  
Jiahe Liu ◽  
Chunyu Qiao ◽  
Nianyu Xue ◽  
...  
Keyword(s):  
Nervous System ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Neuronal Damage ◽  
Neurological Diseases ◽  
High Mobility ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Signaling Pathway

As innate immune effector cells in the central nervous system (CNS), microglia not only are essential for the normal development of nervous system but also act on different neurological diseases, including Alzheimer’s disease (AD), Huntington's disease (HD), and other neuroinflammatory diseases. Mogroside V (Mog), a natural plant active ingredient and isolated form of Momordica grosvenori, has been shown to possess anti-inflammatory action, but few studies were carried out to investigate the effects of Mog on neuroinflammation. This study aimed to investigate the role of Mog in lipopolysaccharide- (LPS-) induced neuroinflammation and neuronal damage, revealing the underlying mechanisms. Our data indicated that Mog significantly inhibited the LPS-induced production of proinflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-18, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and high mobility group box 1 (HMGB1) in BV-2 cells. We found that Mog also suppressed toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), the phosphorylation of mitogen-activated protein kinases (MAPKs), adenosine 5′-monophosphate- (AMP-) activated protein kinase (AMPK), nuclear factor kappa-B (NF-κB), and protein kinase B (AKT). Moreover, Mog also enhanced the expression of γ-glutamyl cysteine synthetase catalytic subunit (GCLC), modifier subunit (GCLM), heme oxygenase-1 (HO-1), and quinine oxidoreductase 1 (NQO1) proteins, mostly depending on the nuclear translation of nuclear factor erythroid-2 related factor 2 (Nrf2). In contrast, pretreatment with inhibitors of AKT can suppress the phosphorylation of AMPK, Nrf2, and its downstream proteins expression. In summary, Mog might play a protective role against LPS-induced neurotoxicity by inhibiting the TLR4-MyD88 and activation of AMPK/AKT-Nrf2 signaling pathway.

scholarly journals Clusterin Protects Against Cr(VI)-Induced Oxidative Stress-Associated Hepatotoxicity By Mediating The Akt-Keap1-Nrf2 Signaling Pathway

2021 ◽  
Author(s):  
Yu Ma ◽  
Siwen Li ◽  
Sixuan Tang ◽  
Shuzi Ye ◽  
Ningjuan Liang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Environmental Pollutant ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Intervention Measures ◽  
Exposed Population ◽  
Nrf2 Signaling Pathway

Abstract Hexavalent chromium [Cr(VI)] is a serious environmental pollutant and threatens human health. Although it has been confirmed that oxidative stress is the main mechanism of liver injury caused by Cr(VI) exposure, the related toxic target and effective intervention measures have not been found. Clusterin (CLU) is an acute phase response protein with cytoprotective and apoptosis delaying effects, and its expression has been confirmed to increase significantly after exposure to Cr(VI). In this study, we demonstrate that CLU acts on the Protein Kinase B (PKB/Akt)-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway to release Nrf2 into the nucleus. This to initiates the expression of a downstream protein, heme oxygenase 1 (HO-1), thereby attenuating the ubiquitination ability of Keap1 with Nrf2. We also demonstrated that CLU can affect oxidative stress through the Akt/Nrf2 pathway, which reduces the production of reactive oxygen species (ROS) induced by Cr(VI) and protects against Cr(VI)-induced oxidative stress-associated hepatotoxicity. This study demonstrates a the mechanism of Cr(VI)-induced hepatotoxicity, and indicates that CLU as an intervention target of oxidative stress can provide valuable experimental basis for the prevention and treatment of occupational diseases in Cr(VI)-exposed population.

scholarly journals Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2-Keap1 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Guosheng Lin ◽  
Dandan Luo ◽  
Jingjing Liu ◽  
Xiaoli Wu ◽  
Jinfen Chen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Hepatoprotective Effect ◽  
Dendrobium Officinale ◽  
Regulatory Subunit ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Glutamate Cysteine Ligase ◽  
Nrf2 Signaling Pathway

The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real-time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2−Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP-mediated Nrf2 activation triggered the transcription and expressions of the glutamate–cysteine ligase catalytic (GCLC) subunit, glutamate–cysteine ligase regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP-induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2−Keap1 signaling pathway.

scholarly journals Bovine Herpesvirus 1 Productive Infection Led to Inactivation of Nrf2 Signaling through Diverse Approaches

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Xiaotian Fu ◽  
Dongmei Chen ◽  
Yan Ma ◽  
Weifeng Yuan ◽  
Liqian Zhu
Keyword(s):  
Signaling Pathway ◽  
Bovine Herpesvirus ◽  
Productive Infection ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Quinone Oxidoreductase ◽  
Herpesvirus Type ◽  
Nrf2 Signaling Pathway ◽  
Mdbk Cells ◽  
Bovine Herpesvirus Type 1

Bovine herpesvirus type 1 (BoHV-1) is a significant cofactor for bovine respiratory disease complex (BRDC), the most important inflammatory disease in cattle. BoHV-1 infection in cell cultures induces overproduction of pathogenic reactive oxygen species (ROS) and the depletion of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a master transcriptional factor regulating a panel of antioxidant and cellular defense genes in response to oxidative stress. In this study, we reported that the virus productive infection in MDBK cells at the later stage significantly decreased the expression levels of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO1) proteins, the canonical downstream targets regulated by Nrf2, inhibited Nrf2 acetylation, reduced the accumulation of Nrf2 proteins in the nucleus, and relocalized nuclear Nrf2 proteins to form dot-like staining patterns in confocal microscope assay. The differential expression of Kelch-like ECH associated protein 1 (KEAP1) and DJ-1 proteins as well as the decreased association between KEAP1 and DJ-1 promoted Nrf2 degradation through the ubiquitin proteasome pathway. These data indicated that the BoHV-1 infection may significantly suppress the Nrf2 signaling pathway. Moreover, we found that there was an association between Nrf2 and LaminA/C, H3K9ac, and H3K18ac, and the binding ratios were altered following the virus infection. Taken together, for the first time, we provided evidence showing that BoHV-1 infection inhibited the Nrf2 signaling pathway by complicated mechanisms including promoting Nrf2 degradation, relocalization of nuclear Nrf2, and inhibition of Nrf2 acetylation.

l-carnitine protects human hepatocytes from oxidative stress-induced toxicity through Akt-mediated activation of Nrf2 signaling pathway

2016 ◽  
Vol 94 (5) ◽  
pp. 517-525 ◽  
Author(s):  
Jinlian Li ◽  
Yanli Zhang ◽  
Haiyun Luan ◽  
Xuehong Chen ◽  
Yantao Han ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Cell Damage ◽  
Binding Activity ◽  
Akt Pathway ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Akt Inhibitor ◽  
Nrf2 Signaling Pathway

In our previous study, l-carnitine was shown to have cytoprotective effect against hydrogen peroxide (H2O2)-induced injury in human normal HL7702 hepatocytes. The aim of this study was to investigate whether the protective effect of l-carnitine was associated with the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) pathway. Our results showed that pretreatment with l-carnitine augmented Nrf2 nuclear translocation, DNA binding activity and heme oxygenase-1 (HO-1) expression in H2O2-treated HL7702 cells, although l-carnitine treatment alone had no effect on them. Analysis using Nrf2 siRNA demonstrated that Nrf2 activation was involved in l-carnitine-induced HO-1 expression. In addition, l-carnitine-mediated protection against H2O2 toxicity was abrogated by Nrf2 siRNA, indicating the important role of Nrf2 in l-carnitine-induced cytoprotection. Further experiments revealed that l-carnitine pretreatment enhanced the phosphorylation of Akt in H2O2-treated cells. Blocking Akt pathway with inhibitor partly abrogated the protective effect of l-carnitine. Moreover, our finding demonstrated that the induction of Nrf2 translocation and HO-1 expression by l-carnitine directly correlated with the Akt pathway because Akt inhibitor showed inhibitory effects on the Nrf2 translocation and HO-1 expression. Altogether, these results demonstrate that l-carnitine protects HL7702 cells against H2O2-induced cell damage through Akt-mediated activation of Nrf2 signaling pathway.

scholarly journals Cytoprotective Effect of Ligustrum robustum Polyphenol Extract against Hydrogen Peroxide-Induced Oxidative Stress via Nrf2 Signaling Pathway in Caco-2 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Jiayi Chen ◽  
Fangting He ◽  
Sijing Liu ◽  
Tao Zhou ◽  
Saira Baloch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Signaling Pathway ◽  
Total Phenolic ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cytoprotective Effect ◽  
Quinone Oxidoreductase ◽  
Antioxidant Genes ◽  
Nrf2 Signaling Pathway

Ligustrum robustum is a traditional herbal tea that is widely distributed in southwest China. The health effects of L. robustum are characteristics of clearing heat, antioxidant, inducing resurgence, and improving digestion. However, the molecular mechanisms related to these effects, particularly the antioxidant mechanism, have been seldom reported. The objective of this study was to assess antioxidative capacity of L. robustum, and its protective effects and mechanisms against hydrogen peroxide (H2O2) - induced toxicity in Caco-2 cells. Total phenolic contents, free radical scavenging activity, and reducing capacity of L. robustum were measured. The effects of L. robustum on the cell viability and antioxidant defense system were explored. The expression of nuclear factor E2 related factor 2 (Nrf2) and antioxidant genes: quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutamate cysteine ligase (GCL) were analyzed by western blot and qPCR. Pretreatment of L. robustum could significantly reduce H2O2-induced toxicity, decrease the level of reactive oxygen species (ROS) and malondialdehyde (MDA), and increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR). By activating the expression of Nrf2 and antioxidant genes (NQO1, HO-1, and GCL), L. robustum exerts cytoprotective effect in Caco-2 cells dealt with H2O2. Therefore, the well-established model of Caco-2 cells demonstrates that L. robustum may modulate the cytoprotective effect against the H2O2-induced oxidative stress through the Nrf2 signaling pathway.

The Effects of Naringin on Cigarette Smoke-Induced Dynamic Changes in Oxidation/Antioxidant System in Lung of Mice

2020 ◽  
Vol 15 (8) ◽  
pp. 1934578X2094723
Author(s):  
Pan Chen ◽  
Ziting Xiao ◽  
Hao Wu ◽  
Yonggang Wang ◽  
Weiwei Su ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Cigarette Smoke ◽  
Antioxidant System ◽  
Antioxidant Systems ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dynamic Changes ◽  
Tnf Α ◽  
Nrf2 Signaling Pathway

Naringin possesses strong antioxidative activity and can protect against some respiratory diseases. Oxidative stress is thought to be a major factor in the development of many tobacco-caused diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a critical role in the regulation of oxidative stress. The dynamic changes in the antioxidant system in the lung that are induced by cigarette smoke (CS) are not well investigated, and how naringin affects these changes remains unknown. This study aimed to investigate the dynamic changes between the oxidation and antioxidant systems resulting from CS exposure and the effects of naringin on these changes in mice. Mice were chronically exposed to CS for 30 days. The levels of malondialdehyde (MDA), glutathione (GSH), interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-α); the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px); and the expressions of Nrf2, heme oxygenase-1 (HO-1), and nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1) in lung tissue were measured on days 2, 7, and 30. The levels of MDA, GSH, IL-6, and TNF-α in the lung were found to increase throughout the exposure. SOD and GSH-Px activities showed an increase on day 2 and a decrease on days 7 and 30. The messenger ribonucleic acid expressions of Nrf2, HO-1, and NQO1 were elevated on day 2 and decreased on day 7; Nrf2 and HO-1 expressions were continually decreased, but NQO1 expression was increased again, on day 30. Naringin restored the levels of these biochemical indices to normal throughout the experiment, suggesting that naringin protected against the CS-induced oxidative damage by suppressing the increase of antioxidants resulting from the early stage of CS exposure, as well as inhibiting the depletion of antioxidants due to long-term oxidative stress. Naringin also suppressed lung inflammation by inhibiting IL-6 and TNF-α. These results indicate that naringin possesses a powerful ability to maintain the balance of the oxidation/antioxidant system in the lung when subjected to CS exposure, probably by regulating the Nrf2 signaling pathway.

scholarly journals Mn-TAT PTD-Ngb attenuates oxidative injury by an enhanced ROS scavenging ability and the regulation of redox signaling pathway

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cui Zhang ◽  
Xuehui Hao ◽  
Jiaying Chang ◽  
Zhirong Geng ◽  
Zhilin Wang
Keyword(s):  
Signaling Pathway ◽  
Redox Regulation ◽  
Protective Factor ◽  
Neurological Diseases ◽  
Oxidative Injury ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Manganese Porphyrin ◽  
Ros Scavenging ◽  
Close Relationship

AbstractNeurological diseases have a close relationship to excessive reactive oxygen species (ROS). Neuroglobin (Ngb), an intrinsic protective factor, protected cells from hypoxic/ischemic injury. In the present, we reported a novel neuroprotective manganese porphyrin reconstituted metal protein, Mn-TAT PTD-Ngb, consisting of a HIV Tat protein transduction domain sequence (TAT PTD) attached to the N-terminal of apo-Ngb. Mn-TAT PTD-Ngb had a stronger ROS scavenging ability than that of TAT PTD-Ngb, and reduced intracellular ROS production and restored the function of the mitochondria and inhibited the mitochondria-dependent apoptosis. Besides, Mn-TAT PTD-Ngb activated the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway, which up-regulated the expression of nuclear factor E2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT). The results showed that the redox chemistry of Mn-TAT PTD-Ngb and redox regulation of multiple signaling pathways attenuated the oxidative injury.

scholarly journals Effects of Launaea sarmentosa Extract on Lipopolysaccharide-Induced Inflammation via Suppression of NF-κB/MAPK Signaling and Nrf2 Activation

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2586 ◽  
Author(s):  
Thanh Q. C. Nguyen ◽  
Tran Duy Binh ◽  
Ryo Kusunoki ◽  
Tuan L. A. Pham ◽  
Yen D. H. Nguyen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Akt Phosphorylation

Launaea sarmentosa has been extensively used as a nutrient herb in traditional Vietnamese remedies for the treatment of various diseases, especially inflammatory diseases. However, no detailed research has been conducted examining the molecular mechanisms involved in the suppression of inflammatory response. Here, we studied the effects of L. sarmentosa methanol extract on lipopolysaccharide (LPS)-induced inflammation using RAW 264.7 macrophages. The extract demonstrated potent antioxidant activity owing to the presence of polyphenolic and flavonoid components. Pretreatment with the extract inhibited LPS-mediated secretion of nitric oxide, reactive oxygen species, and tumor necrosis factor-α as well as the expression of inflammatory cytokines. Furthermore, the activation of the nuclear factor-kappa B pathway and phosphoinositide-3-kinase/protein kinase B pathways was blocked by the extract by inhibiting Akt phosphorylation. Additionally, the mitogen-activated protein kinase pathway was suppressed, and endoplasmic reticulum stress was attenuated. Furthermore, the extract promoted the activity of nuclear factor erythroid-2-related factor 2 resulting in the up-regulation of heme oxygenase-1 pathway, leading to the suppression of oxidative stress and inflammatory response. Taken together, the results indicate that L. sarmentosa exhibits anti-inflammatory effects, and hence, can be further developed as a novel drug for the treatment of diseases associated with excessive inflammation.

1-Bromopropane-induced apoptosis in OVCAR-3 cells via oxidative stress and inactivation of Nrf2

2020 ◽  
pp. 074823372097942
Author(s):  
Guangtao Yang ◽  
Yingping Xiang ◽  
Wei Zhou ◽  
Xiaohuan Zhong ◽  
Yanfang Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Reproductive Toxicity ◽  
Antioxidant Vitamin ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ovarian Carcinoma Cell Line ◽  
Nrf2 Signaling Pathway ◽  
Induced Apoptosis

The bromoalkane, 1-bromopropane (1-BP), may damage the reproductive system though oxidative stress, while the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in regulating intracellular antioxidant levels against oxidative stress. This study explored the role of oxidative stress and the Nrf2 signaling pathway in mediating the reproductive toxicity of 1-BP using the ovarian carcinoma cell line OVCAR-3 as an in vitro model of the human ovary. OVCAR-3 cells were treated with 1, 5, 10 and 15 mM 1-BP. After 24 h, the cellular reactive oxygen species and malondialdehyde concentrations significantly increased, while the superoxide dismutase activity decreased; translocation of Nrf2 from the cytosol to the nucleus as well as downstream protein expression of Nrf2-regulated genes heme oxygenase-1 and Bcl-2 was inhibited. Apoptosis was also observed, accompanied by increased caspase-3 and caspase-9 activity. The antioxidant vitamin C alleviated 1-BP-induced apoptosis by inhibiting caspase activity activating the Nrf2 signaling pathway. These findings suggested that 1-BP induced oxidative stress and apoptosis in OVCAR-3 cells through inactivation of Nrf2 signaling.

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