AGE-Rich Bread Crust Extract Boosts Oxidative Stress Interception via Stimulation of the NRF2 Pathway

Advanced glycation end products (AGEs) result from a non-enzymatic reaction of proteins with reactive carbohydrates. Heat-processed food, such as bread, contains high amounts of AGEs. The activation of the NF-κB signaling pathway by bread crust extract (BCE) is well understood. However, it is largely unknown whether NRF2, the master regulator of oxidative stress resistance in mammalian cells, is affected by BCE. We have investigated the molecular mechanisms by which BCE induces antioxidant gene expression in cellular models. Our data showed that soluble extracts from bread crust are capable of stimulating the NRF2 signaling pathway. Furthermore, NRF2 pathway activation was confirmed by microarray and reporter-cell analyses. QRT-PCR measurements and Western blot analyses indicated an induction of antioxidative genes such as HMOX1, GCLM and NQO1 upon BCE treatment. Moreover, BCE pretreated cells had a survival advantage compared to control cells when exposed to oxidative stress. BCE induces phosphorylation of AKT and ERK kinase in EA.hy926 cells. By mass spectrometry, several new, potentially active modifications in BCE were identified. Our findings indicate that BCE activates NRF2-dependent antioxidant gene expression, thus provoking a protection mechanism against oxidative stress-mediated tissue injury. Hence, BCE can be considered as functional food with antioxidative and cardioprotective potential.

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Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury through PI3K/Akt-Mediated Nrf2 Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7591840 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 14

Author(s):

Yu Zhuang ◽

Huirong Wu ◽

Xiangxiang Wang ◽

Jieyu He ◽

Shanping He ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Signaling Pathway ◽

Intestinal Damage ◽

Dependent Manner ◽

Antioxidant Gene ◽

Expression Levels ◽

Protein Levels ◽

Nrf2 Signaling Pathway ◽

Antioxidant Gene Expression

Oxidative stress is implicated in a wide range of intestinal disorders and closely associated with their pathological processes. Resveratrol (RSV), a plant extract, plays a vital role in protecting various organs in vitro and in vivo. However, the benefits of RSV are controversial, and underlying mechanisms for its antioxidant effects on intestinal epithelial cells remain unclear. In this study, we evaluated the effects of RSV on oxidative stress induced by H2O2 in IPEC-J2 cells. We found that pretreatment with RSV significantly increased cell viability; increased expression levels of tight junction (TJ) proteins (claudin-1, occludin, and ZO-1); improved activities of superoxide dismutase-1 (SOD-1), catalase (CAT), and glutathione peroxidase (GSH-Px); and decreased intracellular reactive oxygen species (ROS) levels and apoptosis induced by H2O2 (P<0.05). In addition, RSV upregulated Akt phosphorylation, Nrf2 phosphorylation, and expression levels of antioxidant genes HO-1, SOD-1, and CAT in a dose-dependent manner (P<0.05) under oxidative stress. Knockdown of Nrf2 by short-hairpin RNA (shRNA) abrogated RSV-mediated protection against H2O2-induced apoptosis, RSV-induced increase of TJ protein levels, and antioxidant gene expression (SOD-1, CAT, and GSH-Px) (P<0.05). Consistent with Nrf2 knockdown, the PI3K/Akt inhibitor LY294002 significantly suppressed RSV-induced Nrf2 phosphorylation and RSV-induced increase of TJ protein levels and antioxidant gene expression under H2O2 treatment (P<0.05). Collectively, these results demonstrate that RSV can directly protect IPEC-J2 cells against oxidative stress through the PI3K/Akt-mediated Nrf2 signaling pathway, suggesting that RSV may be an effective feed additive against intestinal damage in livestock production.

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Effects of zearalenone-induced oxidative stress and Keap1–Nrf2 signaling pathway-related gene expression in the ileum and mesenteric lymph nodes of post-weaning gilts

Toxicology ◽

10.1016/j.tox.2019.152337 ◽

2020 ◽

Vol 429 ◽

pp. 152337 ◽

Cited By ~ 4

Author(s):

Qun Cheng ◽

Shuzhen Jiang ◽

Libo Huang ◽

Yuxi Wang ◽

Weiren Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Lymph Nodes ◽

Signaling Pathway ◽

Related Gene ◽

Mesenteric Lymph Nodes ◽

Mesenteric Lymph ◽

Nrf2 Signaling Pathway

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Dietary resveratrol improves antioxidant status of sows and piglets and regulates antioxidant gene expression in placenta by Keap1-Nrf2 pathway and Sirt1

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-018-0248-y ◽

2018 ◽

Vol 9 (1) ◽

Cited By ~ 25

Author(s):

Qingwei Meng ◽

Tao Guo ◽

Gaoqiang Li ◽

Shishuai Sun ◽

Shiqi He ◽

...

Keyword(s):

Gene Expression ◽

Antioxidant Status ◽

Antioxidant Gene ◽

Nrf2 Pathway ◽

Antioxidant Gene Expression

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The Role of Nrf2 Signaling Pathway in Eucommia ulmoides Flavones Regulating Oxidative Stress in the Intestine of Piglets

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/9719618 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Dingfu Xiao ◽

Daixiu Yuan ◽

Bihui Tan ◽

Jing Wang ◽

Yanhong Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Mrna Expression ◽

Signaling Pathway ◽

Basal Diet ◽

Heme Oxygenase 1 ◽

Intestinal Damage ◽

Eucommia Ulmoides ◽

Nrf2 Pathway ◽

Nrf2 Signaling Pathway ◽

Protein Expressions

Eucommia ulmoides flavones (EUF) have been demonstrated to alleviate oxidative stress and intestinal damage in piglets, but their effect target is still poorly understood. NF-E2-related factor 2 (Nrf2) pathway plays a very important role in the defense mechanism. This study was designed to investigate the regulation of EUF on the Nrf2 pathway and inhibition of Nrf2 on oxidative stress in the intestine of piglets. An in vivo study was conducted in weaned piglets treated with basal diet, basal diet+diquat, and 100 mg/kg EUF diet+diquat for 14 d to determine Nrf2 and Keap1 protein expressions, as well as downstream antioxidant gene mRNA expression. An in vitro study was performed in a porcine jejunal epithelial cell line to investigate the effect of inhibiting Nrf2 on cell growth and intracellular oxidative stress parameters. The results showed that the supplementation of EUF decreased the oxidized glutathione (GSSG) concentration and the ratio of GSSG to glutathione (GSH) but increased the protein expressions of nuclear Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) as well as mRNA expression of heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1), and glutamate cysteine ligase catalytic subunit (GCLC) in the small intestinal mucosa of diquat-challenged piglets. When Nrf2 was inhibited by using ML385, cell viability, cellular antioxidant activities, expressions of nuclear Nrf2 and Keap1 protein, and downstream antioxidant enzyme (HO-1, NQO-1, and GCLC) mRNA were decreased in paraquat-treated enterocytes. These results showed that the Nrf2 signaling pathway played an important role in EUF-regulating oxidative stress in the intestine of piglets.

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In response to oxidative stress, the expression of inflammatory cytokines and antioxidant enzymes are impaired in placenta, but not adipose tissue, of women with gestational diabetes

Journal of Endocrinology ◽

10.1677/joe-09-0321 ◽

2009 ◽

Vol 204 (1) ◽

pp. 75-84 ◽

Cited By ~ 45

Author(s):

Martha Lappas ◽

Amberlee Mittion ◽

Michael Permezel

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Adipose Tissue ◽

Gestational Diabetes ◽

Pregnant Women ◽

Mrna Expression ◽

Human Placenta ◽

Cytokine Release ◽

Antioxidant Gene ◽

Antioxidant Gene Expression

In response to oxidative stress, gestational diabetes mellitus (GDM) placenta releases less 8-isoprostane and tumour necrosis factor (TNF) α. The effect of oxidative stress on other cytokines and antioxidant gene expressions are unknown. The aim of this study is to further explore the antioxidant status and effect of oxidative stress in GDM tissue. Human placenta, omental and subcutaneous adipose tissue from women with and without GDM were exposed to hypoxanthine (HX)/xanthine oxidase (XO). Cytokine release was analysed by ELISA and cytokine and antioxidant gene expression by RT-PCR. Catalase (CAT) and glutathione reductase (GSR) mRNA expression was higher in GDM (n=18) compared with normal (n=23) placenta. There was no difference in glutathione peroxidase and superoxide dismutase mRNA expression. Antioxidant gene expression was unaltered between normal (n=18) and GDM (n=10) adipose tissue. HX/XO treatment significantly stimulated cytokine release (13/16 cytokines) and cytokine mRNA expression, and decreased antioxidant gene expression (CAT and GSR) in human placenta from normal pregnant women. In GDM placenta, HX/XO only significantly increased the release of 3/16 cytokines, while there was no effect on antioxidant gene expression. In normal and GDM adipose tissues, HX/XO increased proinflammatory cytokine and 8-isoprostane release, while there was no change in antioxidant gene expression. GDM placenta is characterised by increased antioxidant gene expression, and is less responsive to exogenous oxidative stress than tissues obtained from normal pregnant women. This may represent a protective or adaptive mechanism to prevent damage from further oxidative insult in utero as indicated by increased tissue antioxidant expression.

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Dandelion Extract Alleviated Lipopolysaccharide-Induced Oxidative Stress through the Nrf2 Pathway in Bovine Mammary Epithelial Cells

Toxins ◽

10.3390/toxins12080496 ◽

2020 ◽

Vol 12 (8) ◽

pp. 496 ◽

Cited By ~ 1

Author(s):

Yawang Sun ◽

Yongjiang Wu ◽

Zili Wang ◽

Juncai Chen ◽

You Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Signaling Pathway ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Epithelial Cell Line ◽

Related Factor ◽

Nrf2 Pathway ◽

Bovine Mammary Epithelial Cells ◽

Nrf2 Signaling Pathway

In practical dairy production, cows are frequently subjected to inflammatory diseases, such as high-grain diet-induced subacute ruminal acidosis (SARA) as well as mastitis and metritis. Under the circumstances, lipopolysaccharide (LPS) induces oxidative stress within the cow and in the mammary epithelial cells. It has implications in practical production to alleviate oxidative stress and to optimize the lactational function of the mammary epithelial cells. This study thus aimed to investigate the antioxidative effects of dandelion aqueous extract (DAE) on LPS-induced oxidative stress and the mechanism of DAE as an antioxidant to alleviate oxidative stress through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the bovine mammary epithelial cell line MAC-T cells. The cells were cultured for 48 h in six treatments including control (without LPS and DAE), LPS (100 ng/mL), DAE10 (100 ng/mL LPS and 10 μg/mL DAE), DAE50 (100 ng/mL LPS and 50 μg/mL DAE), DAE100 (100 ng/mL LPS and 100 μg/mL DAE), and DAE200 (100 ng/mL LPS and 200 μg/mL DAE), respectively. The results showed that cell viability was reduced by LPS, and the adverse effect of LPS was suppressed with the supplementation of DAE. Lipopolysaccharide-induced oxidative stress through enhancing reactive oxygen species (ROS) production, resulted in increases in oxidative damage marker concentrations, while 10 and 50 μg/mL DAE alleviated the LPS-induced oxidative stress via scavenging cellular ROS and improving antioxidant enzyme activity. The upregulation of antioxidative gene expression in DAE treatments was promoted through activating the Nrf2 signaling pathway, with DAE at a concentration of 50 μg/mL exhibiting the highest effect. Overall, DAE acted as an effective antioxidant to inhibit LPS-induced oxidative stress and as a potential inducer of the Nrf2 signaling pathway.

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Alginate Oligosaccharide Ameliorates D-Galactose-Induced Kidney Aging in Mice through Activation of the Nrf2 Signaling Pathway

BioMed Research International ◽

10.1155/2021/6623328 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Hui Pan ◽

Wenjing Feng ◽

Ming Chen ◽

Hong Luan ◽

Yi Hu ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Aging Process ◽

Molecular Mechanisms ◽

Nuclear Translocation ◽

Heme Oxygenase 1 ◽

Quinone Oxidoreductase ◽

Nrf2 Signaling Pathway ◽

Wide Range ◽

Alginate Oligosaccharide

Aging is an independent risk factor for the development of age-related progressive kidney injury. As a part of the aging process, kidney aging has been indicated to be associated with oxidative stress-induced damage. Ameliorating oxidative damage is therefore considered a promising strategy for delaying kidney aging. Alginate oligosaccharide (AOS) has been reported to have a wide range of biological and pharmacological activities. However, no studies have focused on the role of AOS in delaying the kidney aging process. In this study, we aimed to evaluate the potential effects of AOS on kidney aging and its possible mechanisms. Subcutaneous injection of D-galactose (D-gal) (200 mg·kg-1·d-1) in C57BL/6J mice for 8 weeks was used to establish the aging model. AOS (200 mg·kg-1·d-1) was administered via oral gavage for the last four weeks. As a result, AOS inhibited the D-gal-induced upregulation of aging markers and significantly improved the kidney index and kidney function of D-gal-induced mice. In addition, AOS ameliorated the degree of tissue damage and fibrosis in the aging kidney. To further explore the potential mechanisms by which AOS attenuates the kidney aging process, the associated oxidative stress-induced damage was analyzed in depth. The data showed that AOS upregulated the expression of Klotho and decreased malondialdehyde levels by increasing the expression of antioxidant enzymes. Furthermore, our results suggested that AOS activated the nuclear factor erythrogen-2 associated factor 2 (Nrf2) pathway by promoting Nrf2 nuclear translocation in aging mice and upregulated the downstream expression of heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). In conclusion, the present study demonstrated that AOS is a promising agent for attenuating kidney aging, and the underlying molecular mechanisms are related to the activation of the Nrf2 signaling pathway.

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