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Nrf2 AND sulforaphane

Shu-Hua Yang, Miao Long, Li-Hui Yu, Lin Li, Peng Li, Yi Zhang, Yang Guo, Feng Gao, Ming-Da Liu, Jian-Bin He
Sulforaphane (SFN) is a natural and highly effective antioxidant. Studies suggest that SFN protects cells and tissues against cadmium (Cd) toxicity. This study investigated the protective effect of SFN against oxidative damage in the testes of Kunming mice exposed to cadmium, and explored the possible molecular mechanisms involved. Cadmium greatly reduced the serum testosterone levels in mice, reduced sperm motility, total sperm count, and increased the sperm deformity rate. Cadmium also reduces superoxide dismutase (T-SOD) and glutathione (GSH) levels and increases malondialdehyde (MDA) concentrations...
October 11, 2016: International Journal of Molecular Sciences
Dushani L Palliyaguru, Dionysios V Chartoumpekis, Nobunao Wakabayashi, John J Skoko, Yoko Yagishita, Shivendra V Singh, Thomas W Kensler
Small molecules of plant origin offer presumptively safe opportunities to prevent carcinogenesis, mutagenesis and other forms of toxicity in humans. However, the mechanisms of action of such plant-based agents remain largely unknown. In recent years the stress responsive transcription factor Nrf2 has been validated as a target for disease chemoprevention. Withania somnifera (WS) is a herb used in Ayurveda (an ancient form of medicine in South Asia). In the recent past, withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated to be preventive and therapeutic against multiple diseases in experimental models...
October 4, 2016: Free Radical Biology & Medicine
I S Haslam, L Jadkauskaite, Imre Lőrinc Szabó, S Staege, J Hesebeck-Brinckmann, G Jenkins, R Bhogal, F L Lim, N Farjo, B Farjo, T Bíró, M Schäfer, R Paus
The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of Nrf2, the "master regulator" of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ, human scalp hair follicles (HFs)...
October 1, 2016: Journal of Investigative Dermatology
Xudong Zhao, Liting Wen, Min Dong, Xiaojie Lu
Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behaviour in a rat model of SAH...
September 27, 2016: Brain Research
Junhui Shao, Jiang Huang, Yana Guo, Lijuan Li, Xueqin Liu, Xiaoxuan Chen, Junfa Yuan
Generation of reactive oxygen species (ROS) and failure to maintain an appropriate redox balance contribute to viral pathogenesis. Nuclear factor E2-related factor 2 (Nrf2) is an important transcription factor that plays a pivotal role in maintaining intracellular homoeostasis and coping with invasive pathogens by coordinately activating a series of cytoprotective genes. Previous studies indicated that the transcription and expression levels of Nrf2 were up-regulated in SVCV-infected EPC cells with the unknown mechanism(s)...
September 28, 2016: Fish & Shellfish Immunology
Katarzyna Lubelska, Katarzyna Wiktorska, Lidia Mielczarek, Małgorzata Milczarek, Ilona Zbroińska-Bregisz, Zdzisław Chilmonczyk
Sulforaphane (SFN), a naturally occurring chemopreventive and anticancer agent, is a nuclear factor, erythroid 2-like 2 (NFE2L2/Nrf2) inducer. Nrf2 plays a critical role in coordinating the cell defense system by initiating the transcription of cytoprotective genes, including detoxification enzymes such as NAD(P)H quinone dehydrogenase 1 (NQO1) and transport proteins such as ATP-binding cassette, subfamily C (CFTR/MRP). Recently, the essential role of Nrf2 in tumor development and progression and in the development of multidrug resistance in cancer cells has been highlighted...
September 16, 2016: Nutrition and Cancer
Jamie L Lim, Susanne M A van der Pol, Wia Baron, Joe M McCord, Helga E de Vries, Jack van Horssen
Oligodendrocyte damage and loss are key features of multiple sclerosis (MS) pathology. Oligodendrocytes appear to be particularly vulnerable to reactive oxygen species (ROS) and cytokines, such as tumor necrosis factor-α (TNF), which induce cell death and prevent the differentiation of oligodendrocyte progenitor cells (OPCs). Here, we investigated the efficacy of sulforaphane (SFN), monomethyl fumarate (MMF) and Protandim to induce Nrf2-regulated antioxidant enzyme expression, and protect oligodendrocytes against ROS-induced cell death and ROS-and TNF-mediated inhibition of OPC differentiation...
September 7, 2016: Antioxidants (Basel, Switzerland)
Li Kong, Bo Liu, Chenghong Zhang, Bing Wang, Hongfei Wang, Xiaoxia Song, Yang Yang, Xiang Ren, Liangwei Yin, Hui Kong, Haiying Ma
Oxidative stress due to excessive light exposure can exacerbate a variety of human retinal diseases by accelerating photoreceptor cell death. The thioredoxin (Trx) system is considered to play a crucial role in reduction/oxidation (redox) regulation of signal transduction and in cell defense against oxidative stresses. Sulforaphane (SF) protects cells from oxidative damage through nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is responsible for multiple detoxification processes, including elevating the expression of Trx...
August 25, 2016: Neurochemistry International
Qian Zhou, Bin Chen, Xindong Wang, Lixin Wu, Yang Yang, Xiaolan Cheng, Zhengli Hu, Xueting Cai, Jie Yang, Xiaoyan Sun, Wuguang Lu, Huaijiang Yan, Jiao Chen, Juan Ye, Jianping Shen, Peng Cao
Sulforaphane, a naturally occurring compound found in cruciferous vegetables, has been shown to be neuroprotective in several neurological disorders. In this study, we sought to investigate the potential protective effects and associated molecular mechanisms of sulforaphane in an in vivo Parkinson's disease (PD) model, based on rotenone-mediated neurotoxicity. Our results showed that sulforaphane inhibited rotenone-induced locomotor activity deficiency and dopaminergic neuronal loss. Additionally, sulforaphane treatment inhibited the rotenone-induced reactive oxygen species production, malondialdehyde (MDA) accumulation, and resulted in an increased level of total glutathione and reduced glutathione (GSH): oxidized glutathione (GSSG) in the brain...
2016: Scientific Reports
Sona Hudecova, Jana Markova, Veronika Simko, Lucia Csaderova, Tibor Stracina, Marta Sirova, Michaela Fojtu, Eliska Svastova, Paulina Gronesova, Michal Pastorek, Marie Novakova, Dana Cholujova, Juraj Kopacek, Silvia Pastorekova, Jan Sedlak, Olga Krizanova
In this study we show that anti-tumor effect of sulforaphane (SFN) is partially realized through the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). This effect was verified in vitro on three different stable cell lines and also in vivo on the model of nude mice with developed tumors. Early response (6 hours) of A2780 ovarian carcinoma cells to SFN treatment involves generation of mitochondrial ROS and increased transcription of NRF2 and its downstream regulated genes including heme oxygenase 1, NAD(P)H:quinine oxidoreductase 1, and KLF9...
April 25, 2016: Oncotarget
Wei Yao, Ji-Chun Zhang, Tamaki Ishima, Chao Dong, Chun Yang, Qian Ren, Min Ma, Mei Han, Jin Wu, Hiroyuki Suganuma, Yusuke Ushida, Masayuki Yamamoto, Kenji Hashimoto
The transcription factor Keap1-Nrf2 system plays a key role in inflammation which is involved in depression. We found lower expression of Keap1 and Nrf2 proteins in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of hippocampus in mice with depression-like phenotype compared to control mice. Serum levels of pro-inflammatory cytokines in Nrf2 knock-out (KO) mice were higher than those of wild-type mice, suggestive of enhanced inflammation in KO mice. Decreased brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-receptor-kinase B (TrkB) signaling in the PFC, CA3 and DG plays a role in the depression-like phenotype of Nrf2 KO mice...
2016: Scientific Reports
Zheng Xu, Shudong Wang, Honglei Ji, Zhiguo Zhang, Jing Chen, Yi Tan, Kupper Wintergerst, Yang Zheng, Jian Sun, Lu Cai
To develop a clinic-relevant protocol for systemic up-regulation of NFE2-related factor 2 (Nrf2) to prevent diabetic cardiomyopathy (DCM), male db/db and age-matched wild-type (WT) mice were given sulforaphane (SFN, an Nrf2 activator) and its natural source, broccoli sprout extract (BSE) by gavage every other day for 3 months, with four groups: vehicle (0.1 ml/10 g), BSE-low dose (estimated SFN availability at 0.5 mg/kg), BSE-high dose (estimated SFN availability at 1.0 mg/kg), and SFN (0.5 mg/kg)...
2016: Scientific Reports
Aixian Lan, Wenjun Li, Yao Liu, Zhaohui Xiong, Xinyan Zhang, Shanshan Zhou, Olesya Palko, Hao Chen, Mayanga Kapita, Justin R Prigge, Edward E Schmidt, Xin Chen, Zheng Sun, Xiaoxin Luke Chen
Oxidative stress is known to play an important role in oral cancer development. In this study we aimed to examine whether a chemical activator of NRF2, sulforaphane (SFN), may have chemopreventive effects on oxidative stress-associated oral carcinogenesis. We first showed that Nrf2 activation and oxidative damage were commonly seen in human samples of oral leukoplakia. With gene microarray and immunostaining, we found 4-nitroquinoline 1-oxide (4NQO) in drink activated the Nrf2 pathway and produced oxidative damage in mouse tongue...
July 15, 2016: Oncotarget
Chong Liu, Huan Xu, Shi Fu, Yanbo Chen, Qi Chen, Zhikang Cai, Juan Zhou, Zhong Wang
Purpose. We evaluated the effect of sulforaphane (SFN) treatment on the function and changes of expression of Nrf2-ARE pathway in the bladder of rats with bladder outlet obstruction (BOO). Materials and Methods. A total of 18 male Sprague-Dawley rats at age of 8 weeks were divided into 3 groups (6 of each): the sham operated group, the BOO group, and the BOO+SFN group. We examined histological alterations and the changes of oxidative stress markers and the protein expression of the Nrf2-ARE pathway. Results...
2016: Oxidative Medicine and Cellular Longevity
Marta Pajares, Natalia Jiménez-Moreno, Ángel J García-Yagüe, Maribel Escoll, María L de Ceballos, Fred Van Leuven, Alberto Rábano, Masayuki Yamamoto, Ana I Rojo, Antonio Cuadrado
Autophagy is a highly coordinated process that is controlled at several levels including transcriptional regulation. Here, we identify the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) as a regulator of autophagy gene expression and its relevance in a mouse model of Alzheimer disease (AD) that reproduces impaired APP (amyloid beta precursor protein) and human (Hs)MAPT/TAU processing, clearance and aggregation. We screened the chromatin immunoprecipitation database ENCODE for 2 proteins, MAFK and BACH1 that bind the NFE2L2-regulated enhancer antioxidant response element (ARE)...
July 18, 2016: Autophagy
Paul M Holloway, Scarlett Gillespie, Felix Becker, Shantel A Vital, Victoria Nguyen, J Steven Alexander, Paul C Evans, Felicity N E Gavins
Sepsis is often characterized by an acute brain inflammation and dysfunction, which is associated with increased morbidity and mortality worldwide. Preventing cerebral leukocyte recruitment may provide the key to halt progression of systemic inflammation to the brain. Here we investigated the influence of the anti-inflammatory and anti-oxidant compound, sulforaphane (SFN) on lipopolysaccharide (LPS)-induced cellular interactions in the brain. The inflammatory response elicited by LPS was blunted by SFN administration (5 and 50mg/kg i...
October 2016: Vascular Pharmacology
Julie E Bauman, Yan Zang, Malabika Sen, Changyou Li, Lin Wang, Patricia A Egner, Jed W Fahey, Daniel P Normolle, Jennifer R Grandis, Thomas W Kensler, Daniel E Johnson
Chronic exposure to carcinogens represents the major risk factor for head and neck squamous cell carcinoma (HNSCC). Beverages derived from broccoli sprout extracts (BSE) that are rich in glucoraphanin and its bioactive metabolite sulforaphane promote detoxication of airborne pollutants in humans. Herein, we investigated the potential chemopreventive activity of sulforaphane using in vitro models of normal and malignant mucosal epithelial cells and an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO)...
July 2016: Cancer Prevention Research
Yao-Wu Liu, Ya-Qin Cheng, Xiao-Li Liu, Yun-Chao Hao, Yu Li, Xia Zhu, Fan Zhang, Xiao-Xing Yin
Mangiferin, a natural C-glucoside xanthone, has anti-inflammatory, anti-oxidative, neuroprotective actions. Our previous study showed that mangiferin could attenuate diabetes-associated cognitive impairment of rats by enhancing the function of glyoxalase 1 (Glo-1) in brain. The aim of this study was to investigate whether Glo-1 upregulation by mangiferin in central neurons exposed to chronic high glucose may be related to activation of Nrf2/ARE pathway. Compared with normal glucose (25 mmol/L) culture, Glo-1 protein, mRNA, and activity levels were markedly decreased in primary hippocampal and cerebral cortical neurons cultured with high glucose (50 mmol/L) for 72 h, accompanied by the declined Nrf2 nuclear translocation and protein expression of Nrf2 in cell nucleus, as well as protein expression and mRNA level of γ-glutamylcysteine synthetase (γ-GCS) and superoxide dismutase activity, target genes of Nrf2/ARE signaling...
June 18, 2016: Molecular Neurobiology
Claudia Stolt, Imke H E Schmidt, Yana Sayfart, Ivo Steinmetz, Antje Bast
The environmental bacterium and potential biothreat agent Burkholderia pseudomallei causes melioidosis, an often fatal infectious disease. Increased serum bilirubin has been shown to be a negative predictive factor in melioidosis patients. We therefore investigated the role of heme oxygenase-1 (HO-1), which catalyzes the degradation of heme into the bilirubin precursor biliverdin, ferrous iron, and CO during B. pseudomallei infection. We found that infection of murine macrophages induces HO-1 expression, involving activation of several protein kinases and the transcription factor nuclear erythroid-related factor 2 (Nrf2)...
August 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yuji Fuse, Vu Thanh Nguyen, Makoto Kobayashi
Transcription factor Nrf2 induces a number of detoxifying enzymes and antioxidant proteins to confer protection against the toxic effects of a diverse range of chemicals including inorganic arsenicals. Although a number of studies using cultured cells have demonstrated that Nrf2 has a cell-protective function against acute and high-dose arsenic toxicity, there is no clear in vivo evidence of this effect. In the present study, we genetically investigated the protective role of Nrf2 against acute sodium arsenite toxicity using the zebrafish Nrf2 mutant, nrf2a(fh318)...
August 15, 2016: Toxicology and Applied Pharmacology
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