scholarly journals The Integrative Role of Sulforaphane in Preventing Inflammation, Oxidative Stress and Fatigue: A Review of a Potential Protective Phytochemical

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 521 ◽  
Author(s):  
Ruheea Taskin Ruhee ◽  
Katsuhiko Suzuki
Keyword(s):  
Oxidative Stress ◽  
Nuclear Translocation ◽  
Gene Activation ◽  
Organ Damage ◽  
Bioactive Molecules ◽  
Cruciferous Vegetables ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Target Gene

Cruciferous vegetables hold a myriad of bioactive molecules that are renowned for possessing unique medicinal benefits. Sulforaphane (SFN) is one of the potential nutraceuticals contained within cruciferous vegetables that is useful for improving health and diseased conditions. The objective of this review is to discuss the mechanistic role for SFN in preventing oxidative stress, fatigue, and inflammation. Direct and indirect research evidence is reported to identify the nontoxic dose of SFN for human trials, and effectiveness of SFN to attenuate inflammation and/or oxidative stress. SFN treatment modulates redox balance via activating redox regulator nuclear factor E2 factor-related factor (Nrf2). SFN may play a crucial role in altering the Keap1/Nrf2/ARE pathway (an intricate response to many stimuli or stress), which induces Nrf2 target gene activation to reduce oxidative stress. In addition, SFN reduces inflammation by suppressing centrally involved inflammatory regulator nuclear factor-kappa B (NF-κB), which in turn downregulates the expression of proinflammatory cytokines and mediators. Exercise may induce a significant range of fatigue, inflammation, oxidative stress, and/or organ damage due to producing excessive reactive oxygen species (ROS) and inflammatory cytokines. SFN may play an effective role in preventing such damage via inducing phase 2 enzymes, activating the Nrf2/ARE signaling pathway or suppressing nuclear translocation of NF-κB. In this review, we summarize the integrative role of SFN in preventing fatigue, inflammation, and oxidative stress, and briefly introduce the history of cruciferous vegetables and the bioavailability and pharmacokinetics of SFN reported in previous research. To date, very limited research has been conducted on SFN’s effectiveness in improving exercise endurance or performance. Therefore, more research needs to be carried out to determine the effectiveness of SFN in the field of exercise and lifestyle factors.

scholarly journals Protective Effects of GYY4137 on Renal Ischaemia/Reperfusion Injury through Nrf2-Mediated Antioxidant Defence

2021 ◽  
pp. 1-9
Author(s):  
Hongmei Zhao ◽  
Yun Qiu ◽  
Yichen Wu ◽  
Hong Sun ◽  
Sumin Gao
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Nuclear Translocation ◽  
Organ Damage ◽  
Related Factor ◽  
Protective Effects ◽  
Ischaemia Reperfusion Injury ◽  
Renal Ischaemia ◽  
Ischaemia Reperfusion ◽  
Renal Histology

<b><i>Introduction/Aims:</i></b> Hydrogen sulfide (H<sub>2</sub>S) is considered to be the third most important endogenous gasotransmitter in organisms. GYY4137 is a long-acting donor for H<sub>2</sub>S, a gas transmitter that has been shown to prevent multi-organ damage in animal studies. We previously reported the effect of GYY4137 on cardiac ischaemia reperfusion injury (IRI) in diabetic mice. However, the role and mechanism of GYY4137 in renal IRI are poorly understood. The aims of this study were to determine whether GYY4137 can effectively alleviate the injury induced by renal ischaemia reperfusion and to explore its possible mechanism. <b><i>Methods:</i></b> Mice received right nephrectomy and clipping of the left renal pedicle for 45 min. GYY4137 was administered by intraperitoneal injection for 2 consecutive days before the operation. The model of hypoxia/reoxygenation injury was established in HK-2 cells, which were pre-treated with or without GYY4137. Renal histology, function, apoptosis, and oxidative stress were measured. Western blot was used to measure the target ­protein after renal IRI. <b><i>Results:</i></b> The results indicated that GYY4137 had a clear protective effect on renal IRI as reflected by the attenuation of renal dysfunction, renal tubule injury, and apoptosis. Moreover, GYY4137 remarkably reduced renal IRI-induced oxidative stress. GYY4137 significantly elevated the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2) and the expression of antioxidant enzymes regulated by Nrf2, including SOD, HO-1, and NQO-1. <b><i>Conclusions:</i></b> GYY4137 alleviates ischaemia reperfusion-induced renal injury through activating the antioxidant effect mediated by Nrf2 signalling.

scholarly journals Anti-Carcinogenic Glucosinolates in Cruciferous Vegetables and Their Antagonistic Effects on Prevention of Cancers

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2983 ◽  
Author(s):  
Prabhakaran Soundararajan ◽  
Jung Kim
Keyword(s):  
Antagonistic Activity ◽  
Antagonistic Effect ◽  
Side Chain ◽  
Cruciferous Vegetables ◽  
Related Factor ◽  
Nuclear Factor ◽  
Naturally Occurring ◽  
Therapeutic Properties ◽  
Responsive Element

Glucosinolates (GSL) are naturally occurring β-d-thioglucosides found across the cruciferous vegetables. Core structure formation and side-chain modifications lead to the synthesis of more than 200 types of GSLs in Brassicaceae. Isothiocyanates (ITCs) are chemoprotectives produced as the hydrolyzed product of GSLs by enzyme myrosinase. Benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane ([1-isothioyanato-4-(methyl-sulfinyl) butane], SFN) are potential ITCs with efficient therapeutic properties. Beneficial role of BITC, PEITC and SFN was widely studied against various cancers such as breast, brain, blood, bone, colon, gastric, liver, lung, oral, pancreatic, prostate and so forth. Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor limits the tumor progression. Induction of ARE (antioxidant responsive element) and ROS (reactive oxygen species) mediated pathway by Nrf2 controls the activity of nuclear factor-kappaB (NF-κB). NF-κB has a double edged role in the immune system. NF-κB induced during inflammatory is essential for an acute immune process. Meanwhile, hyper activation of NF-κB transcription factors was witnessed in the tumor cells. Antagonistic activity of BITC, PEITC and SFN against cancer was related with the direct/indirect interaction with Nrf2 and NF-κB protein. All three ITCs able to disrupts Nrf2-Keap1 complex and translocate Nrf2 into the nucleus. BITC have the affinity to inhibit the NF-κB than SFN due to the presence of additional benzyl structure. This review will give the overview on chemo preventive of ITCs against several types of cancer cell lines. We have also discussed the molecular interaction(s) of the antagonistic effect of BITC, PEITC and SFN with Nrf2 and NF-κB to prevent cancer.

scholarly journals Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases

2019 ◽  
Vol 20 (13) ◽  
pp. 3208 ◽  
Author(s):  
Fabiane Valentini Francisqueti-Ferron ◽  
Artur Junio Togneri Ferron ◽  
Jéssica Leite Garcia ◽  
Carol Cristina Vágula de Almeida Silva ◽  
Mariane Róvero Costa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcriptional Factor ◽  
Future Research ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Age Related ◽  
Basic Concepts

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

scholarly journals The Role of Nrf2 in Hearing Loss

2021 ◽  
Vol 12 ◽  
Author(s):  
Dafei Li ◽  
Haiyan Zhao ◽  
Zhong-Kai Cui ◽  
Guangyong Tian
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Cell Damage ◽  
Hearing Protection ◽  
Related Factor ◽  
Nuclear Factor ◽  
The World ◽  
Hair Cell Damage ◽  
Heavy Burden

Hearing loss is a major unresolved problem in the world, which has brought a heavy burden to society, economy, and families. Hair cell damage and loss mediated by oxidative stress are considered to be important causes of hearing loss. The nuclear factor erythroid 2–related factor 2 (Nrf2) is a major regulator of antioxidant capacity and is involved in the occurrence and development of a series of toxic and chronic diseases associated with oxidative stress. In recent years, studies on the correlation between hearing loss and Nrf2 target have continuously broadened our knowledge, and Nrf2 has become a new strategic target for the development and reuse of hearing protection drugs. This review summarized the correlation of Nrf2 in various types of hearing loss, and the role of drugs in hearing protection through Nrf2 from the literature.

scholarly journals Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 198 ◽  
Author(s):  
Ba-Wool Lee ◽  
Ji-Hye Ha ◽  
Han-Gyo Shin ◽  
Seong-Hun Jeong ◽  
Da-Bin Jeon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Herbal Remedy ◽  
Related Factor ◽  
Nuclear Factor ◽  
Tnf Α

Spiraea prunifolia var. simpliciflora (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1β, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1β, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.

scholarly journals Anemopsis californica Attenuates Photoaging by Regulating MAPK, NRF2, and NFATc1 Signaling Pathways

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1882
Author(s):  
Quynh T. N. Nguyen ◽  
Minzhe Fang ◽  
Nhung Quynh Do ◽  
Jeehaeng Jeong ◽  
Sarang Oh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Biological Effects ◽  
Dermal Fibroblasts ◽  
Related Factor ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Anemopsis Californica

Long-term exposure of the skin to solar radiation causes chronic inflammation and oxidative stress, which accelerates collagen degradation. This contributes to the formation of wrinkles and dark spots, skin fragility, and even skin cancer. In this study, Anemopsis californica (AC), a herb from North America that is well known for treating microorganism infection and promoting wound healing, was investigated for its photoprotective effects. The biological effects of AC were studied on two in vitro models, namely, lipopolysaccharide (LPS)-induced macrophages and ultraviolet B (UVB)-irradiated dermal fibroblasts, to characterize its underlying molecular mechanisms. The results showed that AC decreased the mRNA levels of inflammatory mediators in sensitized macrophages, including cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Moreover, AC alleviated UVB-induced photoaging in dermal fibroblasts by restoring procollagen synthesis. This resulted from the regulation of excessive reactive oxygen species (ROS) by AC, which was mediated by the activation of the antioxidative system nuclear factor erythroid 2-related factor 2 (NRF2). AC also alleviated oxidative stress and inflammatory responses by inhibiting the phosphorylation of mitogen-activated protein kinase (MAPK) and interfering with the nuclear translocation of the immune regulator nuclear factor of activated T-cells 1 (NFATc1). In conclusion, the protective effects of AC on skin cellular components suggested that it has the potential for use in the development of drugs and cosmetics that protect the skin from UVB-induced chronic inflammation and aging.

scholarly journals SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy

2018 ◽  
Vol 60 (2) ◽  
pp. 145-157 ◽  
Author(s):  
Huan Zhang ◽  
Xiuxia Liu ◽  
Shanshan Zhou ◽  
Ye Jia ◽  
Ying Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
Critical Role ◽  
Antioxidant Defense System ◽  
Related Factor ◽  
Diabetic Mice ◽  
Nrf2 Protein

c-Jun N-terminal kinase (JNK) contributes to the pathogenesis of diabetic nephropathy (DN). The JNK inhibitor SP600125 was reported to ameliorate DN. However, the mechanism remained unclear. We previously reported that SP600125 activated nuclear factor erythroid 2-related factor 2 (NRF2), a governor of the cellular antioxidant defense system, in the aortas of the diabetic mice. Given the critical role of NRF2 in preventing DN, the present study aimed to test whether or not NRF2 is required for SP600125’s protection against DN. To test the role of NRF2 in SP600125’s effect, streptozotocin-induced C57BL/6 wild-type (WT) and Nrf2-knockout (KO) diabetic mice were treated in the presence or absence of SP600125, for 24 weeks. To explore the mechanism by which SP600125 activates NRF2, mouse mesangial cells (MMCs) were treated with high glucose (HG), in the presence or absence of either SP600125 or JNK siRNA. SP600125 significantly attenuated the diabetes-induced renal oxidative stress, inflammation, fibrosis, pathological change and dysfunction in the WT, but not the Nrf2 KO mice. SP600125 inactivated JNK, inhibited kelch-like ECH-associated protein 1 expression, preserved NRF2 protein and facilitated its nuclear translocation in the kidneys of the WT mice, the effects of which were similarly produced by either SP600125 or JNK siRNA in HG-treated MMCs. Further, both SP600125 and JNK siRNA alleviated HG-induced mesangial oxidative stress and expression of inflammatory and fibrotic genes. The present study demonstrates that NRF2 is required for SP600125’s protection against DN. SP600125 activates NRF2 possibly via inhibition of JNK-induced Keap1 expression.

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