Cited by 1,200Genomics, phytochemicals, and oxidative stressNF-κB Signaling PathwaysRedox biology and oxidative stress

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Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways

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Wardyn, Joanna D., Ponsford, Amy H., Sanderson, Christopher M.·2015·Biochemical Society Transactions

DOI 10.1042/bst20150014PMC PMC4613495

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Abstract

In most tissues, cells are exposed to frequent changes in levels of oxidative stress and inflammation. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor-κB (NF-κB) are the two key transcription factors that regulate cellular responses to oxidative stress and inflammation respectively. Pharmacological and genetic studies suggest that there is functional cross-talk between these two important pathways. The absence of Nrf2 can exacerbate NF-κB activity leading to increased cytokine production, whereas NF-κB can modulate Nrf2 transcription and activity, having both positive and negative effects on the target gene expression. This review focuses on the potentially complex molecular mechanisms that link the Nrf2 and NF-κB pathways and the importance of designing more effective therapeutic strategies to prevent or treat a broad range of neurological disorders.

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Background
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Background
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Background
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Background
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Background
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Background
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Background
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Background
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Background
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Background
Walnut (Juglans regia L.) Septum: Assessment of Bioactive Molecules and In Vitro Biological Effects
Rusu, M. E., Fizeșan, I., Pop, A., Mocan, A., Gheldiu, A.-M., Babotă, M., Vodnar, D. C., Jurj, A. M., Berindan‐Neagoe, I., Vlase, L., et al. (2020) · Molecules · doi:10.3390/molecules25092187 · Cited by 70
Targeting Nrf2/HO-1 anti-oxidant signaling pathway in the progression of multiple sclerosis and influences on neurological dysfunctions
Upadhayay, S., & Mehan, S. (2021) · Brain Disorders · doi:10.1016/j.dscb.2021.100019 · Cited by 72
Pistachio hull polysaccharide protects Nile tilapia against LPS-induced excessive inflammatory responses and oxidative stress, possibly via TLR2 and Nrf2 signaling pathways
Mohammadi, G., Karimi, A. A., Hafezieh, M., Dawood, M. A. O., & Abo‐Al‐Ela, H. G. (2021) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2021.12.042 · Cited by 70
Multiple mechanisms of dimethyl fumarate in amyloid β‐induced neurotoxicity in human neuronal cells
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Gamma-oryzanol Prevents LPS-induced Brain Inflammation and Cognitive Impairment in Adult Mice
Mastinu, A., Bonini, S. A., Rungratanawanich, W., Aria, F., Marziano, M., Maccarinelli, G., Abate, G., Premoli, M., Memo, M., & Uberti, D. L. (2019) · Nutrients · doi:10.3390/nu11040728 · Cited by 72
“Moreover, Nrf2-dependent HO-1 increased expression inhibits NF-κB p65 activity [59].”
Background
Acetyl-11-keto-β-boswellic acid ameliorates cognitive deficits and reduces amyloid-β levels in APPswe/PS1dE9 mice through antioxidant and anti-inflammatory pathways
Wei, C., Fan, J. J., Sun, X., Yao, J., Guo, Y., Zhou, B., & Shang, Y. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.02.022 · Cited by 73
Gallic acid suppresses inflammation and oxidative stress through modulating Nrf2-HO-1-NF-κB signaling pathways in elastase-induced emphysema in rats
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The NRF-2/HO-1 Signaling Pathway: A Promising Therapeutic Target for Metabolic Dysfunction-Associated Steatotic Liver Disease
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“148,149 During this process, the Nrf2/HO-1 pathway plays a crucial role by reducing ROS levels through the inhibition of hepatic oxidative stress.”
Background
Anti-inflammatory Activity of 8-Hydroxydaidzein in LPS-Stimulated BV2 Microglial Cells via Activation of Nrf2-Antioxidant and Attenuation of Akt/NF-κB-Inflammatory Signaling Pathways, as Well As Inhibition of COX-2 Activity
Wu, P.-S., Ding, H., Yen, J.-H., Chen, S.-F., Lee, K., & Wu, M. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b00437 · Cited by 70
Sodium butyrate inhibits high cholesterol-induced neuronal amyloidogenesis by modulating NRF2 stabilization-mediated ROS levels: involvement of NOX2 and SOD1
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The Role of Free Radicals in Autophagy Regulation: Implications for Ageing
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“Free KEAP1 can prevent IKK from binding to heat shock protein 90 (Hsp90) [106] thereby inducing autophagic degradation of IKK and attenuating NFκB signalling [107].”
Background
Bioactive Compounds as Inhibitors of Inflammation, Oxidative Stress and Metabolic Dysfunctions via Regulation of Cellular Redox Balance and Histone Acetylation State
Kang, H., & Kim, B. (2023) · Foods · doi:10.3390/foods12050925 · Cited by 74
“Moreover, the pro-inflammatory transcription factor NF-κB can increase the recruitment of HDAC to the antioxidant response element (ARE) with the concomitant interference of NRF2 transcription [40,41].”
Background
Oxidative stress and inflammation induced by air pollution-derived PM2.5 persist in the lungs of mice after cessation of their sub-chronic exposure
Barbier, E., Carpentier, J., Simonin, O., Gosset, P., Platel, A., Happillon, M., Alleman, L., Perdrix, E., Riffault, V., Chassat, T., et al. (2023) · Environment International · doi:10.1016/j.envint.2023.108248 · Cited by 67
Sunflower seed-derived bioactive peptides show antioxidant and anti-inflammatory activity: From in silico simulation to the animal model
Tonolo, F., Coletta, S., Fiorese, F., Grinzato, A., Albanesi, M., Folda, A., Ferro, S., Mario, A. D., Piazza, I., Mammucari, C., et al. (2023) · Food Chemistry · doi:10.1016/j.foodchem.2023.138124 · Cited by 66
Dietary Astaxanthin: A Promising Antioxidant and Anti-Inflammatory Agent for Brain Aging and Adult Neurogenesis
Medoro, A., Davinelli, S., Milella, L., Willcox, B. J., Allsopp, R., Scapagnini, G., & Willcox, D. C. (2023) · Marine Drugs · doi:10.3390/md21120643 · Cited by 73
“Numerous studies have additionally shown that the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κ B) signaling network, the main pathway involved in the control of inflammatory responses, and the Nrf2 system interact [35].”
Background
Nuclear Factor–Erythroid-2–Related Factor 2 in Aging and Lung Fibrosis
Swamy, S., Rajasekaran, N. S., & Thannickal, V. J. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.02.022 · Cited by 67
Transcription Factor KLF2 and Its Role in the Regulation of Inflammatory Processes
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Cyanidin Chloride Induces Apoptosis by Inhibiting NF-κB Signaling through Activation of Nrf2 in Colorectal Cancer Cells
Lee, D.-Y., Yun, S., Song, M.-Y., Jung, K., & Kim, E. (2020) · Antioxidants · doi:10.3390/antiox9040285 · Cited by 66
“Recent studies suggest that there is functional crosstalk between the Nrf2 pathway and NF-κB signaling [25].”
Background
Galangin ameliorates Imiquimod-Induced psoriasis-like skin inflammation in BALB/c mice via down regulating NF-κB and activation of Nrf2 signaling pathways
Sangaraju, R., Alavala, S., Nalban, N., Jerald, M. K., & Sistla, R. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107754 · Cited by 66
Oxidative Stress Signaling Mediated Pathogenesis of Diabetic Cardiomyopathy
Tang, Z., Wang, P., Dong, C., Zhang, J., Wang, X., & Pei, H. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5913374 · Cited by 73
“In reverse, Nrf2 can be inhibited by p65 activity, and its mechanism is a competition for the transcriptional coactivator CREB-binding protein(CBP-) p300 complex [39].”
Background
Ellagic acid protects mice against sleep deprivation-induced memory impairment and anxiety by inhibiting TLR4 and activating Nrf2
Wang, W., Yang, L., Liu, T., Wang, J., Wen, A., & Ding, Y. (2020) · Aging · doi:10.18632/aging.103270 · Cited by 66
“In addition, studies have shown that crosstalk between Nrf2 and NFκB reliant signaling regulates inflammation [31, 33].”
Background
Targeting NRF2–KEAP1 axis by Omega-3 fatty acids and their derivatives: Emerging opportunities against aging and diseases
Davinelli, S., Medoro, A., Intrieri, M., Saso, L., Scapagnini, G., & Kang, J. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.11.017 · Cited by 72
Effect of dimethyl fumarate on neuroinflammation and apoptosis in pentylenetetrazol kindling model in rats
Singh, N., Saha, L., Kumari, P., Singh, J., Bhatia, A., Banerjee, D., & Chakrabarti, A. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.11.013 · Cited by 65
Mitochondrial alterations triggered by repeated exposure to fine (PM2.5-0.18) and quasi-ultrafine (PM0.18) fractions of ambient particulate matter
Sotty, J., Kluza, J., Sousa, C. D., Tardivel, M., Anthérieu, S., Alleman, L., Canivet, L., Perdrix, E., Loyens, A., Marchetti, P., et al. (2020) · Environment International · doi:10.1016/j.envint.2020.105830 · Cited by 71
JNK‐IN‐8, a c‐Jun N‐terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke
Zheng, J., Dai, Q., Han, K., Hong, W., Jia, D., Mo, Y., Lv, Y., Tang, H., Fu, H., & Geng, W. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29183 · Cited by 74
Protective effect of galangin against dextran sulfate sodium (DSS)-induced ulcerative colitis in Balb/c mice
Sangaraju, R., Nalban, N., Alavala, S., Rajendran, V., Jerald, M. K., & Sistla, R. (2019) · Inflammation Research · doi:10.1007/s00011-019-01252-w · Cited by 64
Role of Nrf2 in rheumatoid arthritis
Chadha, S., Behl, T., Kumar, A., Khullar, G., & Arora, S. (2020) · Current Research in Translational Medicine · doi:10.1016/j.retram.2020.05.002 · Cited by 65
Dihydromyricetin reverses MRP2-induced multidrug resistance by preventing NF-κB-Nrf2 signaling in colorectal cancer cell
Wang, Z., Sun, X., Feng, Y., Wang, Y., Zhang, L., Wang, Y., Fang, Z. Y., Azami, N. L. B., Sun, M., & Li, Q. (2020) · Phytomedicine · doi:10.1016/j.phymed.2020.153414 · Cited by 64
The Role of NRF2 in Obesity-Associated Cardiovascular Risk Factors
Gutiérrez‐Cuevas, J., Galicia‐Moreno, M., Monroy-Ramírez, H. C., Sandoval-Rodriguez, A. S., Garcia-Bañuelos, J. J., Santos, A., & Armendáriz‐Borunda, J. (2022) · Antioxidants · doi:10.3390/antiox11020235 · Cited by 67
Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice
Çağlayan, B., Kılıç, E., Dalay, A., Altunay, S., Tuzcu, M., Erten, F., Orhan, C., Günal, M. Y., Yuluğ, B., Juturu, V., et al. (2018) · Molecular Biology Reports · doi:10.1007/s11033-018-4465-4 · Cited by 64
Host modulation therapy using anti-inflammatory and antioxidant agents in periodontitis: A review to a clinical translation
Sulijaya, B., Takahashi, N., & Yamazaki, K. (2019) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2019.07.002 · Cited by 65
Modulation of SIRT1-mediated signaling cascades in the liver contributes to the amelioration of nonalcoholic steatohepatitis in high fat fed middle-aged LDL receptor knockout mice by dihydromyricetin
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Isoliquiritigenin prevents Doxorubicin-induced hepatic damage in rats by upregulating and activating SIRT1
Al-Qahtani, W. H., Alshammari, G. M., Ajarem, J. S., Al-Zahrani, A. Y., Alzuwaydi, A., Eid, R. A., & Yahya, M. A. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112594 · Cited by 64
Mechanisms of Action of Ozone Therapy in Emerging Viral Diseases: Immunomodulatory Effects and Therapeutic Advantages With Reference to SARS-CoV-2
Cenci, A., Macchia, I., Sorsa, V. L., Sbarigia, C., Donna, V. D., & Pietraforte, D. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.871645 · Cited by 75
Modified citrus pectin ameliorates methotrexate-induced hepatic and pulmonary toxicity: role of Nrf2, galectin-3/TLR-4/NF-κB/TNF-α and TGF-β signaling pathways
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Background
Isothiocyanates Are Promising Compounds against Oxidative Stress, Neuroinflammation and Cell Death that May Benefit Neurodegeneration in Parkinson’s Disease
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The pivotal role of nuclear factor erythroid 2-related factor 2 in diabetes-induced endothelial dysfunction
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Bamboo Leaf Flavonoids Extracts Alleviate Oxidative Stress in HepG2 Cells via Naturally Modulating Reactive Oxygen Species Production and Nrf2-Mediated Antioxidant Defense Responses.
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“It is stressed that ROS production is often associated with the oxidative stress, and an increase in ROS production within cells indicates that the damage signaling occurred (West & Shadel, 2017).”
Background
Insights on the mechanisms of action of ozone in the medical therapy against COVID-19
Chirumbolo, S., Valdenassi, L., Simonetti, V., Bertossi, D., Ricevuti, G., Franzini, M., & Pandolfi, S. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107777 · Cited by 62
Hypoxia-Induced Neuroinflammation in Alzheimer’s Disease: Potential Neuroprotective Effects of Centella asiatica
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HYCO-3, a dual CO-releaser/Nrf2 activator, reduces tissue inflammation in mice challenged with lipopolysaccharide
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Sulforaphane Protects Cells against Lipopolysaccharide-Stimulated Inflammation in Murine Macrophages
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Authors: Wardyn, J. D., Ponsford, A. H., & Sanderson, C. M.
Affiliations: University of Liverpool (GB)
Corresponding author: Sanderson, Christopher M.
ORCID: Ponsford, Amy H.
Sanderson, Christopher M.
Venue: Biochemical Society Transactions
Publisher: Portland Press Ltd.
Published: 2015-08-01
Volume: 43
Issue: 4
Pages: 621-626
ISSN: 0300-5127 (ISSN-L)
1470-8752
DOI: 10.1042/bst20150014
PMC: PMC4613495
OpenAlex: W2133584350
Cited by: 1,200
References: 53
Citations by year: 2026: 139 · 2025: 131 · 2024: 117 · 2023: 145 · 2022: 165 · 2021: 154 · 2020: 124 · 2019: 95 · 2018: 68 · 2017: 44 · 2016: 15 · 2015: 1
FWCI: 4.09
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Biochemical Society Transactions (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust (096564/Z/11/Z)
Directorate for Biological Sciences
Biotechnology and Biological Sciences Research Council (1222890, BB/J014516/1)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: Nrf2, NF-κB, oxidative stress, inflammation, cytokine production, neurological disorders, treatment options
MeSH terms: Animals, Gene Expression Regulation, Humans, Nervous System Diseases, Signal Transduction, Cytokines, NF-kappa B, Oxidative Stress, NF-E2-Related Factor 2

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Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways

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