The DOI matches its Crossref record; 157 of the 159 references it cites were found in a registry or an index.
Neuroinflammation: Modulation by flavonoids and mechanisms of action
Abstract
Neuroinflammatory processes are known to contribute to the cascade of events culminating in the neuronal damage that underpins neurodegenerative disorders such as Parkinson's and Alzheimer's disease. Recently, there has been much interest in the potential neuroprotective effects of flavonoids, a group of plant secondary metabolites known to have diverse biological activity in vivo. With respect to the brain, flavonoids, such as those found in cocoa, tea, berries and citrus, have been shown to be highly effective in preventing age-related cognitive decline and neurodegeneration in both animals and humans. Evidence suggests that flavonoids may express such ability through a multitude of physiological functions, including an ability to modulate the brains immune system. This review will highlight the evidence for their potential to inhibit neuroinflammation through an attenuation of microglial activation and associated cytokine release, iNOS expression, nitric oxide production and NADPH oxidase activity. We will also detail the current evidence indicting that their regulation of these immune events appear to be mediated by their actions on intracellular signaling pathways, including the nuclear factor-κB (NF-κB) cascade and mitogen-activated protein kinase (MAPK) pathway. As such, flavonoids represent important precursor molecules in the quest to develop of a new generation of drugs capable of counteracting neuroinflammation and neurodegenerative disease.
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In the citing paper
“although it is widely proven that extended neuroinflammatory events can lead to the progressive neuronal damage described in many neurodegenerative diseases [70].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [70]
In the citing paper
“an inhibitory action against inducible nitric oxide synthase (iNOS) induction and subsequent NO production in response to glial activation”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [159]
In the citing paper
“an ability to inhibit the activation of NADPH oxidase and subsequent generation of ROS in activated glia”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [159]
In the citing paper
“an inhibitory role in the release of cytokines, such as IL-1β and TNF-α, from activated glia”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [159]
In the citing paper
“an inhibitory activity regulation of pro-inflammatory transcription factors such as nuclear factor (NF)-κB through the modulation of various glial and neuronal signaling pathways [158,159].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [159]
In the citing paper
“NF-κB is responsible for the activation of uncontrolled microglia, with subsequent ROS production, and pro-inflammatory cytokine and glutamate release, which in turn induce neuronal damage (Spencer et al., 2012).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Spencer et al., 2012
Citations
Cites
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Structure-antioxidant activity relationships of flavonoids and phenolic acids
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Mammalian MAP kinase signalling cascades
Chang, L., & Karin, M. (2001) · Nature · doi:10.1038/35065000 · Cited by 5,118
Nuclear Factor-κB — A Pivotal Transcription Factor in Chronic Inflammatory Diseases
Barnes, P. J., & Karin, M. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704103361506 · Cited by 4,622
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396
Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies
Manach, C., Williamson, G., Morand, C., Scalbert, A., & Rémésy, C. (2005) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.1.230s · Cited by 4,219 · cited 1×
“…pivotal in controlling neuronal resistance to neurotoxins, including oxidants (‘indirect’ antioxidant nature) (Levites et al., 2001) and inflammatory mediators (Spencer, 2009a), or through their chelation of transition metal ions such as iron (Levites et al., 2002; Mandel et al., 2005, 2006).”
BackgroundInteraction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor β
Kuiper, G. G. J. M., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., van der Saag, P. T., van der Burg, B., & Gustafsson, J.-Å. (1998) · Endocrinology · doi:10.1210/endo.139.10.6216 · Cited by 4,203
NF-κB regulation in the immune system
Li, Q., & Verma, I. M. (2002) · Nature Reviews Immunology · doi:10.1038/nri910 · Cited by 4,007
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580
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2 of the 159 references couldn’t be matched to a known paper.
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Important Flavonoids and Their Role as a Therapeutic Agent
Ullah, A., Munir, S., Badshah, S. L., Khan, N., Ghani, L., Poulson, B. G., Emwas, A.-H., & Jaremko, M. (2020) · Molecules · doi:10.3390/molecules25225243 · Cited by 1,696
Bioactive flavonoids in medicinal plants: Structure, activity and biological fate
Wang, T.-Y., Li, Q., & Bi, K.-S. (2017) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2017.08.004 · Cited by 1,022
Low-grade inflammation, diet composition and health: current research evidence and its translation
Minihane, A. M., Vinoy, S., Russell, W. R., Baka, A., Roche, H. M., Tuohy, K. M., Teeling, J. L., Blaak, E. E., Fenech, M. F., Vauzour, D., et al. (2015) · British Journal Of Nutrition · doi:10.1017/s0007114515002093 · Cited by 962
Rodriguez‐Mateos, A., Vauzour, D., Krueger, C. G., Shanmuganayagam, D., Reed, J. D., Calani, L., Mena, P. R., Rio, D. D., & Crozier, A. (2014) · Archives of Toxicology · doi:10.1007/s00204-014-1330-7 · Cited by 623
Williamson, G., Kay, C. D., & Crozier, A. (2018) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12351 · Cited by 620
Metadata
- Authors
- Spencer, J. P. E., Vafeiadou, K., Williams, R. J., & Vauzour, D.
- Affiliations
- University of Reading (GB)
- University of Bath (GB)
- University of East Anglia (GB)
- Corresponding author
- Spencer, Jeremy P.E.
- ORCID
- Vauzour, David
- Venue
- Molecular Aspects of Medicine
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 33
- Issue
- 1
- Pages
- 83-97
- ISSN
- 0098-2997 (ISSN-L)
- OpenAlex
- W1977122148
- Cited by
- 315
- References
- 159
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 21 · 2023: 29 · 2022: 23 · 2021: 20 · 2020: 30 · 2019: 25 · 2018: 18 · 2017: 26 · 2016: 27 · 2015: 21 · 2014: 25 · 2013: 13 · 2012: 17
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Aspects of Medicine (publishedVersion)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- University of Hertfordshire Research Archive (University of Hertfordshire) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/G005702/1, BB/E023185/1, BB/F008953/1, BB/C518222/1)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
- Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Keywords
- neuroinflammation, flavonoids, neuroprotection, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, microglial activation, cytokine production, nitric oxide, NADPH oxidase, inducible nitric oxide synthase, NF-κB signaling, MAPK signaling, intracellular signaling, age-related cognitive decline, Theobroma cacao, tea, berries, citrus
- MeSH terms
- Animals, Flavonoids, Humans, Inflammation, Nervous System Diseases, Signal Transduction, Neuroprotective Agents
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