Neuroinflammatory processes in cognitive disorders: Is there a role for flavonoids and n-3 polyunsaturated fatty acids in counteracting their detrimental effects?

Vauzour, David; Martinsen, Anneloes; Layé, Sophie

doi:10.1016/j.neuint.2015.08.004

Cited by 48 publications

(30 citation statements)

References 173 publications

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“…Of all these studies, 90% found a significant decrease of microglial density and/or activation after exposure to n-3 PUFAs, as a criterion for decreased neuroinflammation, whereas 10% could not find any effect (Orr et al, 2013;Vauzour et al, 2015;Trepanier et al, 2016;Nadjar et al, 2017). Moreover, we showed that the sourcing of PUFAs (from plants or dairy products) has a differential impact on LPS-modulating microglial phenotype (Dinel et al, 2016).…”

Section: Microglia As a Target For N-3 Pufas And Spmsmentioning

confidence: 57%

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Layé¹,

Nadjar²,

Joffre³

et al. 2017

Pharmacol Rev

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312

190

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Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain.

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Section: Microglia As a Target For N-3 Pufas And Spmsmentioning

confidence: 57%

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Layé¹,

Nadjar²,

Joffre³

et al. 2017

Pharmacol Rev

Self Cite

312

190

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“…Recently, much interest has focused on the suggested anti-inflammatory and neuroprotective effects of dietary derived polyphenols (Vauzour et al, 2015). We demonstrated that the flavonoid agathisflavone (bis-apigenin) reduces the neuroinflammation induced by glutamate, by modulating microglial activation and reducing the expression of pro-inflammatory cytokines TNF, IL6 and IL1β, and increasing the expression of anti-inflammatory markers.…”

Section: Discussionmentioning

confidence: 92%

Agathisflavone, a flavonoid derived from Poincianella pyramidalis (Tul.), enhances neuronal population and protects against glutamate excitotoxicity

et al. 2018

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Flavonoids are bioactive compounds that are known to be neuroprotective against glutamate-mediated excitotoxicity, one of the major causes of neurodegeneration. The mechanisms underlying these effects are unresolved, but recent evidence indicates flavonoids may modulate estrogen signaling, which can delay the onset and ameliorate the severity of neurodegenerative disorders. Furthermore, the roles played by glial cells in the neuroprotective effects of flavonoids are poorly understood. The aim of this study was to investigate the effects of the flavonoid agathisflavone (FAB) in primary neuron-glial co-cultures from postnatal rat cerebral cortex. Compared to controls, treatment with FAB significantly increased the number of neuronal progenitors and mature neurons, without increasing astrocytes or microglia. These pro-neuronal effects of FAB were suppressed by antagonists of estrogen receptors (ERα and ERβ). In addition, treatment with FAB significantly reduced cell death induced by glutamate and this was associated with reduced expression levels of pro-inflammatory (M1) microglial cytokines, including TNFα, IL1β and IL6, which are associated with neurotoxicity, and increased expression of IL10 and Arginase 1, which are associated with anti-inflammatory (M2) neuroprotective microglia. We also observed that FAB increased neuroprotective trophic factors, such as BDNF, NGF, NT4 and GDNF. The neuroprotective effects of FAB were also associated with increased expression of glutamate regulatory proteins in astrocytes, namely glutamine synthetase (GS) and Excitatory Amino Acid Transporter 1 (EAAT1). These findings indicate that FAB acting via estrogen signaling stimulates production of neurons in vitro and enhances the neuroprotective properties of microglia and astrocytes to significantly ameliorate glutamate-mediated neurotoxicity.

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“…DHM, a plant flavonoid, can cross the blood‐brain barrier and has anti‐inflammatory properties in vitro and in vivo . Recent research has suggested that flavonoids may be good candidates for modulating inflammation and preventing onset of neurodegenerative disorders . However, it is unknown whether DHM has anti‐inflammatory effects in AD.…”

Section: Discussionmentioning

confidence: 99%

“…Dihydromyricetin (DHM) is a plant flavonoid compound that is derived from the medicinal plant Ampelopsis grossedentata and has been demonstrated to be widely used in different therapeutic areas including antioxidative, anticancer, anti‐alcohol intoxication and so on . Substantial evidence has shown that flavonoids can cross the blood‐brain barrier, modulate inflammation, and exert neuroprotective effects . Previous studies have shown that DHM ameliorates behavioral deficits and reverses neuropathology of AD mainly by modulating GABA A Rs, which crucially involved in synaptic plasticity and made network excitability be decreased once activated in the brain, while abnormal network activity involving the loss of synapses leads to cognitive deficits in AD .…”

Section: Introductionmentioning

confidence: 99%

Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice

Feng

Wang

et al. 2018

CNS Neurosci Ther

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SummaryBackgroundActivated microglia‐mediated inflammation plays a key role in the pathogenesis of Alzheimer’s disease (AD). In addition, chronic activation of NLRP3 inflammasomes triggered by amyloid β peptide (Aβ) in microglia contributes to persistent neuroinflammation. Here, the primary goal was to assess whether Dihydromyricetin (DHM), a plant flavonoid compound, is effective therapies for AD; it is crucial to know whether DHM will affect microglial activation and neuroinflammation in APP/PS1 transgenic mice.MethodsAfter DHM was intraperitoneally injected in APP/PS1 double‐transgenic mice, we assessed the effect of DHM on microglial activation, the expression of NLRP3 inflammasome components, and the production of inflammatory cytokine IL‐1β by immunofluorescence and Western blot. To determine whether DHM play roles in the Aβ production and deposition, amyloid β protein precursor (APP) and β‐site APP cleaving enzyme1 (BACE1), as well as neprilysin (NEP), were detected by Western blot. Finally, behavior was tested by Morris Water Maze to illustrate whether DHM treatment has a significantly positive effect on ameliorating the memory and cognition deficits in AD.ResultsDihydromyricetin treatment significantly ameliorated memory and cognition deficits and decreased the number of activated microglia in the hippocampus and cortex of APP/PS1 mice. In addition, APP/PS1 mice show reduced activation of NLRP3 inflammasomes and reduced expression of NLRP3 inflammasome components. Furthermore, DHM could promote clearance of Aβ, a trigger for NLRP3 inflammasome activation, by increasing levels of NEP and shift microglial conversion to the M2‐specific agrinase‐1‐positive cell phenotype, which enhances microglial clearance of Aβ and its aggregates but not production of Aβ.ConclusionTaken together, our findings suggest that DHM prevents progression of AD‐like pathology through inhibition of NLRP3 inflammasome‐based microglia‐mediated neuroinflammation and may be a promising therapeutic drug for treating AD.

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Neuroinflammatory processes in cognitive disorders: Is there a role for flavonoids and n-3 polyunsaturated fatty acids in counteracting their detrimental effects?

Cited by 48 publications

References 173 publications

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Agathisflavone, a flavonoid derived from Poincianella pyramidalis (Tul.), enhances neuronal population and protects against glutamate excitotoxicity

Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice

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