Suppressive effects of flavonoid fisetin on lipopolysaccharide-induced microglial activation and neurotoxicity

Zheng, Long Tai; Ock, Jiyeon; Kwon, Byoung‐Mog; Suk, Kyoungho

doi:10.1016/j.intimp.2007.12.012

Cited by 152 publications

(108 citation statements)

References 51 publications

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“…25,47,48 Neuron and axon density are critical indicators of anatomical recovery from SCI. 43,49 In histopathologic examination, a statistically significant increase of NF was observed in the ZNS-M group (Figure 9). Injury to neurons stimulates a rapid production of superoxide, resulting in cell death.…”

Section: Zns-m Groupsmentioning

confidence: 91%

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Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system for the treatment of acute spinal cord injury

Li¹,

Deng²,

Yuan³

et al. 2017

IJN

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Section: Zns-m Groupsmentioning

confidence: 91%

“…The activated microglial cells can induce oxidative stress when cultured with neuronal cells. 42,43 Although the response is natural, oxidative stress can be detrimental to …”

mentioning

confidence: 99%

Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system for the treatment of acute spinal cord injury

Li¹,

Deng²,

Yuan³

et al. 2017

IJN

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“…Flavonoids may exert these effects via direct modulation of protein and lipid kinase signalling pathways [98,105,130], for example via the inhibition of MAPK signalling cascades, such as p38 or ERK1/2 which regulate both iNOS and TNF-a expression in activated glial cells [9]. In this respect, fisetin inhibits p38 MAP kinase phosphorylation in LPS-stimulated BV-2 microglial cells [136] and the flavone luteolin inhibits IL-6 production in activated microglia via inhibition of the JNK signalling pathway. The effects of flavonoids on these kinases may influence downstream pro-inflammatory transcription factors important in iNOS transcription.…”

Section: Inhibition Of Neuroinflammationmentioning

confidence: 99%

The neuroprotective potential of flavonoids: a multiplicity of effects

et al. 2008

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Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.

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“…A recent paper demonstrated that fisetin could reduce bacterial lipopolysaccharide (LPS)-induced microglial activation and neurotoxicity [96]. Using the BV-2 microglial cell line, it was shown that fisetin was very effective at blocking LPS-induced nitric oxide production, measured as accumulation of nitrite in the culture medium, with an EC 50 of *7 lM.…”

Section: Anti-inflammatory Effects Of Fisetinmentioning

confidence: 99%

Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin

Maher

2009

Genes Nutr

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Multiple factors have been implicated in the age-related declines in brain function. Thus, it is unlikely that modulating only a single factor will be effective at slowing this decline. A better approach is to identify small molecules that have multiple biological activities relevant to the maintenance of brain function. Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also maintain mitochondrial function in the presence of oxidative stress. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of 5-lipoxygenase, thereby reducing the production of lipid peroxides and their pro-inflammatory by-products. This wide range of actions suggests that fisetin has the ability to reduce the age-related decline in brain function.

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Suppressive effects of flavonoid fisetin on lipopolysaccharide-induced microglial activation and neurotoxicity

Cited by 152 publications

References 51 publications

Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system for the treatment of acute spinal cord injury

Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system for the treatment of acute spinal cord injury

The neuroprotective potential of flavonoids: a multiplicity of effects

Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin

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