Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

Maher, Pamela; Akaishi, Tatsuhiro; Abe, Kazuho

doi:10.1073/pnas.0607822103

Cited by 281 publications

(214 citation statements)

References 37 publications

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“…Furthermore, following a single intraperitoneal injection, fisetin was detected in the brains of rats and this correlated with a significant reduction in cerebral damage in a stroke model [73]. Similarly, we have seen significant protection in a rabbit stroke model following intravenous injection of fisetin [58] and we found that oral administration of fisetin could enhance learning and memory in mice [57]. Thus, fisetin is able to affect neuronal function in vivo.…”

Section: Metabolism Of Fisetinsupporting

confidence: 65%

“…Rolipram also had no effect on basal synaptic responses in rat hippocampal slices but facilitated LTP induced by a weak tetanic stimulus in a manner very similar to fisetin [4]. However, in contrast to rolipram, fisetin did not increase cAMP levels in the hippocampal slices [57].…”

Section: Fisetin Can Enhance Cognitive Functionmentioning

confidence: 82%

“…Cell lysates were prepared and total ATP levels were measured using a chemiluminescent assay. Adapted from [58] demonstrated that 1 lM fisetin could induce the rapid phosphorylation of CREB and that this phosphorylation was dependent on ERK activation since inhibitors of ERK activation also blocked CREB phosphorylation [57].…”

Section: Fisetin Can Enhance Cognitive Functionmentioning

confidence: 99%

“…Furthermore, age-related changes in cognitive function have been shown to correlate with impaired induction and maintenance of LTP [94]. Although fisetin had no effect on basal synaptic responses in the CA1 area of rat hippocampal slices [57], it induced LTP in slices exposed to a weak tetanic stimulus (15 pulses at 100 Hz) that by itself failed to induce LTP. The facilitation of LTP by fisetin was dose dependent, with a maximal effect seen at 1 lM and it persisted for at least 60 min.…”

Section: Fisetin Can Enhance Cognitive Functionmentioning

confidence: 99%

“…The better the mice remember the familiar object, the more time they will spend exploring the novel object. To test the effects of fisetin in this memory task, it was administered orally to the mice before the start of the training period [57]. Rolipram, administered by injection, was used as a positive control.…”

Section: Fisetin Can Enhance Cognitive Functionmentioning

confidence: 99%

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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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Section: Metabolism Of Fisetinsupporting

confidence: 65%

Section: Fisetin Can Enhance Cognitive Functionmentioning

confidence: 82%

Section: Fisetin Can Enhance Cognitive Functionmentioning

confidence: 99%

Section: Fisetin Can Enhance Cognitive Functionmentioning

confidence: 99%

Section: Fisetin Can Enhance Cognitive Functionmentioning

confidence: 99%

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

Maher

2009

Genes Nutr

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Neurotrophe Naturstoffe – ihre Chemie und Biologie

Lacoske

Theodorakis

2013

Angewandte Chemie

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Neurodegenerative Erkrankungen und Rückenmarksverletzungen betreffen weltweit etwa 50 Millionen Menschen und verursachen Gesundheitskosten von insgesamt mehr als 600 Milliarden Dollar pro Jahr. Nervenwachstumsfaktoren, d. h. Neurotrophine, sind potenzielle Therapeutika für diese Erkrankungen, denn sie können die Regeneration von Nerven fördern. Durchschnittlich 500 Publikationen jährlich belegen die Bedeutung der Neurotrophine in den biomedizinischen Wissenschaften und ihr Potenzial für therapeutische Anwendungen. Allerdings ist die klinische Verwendung von Neurotrophinen wegen ihres schlechten pharmakokinetischen Profils stark eingeschränkt. Niedermolekulare Verbindungen, die die neurotrophe Aktivität modulieren, bieten hingegen einen vielversprechenden Therapieansatz bei neurologischen Erkrankungen. Die Natur hat für eine beeindruckende Zahl von Naturstoffen mit starken neurotrophen Wirkungen gesorgt. Die aktuellen Strategien zur Synthese dieser Verbindungen sowie deren Fähigkeit, das Wachstum und die Erneuerung von Nervenzellen zu induzieren, bilden den Schwerpunkt dieses Aufsatzes. Es ist davon auszugehen, dass neurotrophe Naturstoffe nicht nur als Leitstrukturen in der Wirkstoffentwicklung genutzt werden können, sondern auch für das nächste große Projekt der Biomedizin: die Kartierung der Hirnaktivität (BAM, Brain Activity Map).

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Neurotrophic Natural Products: Chemistry and Biology

2013

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Neurodegenerative diseases and spinal cord injury affect approximately 50 million people worldwide, bringing the total healthcare cost to over 600 billion dollars per year. Nervous system growth factors, that is, neurotrophins, are a potential solution to these disorders, since they could promote nerve regeneration. An average of 500 publications per year attests to the significance of neurotrophins in biomedical sciences and underlines their potential for therapeutic applications. Nonetheless, the poor pharmacokinetic profile of neurotrophins severely restricts their clinical use. On the other hand, small molecules that modulate neurotrophic activity offer a promising therapeutic approach against neurological disorders. Nature has provided an impressive array of natural products that have potent neurotrophic activities. This Review highlights the current synthetic strategies toward these compounds and summarizes their ability to induce neuronal growth and rehabilitation. It is anticipated that neurotrophic natural products could be used not only as starting points in drug design but also as tools to study the next frontier in biomedical sciences: the brain activity map project.

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Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

Cited by 281 publications

References 37 publications

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

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

Neurotrophe Naturstoffe – ihre Chemie und Biologie

Neurotrophic Natural Products: Chemistry and Biology

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