Methods of Using Flavonoids to Enhance Memory
Inventors: Pamela Maher
Potential Uses: Drug Discovery and Development, Neutraceuticals.
A plant derived small molecule, the flavonoid Fisetin, shows efficacy as a neurotrophic factor promoting the differentiation of nerve cells, and has been shown to enhance long-term memory in mice. Polyphenolic compounds such as these may prove more effective than classical neurotrophic factors in treating neurological disorders.
Neurotrophic factors promote the differentiation, survival, and functional maintenance of nerve cells. Because of these properties, they have the potential to treat a variety of chronic and acute disorders of the central nervous system. Although there have been some successes, clinical use of classical neurotrophic factors, such as brain-derived neurotrophic factor, has been limited for technical reasons, including difficulty in crossing the blood-brain barrier. Therefore, the identification of small molecules that mimic some or all of the properties of neurotrophic factors could have significant potential for treating CNS disorders.
A previous study by the inventor described the ability of the flavonoid Fisetin to promote the differentiation of nerve cells. Although a wide range of flavonoids were tested in that study, most failed to induce differentiation. Of the few effective flavonoids, Fisetin showed significantly greater efficacy than any of the others. The induction of differentiation by Fisetin depends on the activation of the Ras-extracellular signal-regulated kinase (ERK) cascade and in particular on the activation of the ultimate kinase in this cascade, ERK. Inhibitors of both Ras and ERK activation block Fisetin induced differentiation.
Not only does Fisetin promote nerve cell differentiation, but in earlier studies it was shown to protect nerve cells from oxidative stress-induced death. Thus, Fisetin has several of the properties of classical neurotrophic factors. Experimental measurement shows that Fisetin facilitates LTP (Long Term Potentiation), the long-lasting strengthening of the connection between two nerve cells that is considered to be the cellular basis of learning and memory. Further experimentation with mice given Fisetin orally before training in an Object Discrimination Protocol indicates that Fisetin enhances long-term memory in mice.
Fisetin could be useful for promoting memory in both normal subjects and in patients with neurological disorders, and its additional neurotrophic activities make Fisetin particularly attractive for promoting overall healthy brain function.
Patent Status: U.S. Patent Application published as US-2008/0021096 A1
Publications: PNAS 103(44):16568-73 (31 October 2006)
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