A comparison of the neurotrophic activities of the flavonoid fisetin and some of its derivatives

Neurotrophic factors promote the development, maintenance and regeneration of nerve cells. Classical neurotrophic factors are proteins and thus not well-suited for therapeutic purposes. Recently, we showed that specific flavonoids such as fisetin (3, 7, 3', 4' tetrahydroxyflavone) promote the differentiation of nerve cells in culture through the activation of extracellular signal-regulated kinase (ERK) suggesting that flavonoids could substitute for neurotrophic factors. It has also been shown that fisetin promotes nerve cell survival following exposure to toxic oxidative insults. To determine whether or not this is unique to fisetin, a series of related compounds were assayed for neurotrophic activities. Many of these related compounds also promote nerve cell differentiation and are neuroprotective against toxic oxidative insults. However, the mechanisms underlying these neurotrophic effects differ among the compounds.