Effect of Citrus polymethoxyfavones on neuritogenesis in neuroblastoma cells

We previously reported that 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), one of the Citrus polymethoxyflavones (PMFs), has the ability to activate extracellular signal-regulated kinases 1/2 (ERK1/2) in cultured neurons, as well as that to rescue mice from drug-induced learning impairment. The present study showed that 1) HMF activated ERK1/2 in Neuro2a cells, a mouse neuroblastoma cell line used as a model system for studies on neuronal differentiation; 2) HMF promoted neurite outgrowth from Neuro2a cells; and 3) nobiletin (5,6,7,8,3′,4′-hexamethoxy flavone, NBT), another PMF, acted similarly as HMF. Our findings lend further support to the notion that PMFs might be neurotrophic agents useful for the treatment of various neurodegenerative neurological disorders.