Extension of dendrites and axons in neurons may compensate and rescue damag
ed neuronal networks in the dementia brain. Our aim is to isolate and ident
ify constituents of coffee beans exhibiting neurite outgrowth activity. Amo
ng the extracts of raw and roasted coffee beans, a methanol fraction of the
ethanol extract (1 mu g/ml) of raw beans increased significantly the perce
ntage of cells with neurites in human neuroblastoma SK-N-SH cells. Among su
bfractions of this methanol fraction was a basic fraction (5 mu g/ml) which
exhibited significant neurite outgrowth activity. Finally, trigonelline in
the basic fraction was identified to be active as far neurite extension wa
s concerned. Treatment with trigonelline (30 mu M) increased the percentage
of cells with neurites at 3 and 6 d after treatment. In addition, the numb
er of neurites reacting positively to phosphorylated neurofilament-H was in
creased by treatment with 30 mu M trigonelline for 6 d, suggesting enhancem
ent of axonal extension. These results show that trigonelline promotes func
tional neurite outgrowth.