Neurotrophic activity of obovatol on the cultured embryonic rat neuronal cells by increase of neurotrophin release through activation of ERK pathway

Previously we found that obovatol a lignan compound Isolated from Magnolia officinalis has anti-cancer anti-inflammatory and anxiolytic effects Recent studies showed that honokiol magnolol and 4 O-methylhonokiol lignin compounds isolated from the Magnolia family have neurotrophic activity In this study we examined whether or not obovatol also exhibits neurite-promoting effects on rat embryonic neuronal cells Obovatol Increased neurite outgrowth in a concentration dependent manner Consistent with the neurite outgrowth effect the expression of neurite differentiation markers also increased in response to obovatol We also found that obovatol increased levels of NGF and BDNF released into the culture medium In addition the combination of low concentrations of obovatol (1 and 2 mu M) with NGF (50 ng/ml) or with BDNF (10 ng/ml) greatly enhanced neurite outgrowth Subsequently we found that obovatol increased phosphorylation of ERK However the neurite outgrowth and NGF and BDNF release induced by obovatol were prevented by an ERK-specific inhibitor These results suggest that obovatol promotes neurite outgrowth due to the increased release of neurotrophic factors via activation of the ERK pathway Crown Copyright (C) 2010 Published by Elsevier B V All rights reserved