Reduction of neurite extension by piperine, examined on hippocampal and septal neurons in serum-free cultures.

The presence of piperine in a serum-free medium for 72 h markedly inhibited the neurite extension of cultured hippocampal and septal neurons under both high and low density cell culture conditions (initial cell density was 10(5) cells/cm2 and 2.5-5 x 10(3) cells/cm2, respectively). The average length of neurites decreased over a concentration range of piperine (12.5-100 microM), and the distribution of neurite population shifted towards the shorter neurite lengths whereas an increase in the soma size was observed only with high piperine concentrations (75 and 100 microM, in a high density cell culture). This indicates that the piperine effect was relatively selective to the neurite extension. The neurite extension in low density cell cultures was considerably more susceptible to piperine than that in high density cell cultures (hippocampus: EC50 = 39 versus 113 microM, septum: EC50 = 48 versus 101 microM, in the low and high density cell cultures, respectively). This difference may be due to a lack of neurotrophic supports from non-neuronal cells under the low density cell culture condition. These findings suggest that piperine, in addition to its cytotoxic effect on the neuronal survival, suppresses the neurite extension in developing neurons.