Neuritogenic effect of sea cucumber glucocerebrosides on NGF-induced PC12 cells via activation of the TrkA/CREB/BDNF signalling pathway

Sea cucumber glucocerebrosides (SCGs), an important sphingolipid, have extensive functions in inhibiting the growth of cancer cells, but their potential to promote neuronal outgrowth hasn't been well studied. Herein, we evaluated the neuritogenic effects of three Cucumaria frondosa SCGs series (SCG-1, SCG-2, and SCG-3) in NGF-induced PC12 cells. These SCGs exhibited significant neuritogenic effects in a dose-dependent and structure-selective manner, which increased the ratio of neurite-bearing cells and expression of axonal (GAP-43) and synaptic (synaptophysin) proteins. Mechanistic studies suggested that SCGs reinforced the NGF-induced phosphorylation of TrkA, coupled with ERK1/2 activation, then triggered the activation of CREB, finally resulted in a marked increase of BDNF expression. Furthermore, the neuritogenic effects of SCGs could be suppressed when accompanied by the additions of TrkA inhibitor GW441765 or MEK inhibitor U0126. In conclusion, SCGs possess a marked neuritogenic effect that promotes the signalling downstream from TrkA, likely via the MEK/ERK1/2/CREB/BDNF pathway.