Potential of N-trans feruloyl tyramine from Lycium barbarum fruit extract on neurogenesis and neurotrophins; targeting TrkA/ERK/CREB signaling pathway

[Display omitted] •Lycium barbarum fruit extract (LB-E) exerted neurotrophic effects by regulating TrkA/ERK/CREB signaling.•N-trans feruloyl tyramine (NTFT) as an active component of LB-E might be engaged to enhance the neurite growth-related neurotrophins.•NTFT from LB-E may be potential therapeutic agents for age-related brain diseases caused by the deficiency of neurotrophins. This study was aimed to evaluate the potential neurotrophic effect of Lycium barbarum fruit extract (LB-E) via increased neurite outgrowth and synaptic formation, and its neurotrophic and neuroprotective efficacy was also checked in vitro. LB-E exerted neurotrophic effects by regulating TrkA/ERK/CREB signaling. In nervous system, LB-E promoted neuronal survival and differentiation by increasing neurotrophic factor secretion in C6 glioma cells. Interestingly, LB-E increased the expressed levels of synaptophysin and GAP-43 in CNS cell lines. It also subsequently increased the number of ciliated cells and length of cilia in N1 hypothalamic neuronal cells induced by CNTF and displayed the enhanced dendrite length in primary cortical neurons. We investigated N-trans feruloyl tyramine (NTFT) from LB-E by LC-MS/MS, and confirmed NTFT as a biologically active ingredient showing the neurotrophic effect. These results suggested that NTFT from LB-E may be beneficial in the treatment of age-related brain diseases caused by the deficiency of neurotrophins.