The neurotrophic activities of brain-derived neurotrophic factor are potentiated by binding with apigenin, a common flavone in vegetables, in stimulating the receptor signaling

AimsWe aimed to identify the neurotrophic activities of apigenin (4 ',5,7-trihydroxyflavone) via its coordination with brain-derived neurotrophic factor (BNDF) and an elevated signaling of tyrosine kinase receptor B (Trk B receptor). MethodsThe direct binding of apigenin to BDNF was validated by ultrafiltration and biacore assay. Neurogenesis, triggered by apigenin and/or BDNF, was determined in cultured SH-SY5Y cells and rat cortical neurons. The amyloid-beta (A beta)(25-35)-induced cellular stress was revealed by propidium iodide staining, mitochondrial membrane potential, bioenergetic analysis, and formation of reactive oxygen species levels. Activation of Trk B signaling was tested by western blotting. ResultsApigenin and BDNF synergistically maintained the cell viability and promoted neurite outgrowth of cultured neurons. In addition, the BDNF-induced neurogenesis of cultured neurons was markedly potentiated by applied apigenin, including the induced expressions of neurofilaments, PSD-95 and synaptotagmin. Moreover, the synergy of apigenin and BDNF alleviated the (A beta)(25-35)-induced cytotoxicity and mitochondrial dysfunction. The synergy could be accounted by phosphorylation of Trk B receptor, and which was fully blocked by a Trk inhibitor K252a. ConclusionApigenin potentiates the neurotrophic activities of BDNF through direct binding, which may serve as a possible treatment for its curative efficiency in neurodegenerative diseases and depression.

Automated summary

We aimed to investigate the neurotrophic activities of apigenin (4',5,7-trihydroxyflavone) through its interaction with brain-derived neurotrophic factor (BDNF) and the activation of tyrosine kinase receptor B (Trk B receptor). Our results showed that apigenin and BDNF synergistically enhanced the survival and neurite outgrowth of cultured neurons. Apigenin also potentiated the neurogenesis induced by BDNF and protected against amyloid-beta-induced cytotoxicity and mitochondrial dysfunction. These effects were mediated by the phosphorylation of Trk B receptor. In conclusion, apigenin can enhance the neurotrophic effects of BDNF and may have therapeutic potential in neurodegenerative diseases and depression.