Neurological Effects of Honey: Current and Future Prospects
Putative nootropic mechanisms of honey and its polyphenols. Calcium influx via the N-methyl-D-aspartate receptor (NMDAR) occurs during the initial phase of NMDAR-dependent LTP. The inductive phase follows CREB phosphorylation through MAPK/ERKs signaling, which ultimately leads to the transcriptional regulation of synaptic plasticity-related proteins. Metabotropic receptors include ligand-gated ion channels that promote calcium influx (AMPA receptor) and enzyme-coupled receptors (such as cholinergic, glutamate, and dopamine receptors) that can trigger a second messenger (cAMP/cGMP) to activate downstream effector enzymes. The effector enzymes finally modulate the activation of CREB [123–128]. Honey polyphenols (HP: luteolin, myricetin, catechin) modulate synaptic plasticity through the activation of CREB by MAPK/ERKs and/or PKA-involved cellular signaling.