Neurological effects of honey: current and future prospects

Abstract

Honey is the only insect-derived natural product with therapeutic, traditional, spiritual, nutritional, cosmetic, and industrial value. In addition to having excellent nutritional value, honey is a good source of physiologically active natural compounds, such as polyphenols. Unfortunately, there are very few current research projects investigating the nootropic and neuropharmacological effects of honey, and these are still in their early stages. Raw honey possesses nootropic effects, such as memory-enhancing effects, as well as neuropharmacological activities, such as anxiolytic, antinociceptive, anticonvulsant, and antidepressant activities. Research suggests that the polyphenol constituents of honey can quench biological reactive oxygen species and counter oxidative stress while restoring the cellular antioxidant defense system. Honey polyphenols are also directly involved in apoptotic activities while attenuating microglia-induced neuroinflammation. Honey polyphenols are useful in improving memory deficits and can act at the molecular level. Therefore, the ultimate biochemical impact of honey on specific neurodegenerative diseases, apoptosis, necrosis, neuroinflammation, synaptic plasticity, and behavior-modulating neural circuitry should be evaluated with appropriate mechanistic approaches using biochemical and molecular tools.

Figure 1

The putative neuroprotective mechanism of honey and its polyphenols. The generation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) increases irrespective of neurodamaging insults that lead to oxidative stress. The dysfunction of the antioxidant defense system synergistically causes reactive species accumulation, leading to oxidative stress. The ultimate outcome of such oxidative stress is neuronal cell death through an inflammatory, apoptotic, or necrotic response [–114, 116, 119]. Honey (H) and its polyphenol constituents (HP) can counter oxidative stress by limiting the generation of reactive species as well as by strengthening the cellular antioxidant defense system. Honey and several honey polyphenols (apigenin, ferulic acid, and catechin) prevent neuronal cell death by attenuating neuroinflammation and apoptosis. However, the neuroinflammatory responses overlap with apoptosis, and the role of honey in necrotic cell death remains unclear. X = stop or prevent and + = improve or intensify.

Figure 2

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 [–128]. Honey polyphenols (HP: luteolin, myricetin, catechin) modulate synaptic plasticity through the activation of CREB by MAPK/ERKs and/or PKA-involved cellular signaling.