Honey-Mediated Wound Healing: H₂O₂ Entry through AQP3 Determines Extracellular Ca Influx.

Since Biblical times, honey has been utilized in "folk medicine", and in recent decades the positive qualities of honey have been re-discovered and are gaining acceptance. Scientific literature states that honey has been successfully utilized on infections not responding to classic antiseptic and antibiotic therapy, because of its intrinsic H₂O₂ production. In our study, we demonstrated the involvement of H₂O₂ as a main mediator of honey regenerative effects on an immortalized human keratinocyte cell line. We observed that this extracellularly released H₂O₂ could pass across the plasma membrane through a specific aquaporin (i.e., AQP3). Once in the cytoplasm H₂O₂, in turn, induces the entry of extracellular Ca through Melastatin Transient Receptor Potential 2 (TRPM2) and Orai1 channels. Honey-induced extracellular Ca entry results in wound healing, which is consistent with the role played by Ca signaling in tissue regeneration. This is the first report showing that honey exposure increases intracellular Ca concentration ([Ca]), due to H₂O₂ production and redox regulation of Ca-permeable ion channels, opening up a new horizon for the utilization of the honey as a beneficial tool.