Plant-Derived Diamine Oxidase Modulation of Histamine-Induced Ca2+ Release in Intestinal Caco-2 Cells: A Cellular System to Evaluate Its Histaminase Efficacy

Histamine accumulation is associated with allergic reactions and intestinal dysfunction through activation of H1R Receptors (H1Rs) and subsequent intracellular Ca2+ mobilization. Although antihistamines such as desloratadine block H1Rs to alleviate symptoms, they may induce adverse effects (dizziness, nausea, neurological disorders). Diamine oxidases (DAOs) catalyze the oxidative deamination of histamine to imidazole acetaldehyde with consumption of oxygen and concomitant production of hydrogen peroxide and ammonia. Instead of blocking H1R, we have proposed vegetal diamine oxidase (vDAO) as an enzymatic approach to decompose histamine. This study investigated whether vDAO, by degrading histamine, could modulate histamine-induced Ca2+ mobilization compared with desloratadine. Using intestinal Caco-2 cultured cells loaded with the fluorescent Ca2+ indicator Fluo-4 AM, intracellular calcium (Ca2+) dynamics were analyzed by confocal microscopy following histamine stimulation. vDAO significantly downregulated histamine-induced Ca2+ mobilization. Notably, at a fixed histamine concentration sufficient to trigger Ca2+ release, vDAO achieved the same level of calcium mobility inhibition at a concentration three-fold lower than that of desloratadine, suggesting a high efficiency of DAO. These findings indicate that histamine degradation with orally administrable DAO may reduce Ca2+ signaling in intestinal epithelial cells, providing a promising approach to reduce histamine-related damage or a reinforcement of current antihistamine anti-inflammatory medication based on histamine receptor blockade.