Search Results (2)

Allergic rhinitis (AR) affects 20–50% of the global population. Available treatments are limited by their adverse effects. We investigated the anti-allergic effects of catechin alone and combined with cetirizine against ovalbumin-induced AR. Rats were sensitized with ovalbumin and received catechin (14 days) and then challenged with aerosolized ovalbumin (1%) to determine AR clinical scores. Histamine, histamine release, and histidine decarboxylase (HDC) activity were determined in blood, peritoneal mast cells, and stomachs, respectively. Vascular permeability and safety were assessed using Evans blue leakage and barbiturate-induced sleeping-time assays, respectively. Catechin and cetirizine binding with HDC was investigated by docking and binding energy analyses. The clinical scores of the combination regimen were superior to either drug alone. All treatments reduced vascular leakage, with no effect on barbiturate-induced sleeping time. Only the catechin-treated rats showed reduced histamine levels and HDC activity. Docking studies revealed that catechin has a 1.34-fold higher extra-precision docking score than L-histidine. The binding energy scores for catechin-HDC, L-histidine-HDC, and histamine-HDC were −50.86, −37.64, and −32.27 kcal/mol, respectively. The binding pattern of catechin was comparable to the standard HDC inhibitor, histidine methyl ester, but with higher binding free energy. Catechin binds the catalytic residue S354, unlike cetirizine. The anti-allergic effects of catechin can be explained by HDC inhibition and possible antihistaminic activity. Full article

The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we demonstrate that disruption or potentiation of histaminergic neurotransmission differentially affects short (STM) and long-term (LTM) social recognition memory. Impairments of LTM, but not STM, were observed in histamine-deprived animals, either chronically (Hdc^−/− mice lacking the histamine-synthesizing enzyme histidine decarboxylase) or acutely (mice treated with the HDC irreversible inhibitor α-fluoromethylhistidine). On the contrary, restriction of histamine release induced by stimulation of the H₃R agonist (VUF16839) impaired both STM and LTM. H₃R agonism-induced amnesic effect was prevented by pre-treatment with donepezil, an acetylcholinesterase inhibitor. The blockade of the H₃R with ciproxifan, which in turn augmented histamine release, resulted in a procognitive effect. In keeping with this hypothesis, the procognitive effect of ciproxifan was absent in both Hdc^−/− and αFMH-treated mice. Our results suggest that brain histamine is essential for the consolidation of LTM but not STM in the social recognition test. STM impairments observed after H₃R stimulation are probably related to their function as heteroreceptors on cholinergic neurons. Full article