Study on the Effect and Mechanism of Lupatadine Fumarate in the Treatment of Allergic Rhinitis

Summary

In China, the prevalence of allergic rhinitis reaches 17.6% and is increasing year by year, seriously affecting the quality of life of patients. Some patients still cannot be effectively treated. So it is urgent to study the pathogenesis of AR and find new therapeutic targets. Lupatadine fumarate has the dual effects of antihistamine and platelet-activating factor (PAF), and it is the only potent and highly effective allergy drug with both antihistamine and PAF antagonism currently on the marke. The exact mechanism of Lupatadine fumarate in relieving nasal congestion in patients with AR is unknown. Tight junction proteins (TJs) play an important role in maintaining endothelial barrier function, and TJ disruption disrupts barrier function and promotes inflammation. 15-LOX(15-lipoxygenase) disrupts tight junctions at the blood-brain barrier. It increases cerebral vascular permeability and contributes to cerebral edema. In a mouse model of atherosclerosis, 15(S)-HETE, the major metabolite of 15-LOX, enhances the phosphorylation of ZO-2 at the Thr-1/1 residue through MEK1-ERK770/772 activation, leading to the dissociation of ZO-1 from occludin and disrupting the endothelial TJ and its barrier function. So we want to study the effects and mechanisms of lupatadine fumarate in the treatment of allergic rhinitis (AR) and whether lupatadine fumarate is directly related to 15-LO1.

Timeline

Start

2024-03-01

Primary completion

2024-12

Completion

2026-12

Publications

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• Background Cong X, Kong W. Endothelial tight junctions and their regulatory signaling pathways in vascular homeostasis and disease. Cell Signal. 2020 Feb;66:109485. doi: 10.1016/j.cellsig.2019.109485. Epub 2019 Nov 23.

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