Study on the effect and mechanism of sesamin on P2X3-related cheek allergic contact dermatitis in mice induced by SADBE stimulation.

Allergic contact dermatitis (ACD) is a common inflammatory skin condition characterized by cutaneous inflammation and pruritus. Purinergic 2X receptor 3 (P2X3) and transient receptor potential ankyrin 1 (TRPA1) are implicated in acute and chronic pruritus, but their interactions remain unclear. Sesamin has anti-inflammatory, antioxidant, and antitumor properties; however, its effectiveness in alleviating ACD and the underlying mechanism remain unknown. In this study, male C57BL/6 mice (20-25 g body weight) were used. Results showed that squaric acid dibutylester (SADBE) increased scratching behavior and upregulated P2X3, TRPA1, IL-1β, and TNF-α expression in the right trigeminal ganglion (TG). Intraperitoneal administration of sesamin attenuated these effects, reducing pruritic behavior and inflammation-related gene expression. Compared to the control group, the ACD model group showed significantly increased co-expression of Mas-related G protein-coupled receptor member A3 (MrgprA3) and P2X3. Transfection experiments in HEK293 cells demonstrated that P2X3 regulated TRPA1 channel activation by modulating intracellular calcium levels. These findings suggest that sesamin alleviates pruritus in ACD mice, likely through downregulation of P2X3 and suppression of P2X3-mediated intracellular calcium elevation. Furthermore, sesamin inhibited TRPA1 expression and reduced calcium levels in cells co-transfected with the TRPA1 plasmid. Thus, sesamin may attenuate activation and expression of the inflammatory receptor TRPA1 by inhibiting P2X3, highlighting its potential as an antipruritic agent for SADBE-induced ACD.