Spirodela polyrhiza and its Chemical Constituent Vitexin Exert Anti-Allergic Effect via ORAI1 Channel Inhibition

Intracellular calcium signaling cascades are integral to early and late allergic responses involving mast cell degranulation and type 2 helper T cell activation, respectively. Both the responses are accompanied by the movement of calcium through the calcium release-activated calcium (CRAC) channel, encoded by the ORAI1 gene. Spirodela polyrhiza (L.) Schleid (SP) has anti-inflammatory and anti-allergic effects, but its effect on calcium signaling has not been reported. This study investigated whether a 30% ethanolic SP extract (SPEtQH) and its constituents can reduce CRAC currents (I-C(RAC)), and thus inhibit mast cell degranulation and T cell activation. In Jurkat T lymphocytes, we found that 3 mg/mL SPEtOH inhibited the I-CR(AC) by 81.0 +/- 11.1%, whereas one of its constituents vitexin (100 mu M) inhibited the I-CR(AC) by 48.9 +/- 8.71%. Furthermore, in the RBL-2H3 mast cell, the I-CR(AC) was inhibited by 3 mg/mL SPEtOH (86.7 +/- 5.83%) and 100 mu M vitexin (47.5 +/- 5.67%). Investigation of human primary T cell proliferation induced by co-stimulation with antibodies to cluster of differentiation 3 and 28, and of RBL-2H3 mast cell degranulation following IgE-antigen complex stimulation revealed that 100 mu M vitexin inhibited both T-cell proliferation (by 34.8 +/- 6.08%) and mast cell degranulation (by 36.7 +/- 0.07%). These effects were concentration-dependent, and no cytotoxicity was observed. Our findings suggest that vitexin is a promising candidate compound for the development of therapeutic agents to prevent and treat allergic diseases.