Effect of concurrent administration of nobiletin and β-lactoglobulin on the symptoms of Japanese cedar pollinosis models in mice

Nobiletin and β-lactoglobulin were previously demonstrated to suppress mast cell de-granulation in vitro and in vivo. In this study, the multiple anti-allergic effects of both substances by simultaneous treatment were examined in order to determine if they could further mitigate allergic symptoms. Concurrent treatment with nobiletin and β-lactoglobulin effectively suppressed de-granulation of RBL-2H3 cells by inhibiting increases in intracellular Ca2+ concentration. Immunoblot analysis showed that phosphorylation of phosphoinositide 3-kinase, Akt, and Syk in RBL-2H3 cells was all inhibited by the concurrent presence of nobiletin and β-lactoglobulin. Moreover, concurrent administration of nobiletin and β-lactoglobulin reduced passive cutaneous anaphylaxis (PCA) reaction in mice compared with nobiletin or β-lactoglobulin administered alone. In addition, the concurrent administration of freeze-dried Citrus unshiu peel powder and yogurt whey containing these bioactive substances also reduced PCA reaction and allergic symptoms of a murine model of Japanese cedar pollinosis.