Evaluation of the anti-allergic activity of Citrus unshiu using rat basophilic leukemia RBL-2H3 cells as well as basophils of patients with seasonal allergic rhinitis to pollen

The anti-allergic activity of the 50% methanol extract of Citrus unshiu powder (MEC) was examined. Fifty percent methanol extract of MEC powder showed potent inhibitory activity against histamine release from basophils of patients suffering from seasonal allergic rhinitis to ceder pollen. To examine this anti-allergic mechanism in detail, we next used rat basophlilic leukemia RBL-2H3 cells. MEC significantly inhibited IgE-induced histamine and β-hexosaminidase release from RBL-2H3 cells. Since MEC contains a variety of flavonoids, we selected nobiletin, hesperetin, and hesperidin (hesperetin glycoside) as representative compounds, and further evaluated these inhibitory activities. Among the flavonoids tested, hesperetin was the most potent, while hesperidin had far less, if any, inhibitory activity. The mechanism by which flavonoids inhibited the degranulation process was then examined. As a result, hesperetin and nobiletin suppressed the phosphorylation of Akt-1, direct downstream effector of phosphatidylinositol 3-kinase (PI3-K). Thus, it was assumed that these flavonoids suppressed IgE-mediated stimulation of basophils through PI3-K pathway and that proper intake of Citrus unshiu would be favorable for managing seasonal allergic rhinitis to ceder pollen.