Structural requirements of flavonoids for inhibition of antigen-Induced degranulation, TNF-α and IL-4 production from RBL-2H3 cells Original Research Article

To clarify the structure–activity relationships of flavonoids for antiallergic activity, the inhibitory effects of various flavonoids on the release of β-hexosaminidase, as a marker of degranulation of RBL-2H3 cells, were examined. Among them, luteolin (IC50=3.0 μM), diosmetin (2.1 μM), and fisetin (3.0 μM) were found to show potent inhibitory activity, and the results suggested the following structural requirements of flavonoids: (1) the 2-3 double bond of flavones and flavonols is essential for the activity; (2) the 3- or 7-glycoside moiety reduced the activity; (3) as the hydroxyl groups at the 3′-, 4′-, 5-, 6-, and 7-positions increased in number, the inhibitory activities become stronger; (4) the flavonols with a pyrogallol type moiety (the 3′,4′,5′-trihydroxyl groups) at the B ring exhibited less activity than those with a phenol type moiety (the 4′-hydroxyl group) or catechol type moiety (the 3′,4′-dihydroxyl groups) at the B ring; (5) the activities of flavones were stronger than those of flavonols; and (6) methylation of flavonols at the 3-position reduced the activity. However, (7) several flavones and flavonols with the 4′- and/or 7-methoxyl groups did not obey rules (3), (4), and (5). In addition, several flavonoids, that is apigenin, luteolin, diosmetin, fisetin, and quercetin, inhibited the antigen-IgE-mediated TNF-α and IL-4 production from RBL-2H3 cells, both of which participate in the late phase of type I allergic reactions.