Structural requirements of flavonoids for inhibition of antigen-Induced degranulation, TNF-alpha and IL-4 production from RBL-2H3 cells.
To clarify the structure-activity relationships of flavonoids for antiallergic activity, the inhibitory effects of various flavonoids on the release of beta-hexosaminidase, as a marker of degranulation of RBL-2H3 cells, were examined. Among them, luteolin (IC(50)=3.0 microM), diosmetin (2.1 microM), and fisetin (3.0 microM) 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-alpha and IL-4 production from RBL-2H3 cells, both of which participate in the late phase of type I allergic reactions.
Mastuda
Hisashi
H
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan.
Morikawa
Toshio
T
Ueda
Kazuho
K
Managi
Hiromi
H
Yoshikawa
Masayuki
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry* / Q000494:pharmacology; D000941:Antigens / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology; D004140:Dinitrophenols / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D044948:Flavonols; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D047311:Luteolin; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D001619:beta-N-Acetylhexosaminidases / Q000187:drug effects / Q000378:metabolism
D018926:Anti-Allergic Agents; D000941:Antigens; D004140:Dinitrophenols; D005419:Flavonoids; D044948:Flavonols; D014409:Tumor Necrosis Factor-alpha; C034638:dinitrophenyl-bovine serum albumin; D015847:Interleukin-4; D012710:Serum Albumin, Bovine; D001619:beta-N-Acetylhexosaminidases; D047311:Luteolin; C017875:fisetin; C039602:diosmetin