title: Inhibitory effects of thunberginols A, B, and F on degranulations and releases of TNF-alpha and IL-4 in RBL-2H3 cells.
abstract: Thunberginols A, B, and F from the processed leaves of Hydrangea macrophylla var. thunbergii (Hydrangeae Dulcis Folium) substantially inhibited the degranulations by antigen and calcium ionophore A23187, and the releases of TNF-alpha and IL-4 by antigen in RBL-2H3 cells. Phyllodulcin and hydrangenol also showed significant inhibition for the antigen-induced degranulations, but their effects were weaker than those of thunberginols A, B, and F. Among them, thunberginol B showed the most potent activity. With regard to structural requirements of thunberginols for the activity, the 3,4-double bond was essential for the strong activity and the 6-hydroxyl group and lactone ring enhanced the activity. Thunberginols A, B, and F inhibited increase in intracellular free Ca2+ levels, which is an essential process for the degranulation and production of cytokines, in RBL-2H3 cells induced by antigen, but not by calcium ionophore A23187. These results suggested that these active compounds inhibited the degranulation processes both before and after increase in intracellular free Ca2+ levels.
authors.affiliation: Kyoto Pharmaceutical University, Japan.
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Koudai
authors.initials: K
authors.lastname: Matsuhira
authors.forename: Seikou
authors.initials: S
authors.lastname: Nakamura
authors.forename: Dan
authors.initials: D
authors.lastname: Yuan
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D004140:Dinitrophenols / Q000276:immunology; D031966:Hydrangea / Q000737:chemistry; D015847:Interleukin-4 / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D049934:Isocoumarins / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D012710:Serum Albumin, Bovine / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000941:Antigens; D004140:Dinitrophenols; D007476:Ionophores; D049934:Isocoumarins; D014409:Tumor Necrosis Factor-alpha; C034638:dinitrophenyl-bovine serum albumin; C079055:thunberginol A; C079056:thunberginol B; C079057:thunberginol F; D015847:Interleukin-4; D012710:Serum Albumin, Bovine; D000001:Calcimycin; D001619:beta-N-Acetylhexosaminidases; D002118:Calcium