title: Phenolic substances from Phagnalon rupestre protect against 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity.
abstract: 2-isoprenylhydroquinone-1-glucoside (1), 3,5-dicaffeoylquinic acid (2), and 3,5-dicaffeoylquinic acid methyl ester (3), isolated from Phagnalon rupestre, improved the contact hypersensitivity response to 2,4,6-trinitrochlorobenzene in mice. These phenolics reduced ear swelling and IL-1β content by 50% 24 h after challenge; in addition, 2 inhibited tumor necrosis factor-α by 53%. All three compounds also reduced interleukin-2 content by 50% 72 h after challenge. Both 2 and 3 inhibited metalloproteinase-9 levels in the skin lesions by 66% and 41%, respectively, and lowered cyclooxygenase-2 expression by 44% and 49%, respectively, at 24 h. Moreover, 2 was effective against atopic dermatitis induced by repeated application of 2,4,6-trinitrochlorobenzene; it attenuated edema by over 40% from day 7 and inhibited inflammatory cell infiltration by 44% at day 22. In addition, 1-3 reduced metalloproteinase-9 expression in a dose-dependent manner in macrophages RAW 264.7 stimulated with lipopolysaccharide. Thus, compounds 2 and 3 were found to exhibit a greater activity against contact hypersensitivity than 1.
authors.affiliation: Departament de Farmacologia, Facultat de Farmàcia, Universitat de València , Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giner
authors.forename: Mariya
authors.initials: M
authors.lastname: El Alami
authors.forename: Salvador
authors.initials: S
authors.lastname: Máñez
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Recio
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Ríos
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Giner
mesh_terms: D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced; D053583:Interleukin-1beta / Q000032:analysis / Q000378:metabolism; D007376:Interleukin-2 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010853:Picryl Chloride / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D053583:Interleukin-1beta; D007376:Interleukin-2; D008070:Lipopolysaccharides; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; D010853:Picryl Chloride