New insight into the inhibition of the inflammatory response to experimental delayed-type hypersensitivity reactions in mice by scropolioside A.
Scropolioside A, an iridoid isolated from Scrophularia auriculata ssp. pseudoauriculata, showed anti-inflammatory properties against different experimental models of delayed-type hypersensitivity. This iridoid reduced the oedema induced by oxazolone by 79% (72 h) at 0.5 mg/ear while reducing that induced by sheep red blood cells by 47% (18 h), 45% (24 h) and 36% (48 h) at 10 mg/kg. In vivo it reduced both oedema formation and cell infiltration whereas in vitro it reduced the proliferation of activated T-lymphocytes (IC50 of 67.74 microM). Treatment with scropolioside A (100 microM) 18 and 24 h after phytohemagglutinin stimulation increased the number of cells arrested in the subG(0) phase whereas treatment 3 h after stimulation clearly increased the number of cells that passed to the S phase. Scropolioside A also inhibited the production of prostaglandin E2, leukotriene B4, nitric oxide, interleukin-1beta, interleukin-2, interleukin-4, tumour necrosis factor-alpha and interferon-gamma, but had no effect on the production of interleukin-10. Moreover, it modified the expression of both nitric oxide synthase-2 and cyclooxygenase-2, as well as the activation of nuclear factor-kappaB in RAW 264.7 macrophages.
Bas
Esperanza
E
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Av. Vicent Andrés Estellés s/n, 46100-Burjassot, Spain.
Recio
M Carmen
MC
Máñez
Salvador
S
Giner
Rosa M
RM
Escandell
José M
JM
López-Ginés
Concha
C
Ríos
José-Luis
JL
D000485:Allergens; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000276:immunology; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007975:Leukotriene B4 / Q000276:immunology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010081:Oxazolone; D010196:Pancreatic Elastase / Q000276:immunology; D011714:Pyrans / Q000494:pharmacology*; D012756:Sheep; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000485:Allergens; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005960:Glucosides; D008070:Lipopolysaccharides; D011714:Pyrans; C406483:scropolioside A; D010081:Oxazolone; D007975:Leukotriene B4; D010196:Pancreatic Elastase; D053148:Caspase 3; D015232:Dinoprostone