RESUMO
A series of 2,2-dimethyl-5-[4-(methylsulfonyl)phenyl]-4-phenyl-3(2H)furanones was prepared and evaluated for their ability to inhibit cyclo-oxygenase-2 (COX-2).
Assuntos
Furanos/farmacologia , Isoenzimas/antagonistas & inibidores , Animais , Artrite Experimental/tratamento farmacológico , Técnicas de Química Combinatória , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Doenças do Pé/induzido quimicamente , Doenças do Pé/tratamento farmacológico , Furanos/síntese química , Furanos/química , Concentração Inibidora 50 , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases , Ratos , Ratos Sprague-Dawley , Relação Estrutura-AtividadeRESUMO
An inhibitor on CINC-1 (cytokine-induced neutrophil chemoattractant-1) induction in LPS-stimulated rat kidney epithelioid NRK-52E cells was purified from the roots of Sassurea lappa Clarke, a herbal medicine used in Korean traditional prescriptions for gastric intestinal diseases by a variety of column chromatographic procedures. The inhibitor was identified as reynosin, a sesquiterpene lactone isolated and characterized previously from Ambrosia confertiflora DC., and Magnolia grandiflora L. Reynosin exhibited a dose-dependent inhibition on CINC-1 induction in LPS-stimulated NRK-52E cells, where 50% of inhibitory effect was shown at the concentration of about 1 microM.
Assuntos
Quimiocinas CXC/antagonistas & inibidores , Fatores Quimiotáticos/biossíntese , Substâncias de Crescimento/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular , Lipopolissacarídeos/farmacologia , Plantas Medicinais/química , Sesquiterpenos/farmacologia , Animais , Linhagem Celular , Quimiocina CXCL1 , Quimiocinas CXC/biossíntese , Espectroscopia de Ressonância Magnética , RatosRESUMO
Cytokine-induced neutrophil chemoattractant (CINC), a rat interleukin-8 (IL-8), was quantitated by using a sensitive ELISA. The CINC was induced up to 20 ng/ml from basal 1-2 ng/ml in lipopolysaccharide (LPS)-activated peritoneal macrophages. This CINC induction was significantly inhibited by steroidal anti-inflammatory drugs including dexamethasone, but not by non-steroidal drugs including indomethacin at all. Nine out of 59 herbal medicines which are frequently used in Korean traditional prescriptions for inflammatory diseases exhibited more than 50% of inhibition on the CINC induction by their total methanol extracts with 0.1 mg/ml as a final concentration. The active 9 total extracts were prepared from radix of Aralia continentalis, rhizoma of Cnidium officinale, rhizoma of Coptis chinensis, tuber of Fritillaria verticillata, radix of Saussurea lappa, tuber of Sparganium stoloniferum, flower of Syzygium aromaticum, semen of Trichosanthes kirilowii, and herba of Tripterygium regelii. These total extracts were sequentially fractionated with dichloromethane, ethyl acetate, butanol, and water. Among the solvent-fractionated extracts with 0.05 mg/ml as a final concentration, more than 50% of inhibition on the CINC induction was exhibited by the dichloromethane fraction of Aralia continentalis; the water fraction of Fritillaria verticillata; the dichloromethane fraction of Saussurea lappa; the dichloromethane, ethyl acetate, and butanol fractions of Syzygium aromaticum; the dichloromethane, ethyl acetate, and water fractions of Trichosanthes kirilowii; and the dichloromethane and ethyl acetate fractions of Tripterygium regelii.