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RISS 인기검색어
- 검색키워드
- 저자 : Carolina N. Fuzissaki (검색결과 2 건)
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Fla´via V. Santa-Cecı´lia,Ge´rsika B. Santos,Carolina N. Fuzissaki,Priscilla B.M.C. Derogis,Lissara A.S. Freitas,Vanessa S. Gontijo,Paulo C. Stringheta,Tanus J. Nagem,Maı´sa R.P.L. Brigaga˜o,Marcelo H 한국식품영양과학회 2012 Journal of medicinal food Vol.15 No.2
Despite defenses by polymorphonuclear neutrophils in the host against invading agents, overproduction of oxidant species by phagocytes can lead to damage in the surrounding tissues. Several benzophenones have been shown to possess anti-inflammatory properties. The effect of the natural benzophenone 7-epiclusianone isolated from leaves of Garcinia brasiliensis was investigated by using in vitro antioxidant and ex vivo anti-inflammatory assays, focusing on the neutrophil respiratory burst and on the biochemical pathways involved. The bioactive extract, 7-epiclusianone, showed low in vitro antioxidant activity as evaluated by the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, the reducing power test,or the chelating power assay. However, the benzophenone displayed potent activity in the ex vivo model of the neutrophil respiratory burst, inhibiting the generation of superoxide anions in a dose-dependent manner. When the respiratory burst was triggered by N-formyl-methionyl-leucyl-phenylalanine, a chemotactic peptide, the 50% effective concentration (EC50) was 41.18 lg/107 cells. When phagocytes were stimulated directly through protein kinase C via phorbol, the EC50 was 34.3 lg/106cells. The results indicated that 7-epiclusianone was able to down-regulate inflammatory phagocyte superoxide anion release through a mechanism controlled by tyrosine protein phosphorylation and by a direct stimulation of protein kinase C. These findings could lead to new therapeutic approaches for inflammation management and the development of new drugs.
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4-Methylcoumarin Derivatives Inhibit Human Neutrophil Oxidative Metabolism and Elastase Activity
Luciana M. Kabeya,Carolina N. Fuzissaki,Mica´ssio F. Andrade,Ana Elisa C.S. Azzolini,Silvia H. Taleb-Contini,Roberta B. Vermelho,Joa˜o Luis C. Lopes,Yara Maria Lucisano-Valim 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.8
Increased neutrophil activation significantly contributes to the tissue damage in inflammatory illnesses; this phenomenon has motivated the search for new compounds to modulate their effector functions. Coumarins are natural products that are widely consumed in the human diet. We have evaluated the antioxidant and immunomodulator potential of five 4-methylcoumarin derivatives. We found that the 4-methylcoumarin derivatives inhibited the generation of reactive oxygen species by human neutrophils triggered by serum-opsonized zymosan or phorbol-12-myristate-13-acetate; this inhibition occurred in a concentration-dependent manner, as revealed by lucigenin- and luminol-enhanced chemiluminescence assays. Cytotoxicity did not mediate this inhibitory effect. The 7,8-dihydroxy-4-methylcoumarin suppressed the neutrophil oxidative metabolism more effectively than the 6,7- and 5,7-dihydroxy-4-methylcoumarins, but the 5,7- and 7,8-diacetoxy-4-methylcoumarins were less effective than their hydroxylated counterparts. An analysis of the biochemical pathways suggested that the 6,7- and 7,8-dihydroxy-4-methylcoumarins inhibit the protein kinase C-mediated signaling pathway, but 5,7-dihydroxy-4-methylcoumarin, as well as 5,7- and 7,8-diacetoxy-4-methylcoumarins do not significantly interfere in this pathway of the activation of the human neutrophil oxidative metabolism. The 4-methylcoumarin derivatives bearing the catechol group suppressed the elastase and myeloperoxidase activity and reduced the 1,1-diphenyl-2-picrylhydrazyl free radical the most strongly. Interestingly, the 5,7-dihydroxy-4-methylcoumarin scavenged hypochlorous acid more effectively than the o-dihydroxy-substituted 4-methylcoumarin derivatives, and the diacetoxylated 4-methylcoumarin derivatives scavenged hypochlorous acid as effectively as the 7,8-dihydroxy-4-methylcoumarin. The significant influence of small structural modifications in the inhibitory potential of 4-methylcoumarin derivatives on the effector functions of neutrophil makes them interesting candidates to develop new drugs for the treatment of inflammatory diseases mediated by increased neutrophil activation.
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