Potencial anti-inflamatório de Pyrenocine A isolada do Penicillium paxilli: abordagem profilática e terapêutica
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Data
2013-01-23
Autores
Toledo, Thaís Regina [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Os organismos marinhos da costa brasileira são pouco explorados como fonte de metabólitos secundários para aplicação farmacológica. São conhecidas aproximadamente 10.000 substâncias do metabolismo secundário de invertebrados e microrganismos marinhos. Dentre os organismos marinhos estudados do ponto de vista químico e farmacológico, destacam-se as esponjas, as ascídias, os briozoários e os octocorais. No entanto, pouco se sabe quanto ao potencial imunomodulador de compostos isolados de microrganismos marinhos, em especial da costa brasileira. Neste estudo, nós identificamos o composto DR(A)6 com potencial anti-inflamatório e após fracionamento foi isolado a substância pura majoritária denominada Pyrenocine A (1), oriunda do fungo marinho Penicillium paxill.O conjunto de resultados demonstra que Pyrenocine A é capaz de inibir tanto de maneira profilática como terapêutica a ativação de macrófagos induzida por LPS através da inibição da síntese de nitrito, produção de citocinas inflamatórias e PGE2, porém de maneira independente da modulação de COX- 2. Os efeito supressores desta substância também pode ser comprovado quanto a expressão de moléculas diretamente relacionadas com a migração celular (CD11b) assim como moléculas imprescindíveis para o processo de ativação de linfócitos (B7.1 e B7.2), porém não foi observado a inibição da expressão do receptor TLR4. A inibição da síntese de nitrito pela Pyrenocine A em macrófagos estimulados com CpG, mas não com Poly I:C, sugere que a via de sinalização intracelular pela qual a Pyrenocine A atua é via MyD88. Além disso, nós demonstramos que...
Marine organisms from Brazilian coast are unexploited as a source of secondary metabolites in applying biotechnology. There are approximately 10,000 known substances from the secondary metabolites from microorganisms and marine invertebrates. Among the marine organisms studied from chemical and pharmacological aproauchs sponges, sea squirts, bryozoans and octocorals are the relevant source of drugs. However, little is known about the immunomodulatory potential of compounds isolated from marine microorganisms, in particular from Brazilian coast. In this study, we identified the compound DR (A) 6 with potential anti-inflammatory and after fractionation, we identificated the majority pure substance, called Pyrenocine A (1), derived from the marine fungus Penicillium paxilli. Our results demonstrates that the Pyrenocine A is able to inhibit by both prophylactically and therapeutic approach the macrophages activation induced by LPS through inhibition of nitrite, synthesis of inflammatory cytokines and PGE2 but independently of modulation of COX-2. The anti-inflammatory effect of Pyrenocine A can also be observed by the expression of molecules directly related to cell migration (CD11b) as well as molecules evolved in the process of lymphocyte activation (B7.1 and B7.2), but there was no inhibition of the TLR4 expression. The inhibition of nitrite by Pyrenocine A in macrophages stimulated with CpG, but not in the presence of Poly I: C, suggesting that Pyrenocine A act by MyD88 intracellular signaling pathway. Furthermore, we demonstrate that the addition of Pyrenocine A exert a suppressive effect on cells from innate immune response is also able to inhibit of B cells proliferation. However, the mechanisms by which this compound exerts its anti-inflammatory functions as well as their pharmacological application in various experimental... (Complete abstract click electronic access below)
Marine organisms from Brazilian coast are unexploited as a source of secondary metabolites in applying biotechnology. There are approximately 10,000 known substances from the secondary metabolites from microorganisms and marine invertebrates. Among the marine organisms studied from chemical and pharmacological aproauchs sponges, sea squirts, bryozoans and octocorals are the relevant source of drugs. However, little is known about the immunomodulatory potential of compounds isolated from marine microorganisms, in particular from Brazilian coast. In this study, we identified the compound DR (A) 6 with potential anti-inflammatory and after fractionation, we identificated the majority pure substance, called Pyrenocine A (1), derived from the marine fungus Penicillium paxilli. Our results demonstrates that the Pyrenocine A is able to inhibit by both prophylactically and therapeutic approach the macrophages activation induced by LPS through inhibition of nitrite, synthesis of inflammatory cytokines and PGE2 but independently of modulation of COX-2. The anti-inflammatory effect of Pyrenocine A can also be observed by the expression of molecules directly related to cell migration (CD11b) as well as molecules evolved in the process of lymphocyte activation (B7.1 and B7.2), but there was no inhibition of the TLR4 expression. The inhibition of nitrite by Pyrenocine A in macrophages stimulated with CpG, but not in the presence of Poly I: C, suggesting that Pyrenocine A act by MyD88 intracellular signaling pathway. Furthermore, we demonstrate that the addition of Pyrenocine A exert a suppressive effect on cells from innate immune response is also able to inhibit of B cells proliferation. However, the mechanisms by which this compound exerts its anti-inflammatory functions as well as their pharmacological application in various experimental... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Organismos marinhos, Biologia marinha, Microorganismos, Briozoario, Macrofagos, Linfocitos, Marine biology
Como citar
TOLEDO, Thaís Regina. Potencial anti-inflamatório de Pyrenocine A isolada do Penicillium paxilli: abordagem profilática e terapêutica. 2013. 67 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências Farmacêuticas de Araraquara, 2013.