Cinnamoyloxy-mammeisin Isolated from Geopropolis Attenuates Inflammatory Process by Inhibiting Cytokine Production: Involvement of MAPK, AP-1, and NF-kappa B

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Franchin, Marcelo ; Rosalen, Pedro Luiz ; da Cunha, Marcos Guilherme ; Silva, Rangel Leal ; Colon, David F. ; Bassi, Gabriel Shimizu ; de Alencar, Severino Matias ; Ikegaki, Masaharu ; Alves-Filho, Jose C. ; Cunha, Fernando Q. ; Beutler, John A. ; Cunha, Thiago Mattar

• Tipo de documento: Artigo Científico
• Fonte: Journal of Natural Products; v. 79, n. 7, p. 1828-1833, JUL 2016.
• Citações Web of Science: 9

Resumo

Chemical compounds belonging to the class of coumarins have promising anti-inflammatory potential. Cinnamoyloxy-mammeisin (CNM) is a 4-phenylcoumarin that can be isolated from Brazilian geopropolis. To our knowledge, its anti-inflammatory activity has never been studied. Therefore, the present study investigated the anti-inflammatory activity of CNM and elucidated its mechanism of action on isolated macrophages. Pretreatment with CNM reduced neutrophil migration into the peritoneal and joint cavity of mice. Likewise, CNM reduced the in vitro and in vivo release of TNF-alpha and CXCL2/MIP-2. Regarding the possible molecular mechanism of action, CNM reduced the phosphorylation of proteins ERK. 1/2, JNK, p38 MAPK, and AP-1 (subunit c-jun) in PG-stimulated macrophages. Pretreatment with CNM also reduced NF-kappa beta activation in RAW 264.7 macrophages stably expressing the NF-kappa beta-luciferase reporter gene. On the other hand, it did not alter I kappa B alpha degradation or nuclear translocation of p65. Thus, the results of this study demonstrate promising anti-inflammatory activity of CNM and provide an explanation of its mechanism of action in macrophages via inhibition of MAPK signaling, AP-1, and NF-kappa B. (AU)

• Processo FAPESP: 12/22378-2 - Estudo in vivo e in vitro da atividade de compostos isolados de própolis brasileiras sobre a modulação da migração de neutrófilos no processo inflamatório
• Beneficiário: Pedro Luiz Rosalen
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 12/01365-0 - Estudo in vivo e in vitro da atividade de compostos isolados de própolis brasileiras sobre a modulação da migração de neutrófilos no processo inflamatório
• Beneficiário: Marcelo Franchin
• Modalidade de apoio: Bolsas no Brasil - Doutorado