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

• Document type: Journal article
• Source: Journal of Natural Products; v. 79, n. 7, p. 1828-1833, JUL 2016.
• Web of Science Citations: 9

Abstract

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)

• FAPESP's process: 12/22378-2 - In vivo and in vitro study of activity of isolated compounds from Brazilian propolis on modulation of neutrophils migration in the inflammatory process
• Grantee: Pedro Luiz Rosalen
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/01365-0 - In vivo and in vitro study of activity of isolated compounds from Brazilian propolis on modulation of neutrophils migration in the inflammatory process
• Grantee: Marcelo Franchin
• Support Opportunities: Scholarships in Brazil - Doctorate