Open AccessCinnamoyloxy-mammeisin Isolated from Geopropolis Attenuates Inflammatory Process by Inhibiting Cytokine Production: Involvement of MAPK, AP-1, and NF-κB
Author(s) -
Marcelo Franchin,
Pedro Luiz Rosalen,
Marcos Guilherme da Cunha,
Rangel L. Silva,
David F. Colón,
Gabriel Shimizu Bassi,
Severino Matias de Alencar,
Masaharu Ikegaki,
José Carlos AlvesFilho,
Fernando Q. Cunha,
John A. Beutler,
Thiago M. Cunha
Publication year - 2016
Publication title -
journal of natural products
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.976
H-Index - 139
eISSN - 1520-6025
pISSN - 0163-3864
DOI - 10.1021/acs.jnatprod.6b00263
Subject(s) - mapk/erk pathway , nf κb , p38 mitogen activated protein kinases , mechanism of action , tumor necrosis factor alpha , in vivo , phosphorylation , iκbα , cytokine , in vitro , microbiology and biotechnology , macrophage , chemistry , luciferase , biology , nfkb1 , kinase , transfection , signal transduction , biochemistry , immunology , gene , transcription factor
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-α 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-κB activation in RAW 264.7 macrophages stably expressing the NF-κB-luciferase reporter gene. On the other hand, it did not alter IκBα 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-κB.