title: Cinnamoyloxy-mammeisin Isolated from Geopropolis Attenuates Inflammatory Process by Inhibiting Cytokine Production: Involvement of MAPK, AP-1, and NF-κB.
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-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.
authors.affiliation: Piracicaba Dental School, University of Campinas , Piracicaba, 13414-903, SP, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Franchin
authors.affiliation: Piracicaba Dental School, University of Campinas , Piracicaba, 13414-903, SP, Brazil.
authors.forename: Pedro Luiz
authors.initials: PL
authors.lastname: Rosalen
authors.affiliation: Piracicaba Dental School, University of Campinas , Piracicaba, 13414-903, SP, Brazil.
authors.forename: Marcos Guilherme
authors.initials: MG
authors.lastname: da Cunha
authors.affiliation: Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto, 14049-900, SP, Brazil.
authors.forename: Rangel Leal
authors.initials: RL
authors.lastname: Silva
authors.affiliation: Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto, 14049-900, SP, Brazil.
authors.forename: David F
authors.initials: DF
authors.lastname: Colón
authors.affiliation: Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto, 14049-900, SP, Brazil.
authors.forename: Gabriel Shimizu
authors.initials: GS
authors.lastname: Bassi
authors.affiliation: "Luiz de Queiroz" College of Agriculture, University of São Paulo , Piracicaba, 13418-900 SP, Brazil.
authors.forename: Severino Matias
authors.initials: SM
authors.lastname: de Alencar
authors.affiliation: School of Pharmaceutical Sciences, Federal University of Alfenas , 37715-400, Alfenas, MG, Brazil.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ikegaki
authors.affiliation: Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto, 14049-900, SP, Brazil.
authors.forename: José C
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto, 14049-900, SP, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute , Frederick, Maryland 21702-1201, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Beutler
authors.affiliation: Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto, 14049-900, SP, Brazil.
authors.forename: Thiago Mattar
authors.initials: TM
authors.lastname: Cunha
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001938:Brazil; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019892:eIF-2 Kinase / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C000618150:cinnamoyloxy-mammeisin; C001878:mammeisin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D019892:eIF-2 Kinase; D048051:p38 Mitogen-Activated Protein Kinases