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

• Published in: Journal of natural products (Washington, D.C.) Vol. 79; no. 7; pp. 1828 - 1833
• Main Authors: Franchin, Marcelo, Rosalen, Pedro Luiz, da Cunha, Marcos Guilherme, Silva, Rangel Leal, Colón, David F, Bassi, Gabriel Shimizu, de Alencar, Severino Matias, Ikegaki, Masaharu, Alves-Filho, José C, Cunha, Fernando Q, Beutler, John A, Cunha, Thiago Mattar
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 22.07.2016
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Brazil; Coumarins - chemistry; Coumarins - isolation & purification; Coumarins - pharmacology; Cyclooxygenase 2 - metabolism; eIF-2 Kinase - drug effects; Lipopolysaccharides - pharmacology; Macrophages - metabolism; Mice; Molecular Structure; NF-kappa B - antagonists & inhibitors; Nitric Oxide Synthase Type II - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Signal Transduction - drug effects; Transcription Factor AP-1; Tumor Necrosis Factor-alpha - pharmacology
• DOI: 10.1021/acs.jnatprod.6b00263
• ISSN: 0163-3864; 1520-6025

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.