title: Phorbaketal A, Isolated from the Marine Sponge Phorbas sp., Exerts Its Anti-Inflammatory Effects via NF-κB Inhibition and Heme Oxygenase-1 Activation in Lipopolysaccharide-Stimulated Macrophages.
abstract: Marine sponges harbor a range of biologically active compounds. Phorbaketal A is a tricyclic sesterterpenoid isolated from the marine sponge Phorbas sp.; however, little is known about its biological activities and associated molecular mechanisms. In this study, we examined the anti-inflammatory effects and underlying molecular mechanism of phorbaketal A in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that phorbaketal A significantly inhibited the LPS-induced production of nitric oxide (NO), but not prostaglandin E₂, in RAW 264.7 cells. Further, phorbaketal A suppressed the expression of inducible NO synthase at both the mRNA and protein levels. In addition, phorbaketal A reduced the LPS-induced production of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and monocyte chemotactic protein-1. Treatment with phorbaketal A inhibited the transcriptional activity of nuclear factor-kappaB (NF-κB), a crucial signaling molecule in inflammation. Moreover, phorbaketal A up-regulated the expression of heme oxygenase-1 (HO-1) in LPS-stimulated RAW 264.7 cells. These data suggest that phorbaketal A, isolated from the marine sponge Phorbas sp., inhibits the production of inflammatory mediators via down-regulation of the NF-κB pathway and up-regulation of the HO-1 pathway.
authors.affiliation: Department of Life & Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea. syg9108@khu.ac.kr.|College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea. syg9108@khu.ac.kr.
authors.forename: Yun-Ji
authors.initials: YJ
authors.lastname: Seo
authors.affiliation: Department of Life & Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea. ktlee@khu.ac.kr.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Department of Marine Biotechnology, Kunsan National University, Jeonbuk 573-701, Korea. jrrho@kunsan.ac.kr.
authors.forename: Jung-Rae
authors.initials: JR
authors.lastname: Rho
authors.affiliation: Department of Life & Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea. jchoi@khu.ac.kr.|College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea. jchoi@khu.ac.kr.
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011161:Porifera / Q000378:metabolism; D054830:Sesterterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D054830:Sesterterpenes; C546752:phorbaketal A; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1
keywords: HO-1; NF-κB; inflammatory cytokine; macrophages; nitric oxide; phorbaketal A; prostaglandin E2