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.
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Authors | Yun-Ji Seo, Kyung-Tae Lee, Jung-Rae Rho, Jung-Hye Choi |
Journal | Marine drugs
(Mar Drugs)
Vol. 13
Issue 11
Pg. 7005-19
(Nov 19 2015)
ISSN: 1660-3397 [Electronic] Switzerland |
PMID | 26610528
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Cytokines
- Inflammation Mediators
- Lipopolysaccharides
- NF-kappa B
- Sesterterpenes
- phorbaketal A
- Nitric Oxide
- Nitric Oxide Synthase Type II
- Heme Oxygenase-1
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Topics |
- Animals
- Anti-Inflammatory Agents
(isolation & purification, pharmacology)
- Cell Line
- Cytokines
(metabolism)
- Down-Regulation
(drug effects)
- Heme Oxygenase-1
(drug effects, metabolism)
- Inflammation
(drug therapy, pathology)
- Inflammation Mediators
(metabolism)
- Lipopolysaccharides
(pharmacology)
- Macrophages
(drug effects, metabolism)
- Mice
- NF-kappa B
(antagonists & inhibitors)
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type II
(metabolism)
- Porifera
(metabolism)
- Sesterterpenes
(isolation & purification, pharmacology)
- Up-Regulation
(drug effects)
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