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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.
AuthorsYun-Ji Seo, Kyung-Tae Lee, Jung-Rae Rho, Jung-Hye Choi
JournalMarine drugs (Mar Drugs) Vol. 13 Issue 11 Pg. 7005-19 (Nov 19 2015) ISSN: 1660-3397 [Electronic] Switzerland
PMID26610528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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