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Mar. Drugs 2015, 13(11), 7005-7019; doi:10.3390/md13117005

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

1
Department of Life & Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea
2
College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea
3
Department of Marine Biotechnology, Kunsan National University, Jeonbuk 573-701, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Peer B. Jacobson
Received: 5 October 2015 / Accepted: 13 November 2015 / Published: 19 November 2015
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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. View Full-Text
Keywords: phorbaketal A; macrophages; nitric oxide; prostaglandin E2; inflammatory cytokine; NF-κB; HO-1 phorbaketal A; macrophages; nitric oxide; prostaglandin E2; inflammatory cytokine; NF-κB; HO-1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Seo, Y.-J.; Lee, K.-T.; Rho, J.-R.; Choi, J.-H. 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. Mar. Drugs 2015, 13, 7005-7019.

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