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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

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Department of Life & Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea
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College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea
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Department of Marine Biotechnology, Kunsan National University, Jeonbuk 573-701, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Peer B. Jacobson
Mar. Drugs 2015, 13(11), 7005-7019; https://doi.org/10.3390/md13117005
Received: 5 October 2015 / Accepted: 13 November 2015 / Published: 19 November 2015
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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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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