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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.

Seo YJ, Lee KT, Rho JR, Choi JH - Mar Drugs (2015)

Bottom Line: We found that phorbaketal A significantly inhibited the LPS-induced production of nitric oxide (NO), but not prostaglandin E₂, in RAW 264.7 cells.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.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 Article: PubMed Central - PubMed

Affiliation: Department of Life & Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea. syg9108@khu.ac.kr.

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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Effects of phorbaketal A on the expression of pro-inflammatory cytokines in LPS-stimulated RAW 264.7 cells. (A–D) RAW 264.7 cells were pretreated with different concentrations of phorbaketal A (2.5, 5, and 10 μM) for 1 h and then stimulated with LPS (1 μg/mL) for 8 h. The mRNA levels of tumor necrosis factor-alpha (TNF-α) (A); interleukin-1beta (IL-1β) (B); IL-6 (C); and monocyte chemotactic protein-1 (MCP-1) (D) were determined by real-time RT-PCR. Data are presented as the means ± SD of three independent experiments. Statistical analysis was carried out using the one-way ANOVA followed by the Tukey’s test. #p < 0.05 vs. CTRL group. * p < 0.05 vs. LPS-stimulated group.
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marinedrugs-13-07005-f003: Effects of phorbaketal A on the expression of pro-inflammatory cytokines in LPS-stimulated RAW 264.7 cells. (A–D) RAW 264.7 cells were pretreated with different concentrations of phorbaketal A (2.5, 5, and 10 μM) for 1 h and then stimulated with LPS (1 μg/mL) for 8 h. The mRNA levels of tumor necrosis factor-alpha (TNF-α) (A); interleukin-1beta (IL-1β) (B); IL-6 (C); and monocyte chemotactic protein-1 (MCP-1) (D) were determined by real-time RT-PCR. Data are presented as the means ± SD of three independent experiments. Statistical analysis was carried out using the one-way ANOVA followed by the Tukey’s test. #p < 0.05 vs. CTRL group. * p < 0.05 vs. LPS-stimulated group.

Mentions: Upon activation, macrophages promote inflammatory processes via the release of diverse pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and MCP-1 [2,30]. TNF-α, IL-1β, and IL-6 are elevated in most inflammatory states and are known targets of anti-inflammatory therapeutic agents [31]. MCP-1 has been suggested to induce monocyte recruitment [32]. We investigated the effect of phorbaketal A on the LPS-induced expression of TNF-α, IL-1β, IL-6, and MCP-1 using real-time RT-PCR in RAW 264.7 cells. As shown in Figure 3, treatment with phorbaketal A markedly suppressed the expression of TNF-α, IL-1β, IL-6, and MCP-1 in a dose-dependent manner.


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.

Seo YJ, Lee KT, Rho JR, Choi JH - Mar Drugs (2015)

Effects of phorbaketal A on the expression of pro-inflammatory cytokines in LPS-stimulated RAW 264.7 cells. (A–D) RAW 264.7 cells were pretreated with different concentrations of phorbaketal A (2.5, 5, and 10 μM) for 1 h and then stimulated with LPS (1 μg/mL) for 8 h. The mRNA levels of tumor necrosis factor-alpha (TNF-α) (A); interleukin-1beta (IL-1β) (B); IL-6 (C); and monocyte chemotactic protein-1 (MCP-1) (D) were determined by real-time RT-PCR. Data are presented as the means ± SD of three independent experiments. Statistical analysis was carried out using the one-way ANOVA followed by the Tukey’s test. #p < 0.05 vs. CTRL group. * p < 0.05 vs. LPS-stimulated group.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4663563&req=5

marinedrugs-13-07005-f003: Effects of phorbaketal A on the expression of pro-inflammatory cytokines in LPS-stimulated RAW 264.7 cells. (A–D) RAW 264.7 cells were pretreated with different concentrations of phorbaketal A (2.5, 5, and 10 μM) for 1 h and then stimulated with LPS (1 μg/mL) for 8 h. The mRNA levels of tumor necrosis factor-alpha (TNF-α) (A); interleukin-1beta (IL-1β) (B); IL-6 (C); and monocyte chemotactic protein-1 (MCP-1) (D) were determined by real-time RT-PCR. Data are presented as the means ± SD of three independent experiments. Statistical analysis was carried out using the one-way ANOVA followed by the Tukey’s test. #p < 0.05 vs. CTRL group. * p < 0.05 vs. LPS-stimulated group.
Mentions: Upon activation, macrophages promote inflammatory processes via the release of diverse pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and MCP-1 [2,30]. TNF-α, IL-1β, and IL-6 are elevated in most inflammatory states and are known targets of anti-inflammatory therapeutic agents [31]. MCP-1 has been suggested to induce monocyte recruitment [32]. We investigated the effect of phorbaketal A on the LPS-induced expression of TNF-α, IL-1β, IL-6, and MCP-1 using real-time RT-PCR in RAW 264.7 cells. As shown in Figure 3, treatment with phorbaketal A markedly suppressed the expression of TNF-α, IL-1β, IL-6, and MCP-1 in a dose-dependent manner.

Bottom Line: We found that phorbaketal A significantly inhibited the LPS-induced production of nitric oxide (NO), but not prostaglandin E₂, in RAW 264.7 cells.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.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 Article: PubMed Central - PubMed

Affiliation: Department of Life & Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Korea. syg9108@khu.ac.kr.

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.

Show MeSH
Related in: MedlinePlus