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PLoS One
2014 Feb 13;92:e88341. doi: 10.1371/journal.pone.0088341.
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Anti-inflammatory effect of unsaturated fatty acids and Ergosta-7,22-dien-3-ol from Marthasterias glacialis: prevention of CHOP-mediated ER-stress and NF-κB activation.
Pereira DM
,
Correia-da-Silva G
,
Valentão P
,
Teixeira N
,
Andrade PB
.
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There has been increasing awareness to the potential interest of drug discovery from marine natural products to treat several pathological conditions, including inflammation. In this work we describe the anti-inflammatory activity of several compounds present in the echinoderm Marthasterias glacialis (spiny sea-star), using the inflammatory model RAW 264.7 cells challenged with LPS. Lipidomic profiling of the organism revealed two major classes of compounds: fatty acids and sterols. Among these, the predominant compounds cis 11-eicosenoic and cis 11,14 eicosadienoic acids and the unsaturated sterol ergosta-7,22-dien-3-ol were evaluated. The mechanism of action of the compounds was distinct as they modulated different levels of the inflammation pathway. Classical inflammatory markers, such as COX-2, iNOS, IL-6 and NF-κB, were evaluated. We also studied the contribution of the CHOP pathway-mediated ER-stress to the inflammatory process. Overall, the sterol ergosta-7,22-dien-3-ol was the most active compound, however maximum activity was obtained when all compounds were tested in combination, thus suggesting a potentially synergistic activity of both classes of metabolites. This work establishes the echinoderm M. glacialis as an interesting source of anti-inflammatory molecules.
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24551093
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Figure 1. Evaluation of the effect of LPS and LPS+extract on cell morphology: A – phase contrast; B – Wright staining. Red arrows: cytoplasmic vesicles (autophagosomes); C - Acridine orange staining of control and LPS-treated macrophages.White arrows: autophagosomes. Incubation with LPS causes the characteristic morphology of activated macrophages, which includes the advent of autophagosomes. Pre-incubation with the extract attenuates the number of autophagosomes. Original magnification: 400×.
Figure 4. Effect of purified extract (156 µg/mL) from M. glacialis (A) and major compounds in the extract (B) in the expression of iNOS, COX-2, CHOP and IKB-α in LPS-treated RAW 264.7 cells.Densitometric analysis of the studied proteins after normalisation to β-tubulin levels. Results are expressed as mean ± SD of three experiments. *P<0.05; **P<0.01; ***P<0.001 (vs LPS). Ext: extract (156 µg/mL); PA: 20 µM palmitic acid; cis
11: 35 µM cis 11-eicosenoic acid; cis
11,14: 10 µM cis 11,14-eicosadienoic acid; E-7,22: 25 µM ergosta-7,22-dien-3-ol. combination: Palmitic acid+cis 11-eicosenoic acid+cis 11,14-eicosadienoic+ergosta-7,22-dien-3-ol.
Figure 6. Proposed mechanism for the anti-inflammatory activity of different compounds present in M. glacialis.
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