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Oleifolioside A, a New Active Compound, Attenuates LPS-Stimulated iNOS and COX-2 Expression through the Downregulation of NF-κB and MAPK Activities in RAW 264.7 Macrophages.

Yu HY, Kim KS, Lee YC, Moon HI, Lee JH - Evid Based Complement Alternat Med (2012)

Bottom Line: Oleifolioside A, a new triterpenoid compound isolated from Dendropanax morbifera Leveille (D. morbifera), was shown in this study to have potent inhibitory effects on lipopolysaccharide (LPS-)stimulated nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages.These results were found to be associated with the inhibition of the degradation and phosphorylation of IκB-α and subsequent translocation of the NF-κB p65 subunit to the nucleus.Taken together, our results suggest that oleifolioside A has the potential to be a novel anti-inflammatory agent capable of targeting both the NF-κB and MAPK signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: College of Natural Resources and Life Science, BK21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714, Republic of Korea.

ABSTRACT
Oleifolioside A, a new triterpenoid compound isolated from Dendropanax morbifera Leveille (D. morbifera), was shown in this study to have potent inhibitory effects on lipopolysaccharide (LPS-)stimulated nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Consistent with these findings, oleifolioside A was further shown to suppress the expression of LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxigenase-2 (COX-2) in a dose-dependent manner at both the protein and mRNA levels and to significantly inhibit the DNA-binding activity and transcriptional activity of NF-κB in response to LPS. These results were found to be associated with the inhibition of the degradation and phosphorylation of IκB-α and subsequent translocation of the NF-κB p65 subunit to the nucleus. Inhibition of NF-κB activation by oleifolioside A was also shown to be mediated through the prevention of p38 MAPK and ERK1/2 phosphorylation. Taken together, our results suggest that oleifolioside A has the potential to be a novel anti-inflammatory agent capable of targeting both the NF-κB and MAPK signaling pathways.

No MeSH data available.


Effects of oleifoliosides A on LPS-stimulated iNOS and COX-2 expression. (a) Cells were pretreated with the indicated concentrations of oleifoliosides A 1 h before LPS (500 ng/mL) treatment for 24 h. The cell lysates were used to determine iNOS and COX-2 protein levels by Western blot assay. (b) After LPS treatment for 6 h, the levels of iNOS and COX-2 mRNA were determined by RT-PCR. GAPDH and β-actin were used as internal controls for Western blot and RT-PCR assays, respectively, n = 6 per experiment.
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fig2: Effects of oleifoliosides A on LPS-stimulated iNOS and COX-2 expression. (a) Cells were pretreated with the indicated concentrations of oleifoliosides A 1 h before LPS (500 ng/mL) treatment for 24 h. The cell lysates were used to determine iNOS and COX-2 protein levels by Western blot assay. (b) After LPS treatment for 6 h, the levels of iNOS and COX-2 mRNA were determined by RT-PCR. GAPDH and β-actin were used as internal controls for Western blot and RT-PCR assays, respectively, n = 6 per experiment.

Mentions: In an attempt to assess whether the inhibition of NO and PGE2 production by oleifolioside A was related to the downregulation of iNOS and COX-2, we next examined the expression levels of these enzymes by Western blotting and quantitative RT-PCR. As shown in Figure 2(a), both iNOS and COX-2 protein levels greatly increased in LPS-stimulated cells when compared to the controls. However, this induction was significantly inhibited in a dose-dependent manner by treatment with oleifolioside A. In particular, the level of iNOS protein was almost completely suppressed when cells were treated with 15 μM oleifolioside A. Similarly, when the effect of oleifolioside A treatment on iNOS and COX-2 mRNA expression in LPS-stimulated RAW 264.7 macrophages was examined by quantitative RT-PCR, a corresponding decrease in iNOSandCOX-2mRNAs was observed (Figure 2(b)). These results suggest that the inhibitory effects of oleifolioside A on LPS-stimulated iNOS and COX-2 expression levels were responsible for the inhibition of NO and PGE2 production observed in these cells.


Oleifolioside A, a New Active Compound, Attenuates LPS-Stimulated iNOS and COX-2 Expression through the Downregulation of NF-κB and MAPK Activities in RAW 264.7 Macrophages.

Yu HY, Kim KS, Lee YC, Moon HI, Lee JH - Evid Based Complement Alternat Med (2012)

Effects of oleifoliosides A on LPS-stimulated iNOS and COX-2 expression. (a) Cells were pretreated with the indicated concentrations of oleifoliosides A 1 h before LPS (500 ng/mL) treatment for 24 h. The cell lysates were used to determine iNOS and COX-2 protein levels by Western blot assay. (b) After LPS treatment for 6 h, the levels of iNOS and COX-2 mRNA were determined by RT-PCR. GAPDH and β-actin were used as internal controls for Western blot and RT-PCR assays, respectively, n = 6 per experiment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Effects of oleifoliosides A on LPS-stimulated iNOS and COX-2 expression. (a) Cells were pretreated with the indicated concentrations of oleifoliosides A 1 h before LPS (500 ng/mL) treatment for 24 h. The cell lysates were used to determine iNOS and COX-2 protein levels by Western blot assay. (b) After LPS treatment for 6 h, the levels of iNOS and COX-2 mRNA were determined by RT-PCR. GAPDH and β-actin were used as internal controls for Western blot and RT-PCR assays, respectively, n = 6 per experiment.
Mentions: In an attempt to assess whether the inhibition of NO and PGE2 production by oleifolioside A was related to the downregulation of iNOS and COX-2, we next examined the expression levels of these enzymes by Western blotting and quantitative RT-PCR. As shown in Figure 2(a), both iNOS and COX-2 protein levels greatly increased in LPS-stimulated cells when compared to the controls. However, this induction was significantly inhibited in a dose-dependent manner by treatment with oleifolioside A. In particular, the level of iNOS protein was almost completely suppressed when cells were treated with 15 μM oleifolioside A. Similarly, when the effect of oleifolioside A treatment on iNOS and COX-2 mRNA expression in LPS-stimulated RAW 264.7 macrophages was examined by quantitative RT-PCR, a corresponding decrease in iNOSandCOX-2mRNAs was observed (Figure 2(b)). These results suggest that the inhibitory effects of oleifolioside A on LPS-stimulated iNOS and COX-2 expression levels were responsible for the inhibition of NO and PGE2 production observed in these cells.

Bottom Line: Oleifolioside A, a new triterpenoid compound isolated from Dendropanax morbifera Leveille (D. morbifera), was shown in this study to have potent inhibitory effects on lipopolysaccharide (LPS-)stimulated nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages.These results were found to be associated with the inhibition of the degradation and phosphorylation of IκB-α and subsequent translocation of the NF-κB p65 subunit to the nucleus.Taken together, our results suggest that oleifolioside A has the potential to be a novel anti-inflammatory agent capable of targeting both the NF-κB and MAPK signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: College of Natural Resources and Life Science, BK21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714, Republic of Korea.

ABSTRACT
Oleifolioside A, a new triterpenoid compound isolated from Dendropanax morbifera Leveille (D. morbifera), was shown in this study to have potent inhibitory effects on lipopolysaccharide (LPS-)stimulated nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Consistent with these findings, oleifolioside A was further shown to suppress the expression of LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxigenase-2 (COX-2) in a dose-dependent manner at both the protein and mRNA levels and to significantly inhibit the DNA-binding activity and transcriptional activity of NF-κB in response to LPS. These results were found to be associated with the inhibition of the degradation and phosphorylation of IκB-α and subsequent translocation of the NF-κB p65 subunit to the nucleus. Inhibition of NF-κB activation by oleifolioside A was also shown to be mediated through the prevention of p38 MAPK and ERK1/2 phosphorylation. Taken together, our results suggest that oleifolioside A has the potential to be a novel anti-inflammatory agent capable of targeting both the NF-κB and MAPK signaling pathways.

No MeSH data available.