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Scropolioside B inhibits IL-1β and cytokines expression through NF-κB and inflammasome NLRP3 pathways.

Zhu T, Zhang L, Ling S, Duan J, Qian F, Li Y, Xu JW - Mediators Inflamm. (2014)

Bottom Line: However, catalpol, similar to scropolioside B, was not effective in inhibiting NF-κB activity.Our results showed that scropolioside B is superior in inhibiting the expression, maturation, and secretion of IL-1β compared to catalpol.These observations provide further understanding of the anti-inflammatory effects of iridoids and highlight scropolioside B as a potential drug for the treatment of rheumatoid arthritis and atherosclerosis.

View Article: PubMed Central - PubMed

Affiliation: Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China ; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

ABSTRACT
Chronic inflammation is associated with various chronic illnesses including immunity disorders, cancer, neurodegeneration, and vascular diseases. Iridoids are compounds with anti-inflammatory properties. However their anti-inflammatory mechanism remains unclear. Here, we report that scropolioside B, isolated from a Tibetan medicine (Scrophularia dentata Royle ex Benth.), blocked expressions of TNF, IL-1, and IL-32 through NF-κB pathway. Scropolioside B inhibited NF-κB activity in a dose-dependent manner with IC50 values of 1.02 μmol/L. However, catalpol, similar to scropolioside B, was not effective in inhibiting NF-κB activity. Interestingly, scropolioside B and catalpol decreased the expression of NLRP3 and cardiolipin synthetase at both the mRNA and protein level. Our results showed that scropolioside B is superior in inhibiting the expression, maturation, and secretion of IL-1β compared to catalpol. These observations provide further understanding of the anti-inflammatory effects of iridoids and highlight scropolioside B as a potential drug for the treatment of rheumatoid arthritis and atherosclerosis.

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Related in: MedlinePlus

Scropolioside B inhibited TNF-α-induced NF-κB activation. Cells were preincubated for 1 hour with different doses of scropolioside B and then stimulated with 1 μg/mL TNF-α for 16 hours. The results shown are representative of 3 separate experiments. Data are expressed as means ± SD. #P < 0.05 versus the control, *P < 0.05 versus the TNF-α (a). IC50 values of 1.02 μmol/L (b).
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fig2: Scropolioside B inhibited TNF-α-induced NF-κB activation. Cells were preincubated for 1 hour with different doses of scropolioside B and then stimulated with 1 μg/mL TNF-α for 16 hours. The results shown are representative of 3 separate experiments. Data are expressed as means ± SD. #P < 0.05 versus the control, *P < 0.05 versus the TNF-α (a). IC50 values of 1.02 μmol/L (b).

Mentions: NF-κB is an essential transcription factor involved in the production of several cytokines that mediate the inflammatory response. To investigate overall anti-inflammatory activity of scropolioside B, we used a luciferase reporter assay to determine nuclear factor kappa B (NF-κB) activity. After HEK293 cells were transferred with either the NF-κB or the control plasmid, cells were treated with or without scropolioside B for 1 h and then stimulated with 100 ng/mL of TNF-α. An increase in luciferase activity was observed after stimulation with TNF-α, suggesting that NF-κB was activated by TNF-α (Figure 2(a)). Pretreatment with scropolioside B (0.08–50 μmol/L) inhibited TNF-α-induced NF-κB activation in a concentration-dependent manner. Furthermore, scropolioside B exhibited an IC50 value of 1.02 μmol/L (Figure 2(b)). These results showed that scropolioside B-mediated inhibition of inflammatory cytokine induction was due to the suppression of NF-κB.


Scropolioside B inhibits IL-1β and cytokines expression through NF-κB and inflammasome NLRP3 pathways.

Zhu T, Zhang L, Ling S, Duan J, Qian F, Li Y, Xu JW - Mediators Inflamm. (2014)

Scropolioside B inhibited TNF-α-induced NF-κB activation. Cells were preincubated for 1 hour with different doses of scropolioside B and then stimulated with 1 μg/mL TNF-α for 16 hours. The results shown are representative of 3 separate experiments. Data are expressed as means ± SD. #P < 0.05 versus the control, *P < 0.05 versus the TNF-α (a). IC50 values of 1.02 μmol/L (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4216717&req=5

fig2: Scropolioside B inhibited TNF-α-induced NF-κB activation. Cells were preincubated for 1 hour with different doses of scropolioside B and then stimulated with 1 μg/mL TNF-α for 16 hours. The results shown are representative of 3 separate experiments. Data are expressed as means ± SD. #P < 0.05 versus the control, *P < 0.05 versus the TNF-α (a). IC50 values of 1.02 μmol/L (b).
Mentions: NF-κB is an essential transcription factor involved in the production of several cytokines that mediate the inflammatory response. To investigate overall anti-inflammatory activity of scropolioside B, we used a luciferase reporter assay to determine nuclear factor kappa B (NF-κB) activity. After HEK293 cells were transferred with either the NF-κB or the control plasmid, cells were treated with or without scropolioside B for 1 h and then stimulated with 100 ng/mL of TNF-α. An increase in luciferase activity was observed after stimulation with TNF-α, suggesting that NF-κB was activated by TNF-α (Figure 2(a)). Pretreatment with scropolioside B (0.08–50 μmol/L) inhibited TNF-α-induced NF-κB activation in a concentration-dependent manner. Furthermore, scropolioside B exhibited an IC50 value of 1.02 μmol/L (Figure 2(b)). These results showed that scropolioside B-mediated inhibition of inflammatory cytokine induction was due to the suppression of NF-κB.

Bottom Line: However, catalpol, similar to scropolioside B, was not effective in inhibiting NF-κB activity.Our results showed that scropolioside B is superior in inhibiting the expression, maturation, and secretion of IL-1β compared to catalpol.These observations provide further understanding of the anti-inflammatory effects of iridoids and highlight scropolioside B as a potential drug for the treatment of rheumatoid arthritis and atherosclerosis.

View Article: PubMed Central - PubMed

Affiliation: Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China ; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

ABSTRACT
Chronic inflammation is associated with various chronic illnesses including immunity disorders, cancer, neurodegeneration, and vascular diseases. Iridoids are compounds with anti-inflammatory properties. However their anti-inflammatory mechanism remains unclear. Here, we report that scropolioside B, isolated from a Tibetan medicine (Scrophularia dentata Royle ex Benth.), blocked expressions of TNF, IL-1, and IL-32 through NF-κB pathway. Scropolioside B inhibited NF-κB activity in a dose-dependent manner with IC50 values of 1.02 μmol/L. However, catalpol, similar to scropolioside B, was not effective in inhibiting NF-κB activity. Interestingly, scropolioside B and catalpol decreased the expression of NLRP3 and cardiolipin synthetase at both the mRNA and protein level. Our results showed that scropolioside B is superior in inhibiting the expression, maturation, and secretion of IL-1β compared to catalpol. These observations provide further understanding of the anti-inflammatory effects of iridoids and highlight scropolioside B as a potential drug for the treatment of rheumatoid arthritis and atherosclerosis.

Show MeSH
Related in: MedlinePlus