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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

The effects of scropolioside B and catalpol on LPS-induced expression of IL-32β and IL-32γ in THP-1 cells. THP-1 cells were pretreated with 50 μmol/L catalpol or scropolioside B for 1 h and then stimulated with LPS (1 μg/mL) for another 24 h. The expression of IL-32β and IL-32γ mRNA was measured by RT-PCR. The data represent the mean values of over three experiments ± SD. ##P < 0.01 compared to vehicle control, #P < 0.05 compared to vehicle control, **P < 0.01 compared to LPS alone, and *P < 0.05 compared to LPS alone.
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fig3: The effects of scropolioside B and catalpol on LPS-induced expression of IL-32β and IL-32γ in THP-1 cells. THP-1 cells were pretreated with 50 μmol/L catalpol or scropolioside B for 1 h and then stimulated with LPS (1 μg/mL) for another 24 h. The expression of IL-32β and IL-32γ mRNA was measured by RT-PCR. The data represent the mean values of over three experiments ± SD. ##P < 0.01 compared to vehicle control, #P < 0.05 compared to vehicle control, **P < 0.01 compared to LPS alone, and *P < 0.05 compared to LPS alone.

Mentions: IL-32 is a proinflammatory cytokine involved in several diseases, including infections, chronic inflammation, and cancer. TNF-α or LPS are known inducers of IL-32, IL-32-dependent effects of IL-1β on endothelial cell functions [26]. We next determined the inhibitory effects of scropolioside B on IL-32 expression. Pretreatment with scropolioside B significantly diminished the increase in mRNA expression levels of IL-32β and IL-32γ induced by LPS stimulation (Figures 3(a) and 3(b)), similar to IL-1β and TNF-α expression pattern, in LPS-induced THP-1 cells.


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)

The effects of scropolioside B and catalpol on LPS-induced expression of IL-32β and IL-32γ in THP-1 cells. THP-1 cells were pretreated with 50 μmol/L catalpol or scropolioside B for 1 h and then stimulated with LPS (1 μg/mL) for another 24 h. The expression of IL-32β and IL-32γ mRNA was measured by RT-PCR. The data represent the mean values of over three experiments ± SD. ##P < 0.01 compared to vehicle control, #P < 0.05 compared to vehicle control, **P < 0.01 compared to LPS alone, and *P < 0.05 compared to LPS alone.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: The effects of scropolioside B and catalpol on LPS-induced expression of IL-32β and IL-32γ in THP-1 cells. THP-1 cells were pretreated with 50 μmol/L catalpol or scropolioside B for 1 h and then stimulated with LPS (1 μg/mL) for another 24 h. The expression of IL-32β and IL-32γ mRNA was measured by RT-PCR. The data represent the mean values of over three experiments ± SD. ##P < 0.01 compared to vehicle control, #P < 0.05 compared to vehicle control, **P < 0.01 compared to LPS alone, and *P < 0.05 compared to LPS alone.
Mentions: IL-32 is a proinflammatory cytokine involved in several diseases, including infections, chronic inflammation, and cancer. TNF-α or LPS are known inducers of IL-32, IL-32-dependent effects of IL-1β on endothelial cell functions [26]. We next determined the inhibitory effects of scropolioside B on IL-32 expression. Pretreatment with scropolioside B significantly diminished the increase in mRNA expression levels of IL-32β and IL-32γ induced by LPS stimulation (Figures 3(a) and 3(b)), similar to IL-1β and TNF-α expression pattern, in LPS-induced THP-1 cells.

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