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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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Scropolioside B and catalpol inhibited the expression of CLS1 and NLRP3 in LPS-induced THP-1 cells. ((a)-(b)) The effects of scropolioside B and catalpol on protein expression of NLRP3 in LPS-induced THP-1 cells. ((c)-(d)) 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 protein expression of NLRP3 was measured by western blot. The expression of CLS1 and NLRP3 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, and **P < 0.01 compared to LPS alone.
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fig4: Scropolioside B and catalpol inhibited the expression of CLS1 and NLRP3 in LPS-induced THP-1 cells. ((a)-(b)) The effects of scropolioside B and catalpol on protein expression of NLRP3 in LPS-induced THP-1 cells. ((c)-(d)) 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 protein expression of NLRP3 was measured by western blot. The expression of CLS1 and NLRP3 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, and **P < 0.01 compared to LPS alone.

Mentions: Inflammasomes regulate maturation of IL-1β and IL-18 and pyroptosis. NLRP3 is a member of inflammasomes which constitute the compound with ASC and caspase-1 to catalyze the maturation of IL-1β [27]. To observe whether inflammatory factors induce NLRP3 expression, we stimulated THP-1 cells with LPS for 24 h. We observed that LPS upregulated NLRP3 mRNA and protein (Figures 4(a), 4(c), and 4(d)). Similarly, LPS also significantly enhanced mRNA expression of cardiolipin synthetase 1 (CLS1) (Figure 4(b)), a mitochondrial enzyme catalysing cardiolipin synthesis necessary for inflammasome NLRP3 activity [28]. As shown in Figures 4(a)–4(d), pretreatment with scropolioside B inhibited the expressions of NLRP3 mRNA and protein, as well as CLS1 mRNA. We also found that catalpol was as equally effective as scropolioside B (Figures 4(a)–4(d)), suggesting that this inhibitory effect may be from the same catalpol structure (Figure 6).


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 and catalpol inhibited the expression of CLS1 and NLRP3 in LPS-induced THP-1 cells. ((a)-(b)) The effects of scropolioside B and catalpol on protein expression of NLRP3 in LPS-induced THP-1 cells. ((c)-(d)) 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 protein expression of NLRP3 was measured by western blot. The expression of CLS1 and NLRP3 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, and **P < 0.01 compared to LPS alone.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4216717&req=5

fig4: Scropolioside B and catalpol inhibited the expression of CLS1 and NLRP3 in LPS-induced THP-1 cells. ((a)-(b)) The effects of scropolioside B and catalpol on protein expression of NLRP3 in LPS-induced THP-1 cells. ((c)-(d)) 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 protein expression of NLRP3 was measured by western blot. The expression of CLS1 and NLRP3 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, and **P < 0.01 compared to LPS alone.
Mentions: Inflammasomes regulate maturation of IL-1β and IL-18 and pyroptosis. NLRP3 is a member of inflammasomes which constitute the compound with ASC and caspase-1 to catalyze the maturation of IL-1β [27]. To observe whether inflammatory factors induce NLRP3 expression, we stimulated THP-1 cells with LPS for 24 h. We observed that LPS upregulated NLRP3 mRNA and protein (Figures 4(a), 4(c), and 4(d)). Similarly, LPS also significantly enhanced mRNA expression of cardiolipin synthetase 1 (CLS1) (Figure 4(b)), a mitochondrial enzyme catalysing cardiolipin synthesis necessary for inflammasome NLRP3 activity [28]. As shown in Figures 4(a)–4(d), pretreatment with scropolioside B inhibited the expressions of NLRP3 mRNA and protein, as well as CLS1 mRNA. We also found that catalpol was as equally effective as scropolioside B (Figures 4(a)–4(d)), suggesting that this inhibitory effect may be from the same catalpol structure (Figure 6).

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