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Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects Mice against Bacterial Sepsis

Overview of attention for article published in Frontiers in Pharmacology, January 2018
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Title
Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects Mice against Bacterial Sepsis
Published in
Frontiers in Pharmacology, January 2018
DOI 10.3389/fphar.2017.00975
Pubmed ID
Authors

Yi Liu, Yan-Yun Jing, Chen-Ying Zeng, Chen-Guang Li, Li-Hui Xu, Liang Yan, Wen-Jing Bai, Qing-Bing Zha, Dong-Yun Ouyang, Xian-Hui He

Abstract

The NLRP3 inflammasome plays a critical role in mediating the innate immune defense against pathogenic infections, but aberrant activation of NLRP3 inflammasome has been linked to a variety of inflammatory diseases. Thus targeting the NLRP3 inflammasome represents a promising therapeutic for the treatment of such diseases. Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz. and has been reported to exhibit potent anti-inflammatory activities, but the underlying mechanism is only partly understood. In this study, we aimed to investigate whether scutellarin could affect the activation of NLRP3 inflammasome in macrophages. The results showed that scutellarin dose-dependently reduced caspase-1 activation and decreased mature interleukin-1β (IL-1β) release in lipopolysaccharide (LPS)-primed macrophages upon ATP or nigericin stimulation, indicating that scutellarin inhibited NLRP3 inflammasome activation in macrophages. Consistent with this, scutellarin also suppressed pyroptotic cell death in LPS-primed macrophages treated with ATP or nigericin. ATP or nigericin-induced ASC speck formation and its oligomerization were blocked by scutellarin pre-treatment. Intriguingly, scutellarin augmented PKA-specific phosphorylation of NLRP3 in LPS-primed macrophages, which was completely blocked by selective PKA inhibitor H89, suggesting that PKA signaling had been involved in the action of scutellarin to suppress NLRP3 inflammasome activation. Supporting this, the inhibitory effect of scutellarin on NLRP3 inflammasome activation was completely counteracted by H89 or adenyl cyclase inhibitor MDL12330A. As NLRP3-dependent release of IL-1β has a critical role in sepsis, the in vivo activity of scutellarin was assayed in a mouse model of bacterial sepsis, which was established by intraperitoneally injection of a lethal dose of viable Escherichia coli. Oral administration of scutellarin significantly improved the survival of mice with bacterial sepsis. In line with this, scutellarin treatment significantly reduced serum IL-1β levels and attenuated the infiltration of inflammatory cells in the liver of E. coli-infected mice. These data indicated that scutellarin suppressed NLRP3 inflammasome activation in macrophages by augmenting PKA signaling, highlighting its potential therapeutic application for treating NLRP3-related inflammatory diseases.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 20%
Student > Master 7 16%
Researcher 5 11%
Student > Doctoral Student 3 7%
Student > Bachelor 3 7%
Other 4 9%
Unknown 14 31%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 20%
Agricultural and Biological Sciences 6 13%
Medicine and Dentistry 5 11%
Immunology and Microbiology 4 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 7%
Other 3 7%
Unknown 15 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 January 2018.
All research outputs
#18,581,651
of 23,015,156 outputs
Outputs from Frontiers in Pharmacology
#8,380
of 16,330 outputs
Outputs of similar age
#331,486
of 443,107 outputs
Outputs of similar age from Frontiers in Pharmacology
#141
of 256 outputs
Altmetric has tracked 23,015,156 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,330 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 443,107 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 256 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.