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Pharmacological mechanism underlying anti-inflammatory properties of two structurally divergent coumarins through the inhibition of pro-inflammatory enzymes and cytokines

Overview of attention for article published in Journal of Inflammation, July 2015
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Title
Pharmacological mechanism underlying anti-inflammatory properties of two structurally divergent coumarins through the inhibition of pro-inflammatory enzymes and cytokines
Published in
Journal of Inflammation, July 2015
DOI 10.1186/s12950-015-0087-y
Pubmed ID
Authors

Salman Khan, Omer Shehzad, Mao-Sheng Cheng, Rui-Juan Li, Yeong Shik Kim

Abstract

The aim of the present study is to investigate the effects of two structurally divergent coumarins, calipteryxin (1) and (3'S,4'S)-3',4'-disenecioyloxy-3',4'-dihydroseselin (2) from Seseli recinosum, in lipopolysaccharide (LPS)-stimulated murine macrophages. The nitrite production was evaluated using Griess reagent. The protein and mRNA expression levels were investigated through Western blot and quantitative real time-PCR analyses. The NF-κB and AP-1 DNA-binding activities were assessed using an electrophoretic mobility shift assay. The docking studies were performed with Glide XP in Schrödinger suite (version 2013). The results of the present study revealed that calipteryxin (1) and (3'S,4'S)-3',4'-disenecioyloxy-3',4'-dihydroseselin (2) treatment showed potent inhibitory effects on pro-inflammatory enzymes and cytokines associated with molecular signaling pathways. Treatment with calipteryxin and (3'S,4'S)-3',4'-disenecioyloxy-3',4'-dihydroseselin also decreased the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in a dose-dependent manner. Additionally, both coumarins inhibited the LPS-induced protein and mRNA expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 cells. To explore the potential mechanisms underlying the inhibitory activity of coumarin derivatives, the protein signaling pathways for NF-κB, mitogen-activated protein kinase (MAPK) and Akt were examined. Calipteryxin and (3'S,4'S)-3',4'-disenecioyloxy-3',4'-dihydroseselin markedly reduced the LPS-stimulated phosphorylation of IKKα/β, p-IκBα and IκBα degradation as well as the nuclear translocation of the p65 subunit of pro-inflammatory transcription factor NF-κB. In addition, calipteryxin and (3'S,4'S)-3',4'-disenecioyloxy-3',4'-dihydroseselin) considerably inhibited the LPS-induced expression of ERK, c-Jun N-terminal kinase (JNK), p38 and Akt proteins. Furthermore, both coumarins significantly inhibited c-Jun expression in the nucleus. Taken together, these results support the therapeutic potential and molecular mechanism of calipteryxin and (3'S,4'S)-3',4'-disenecioyloxy-3',4'-dihydroseselin associated with inflammatory diseases.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 39%
Student > Bachelor 4 22%
Professor 1 6%
Student > Ph. D. Student 1 6%
Unspecified 1 6%
Other 1 6%
Unknown 3 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 4 22%
Pharmacology, Toxicology and Pharmaceutical Science 3 17%
Medicine and Dentistry 2 11%
Chemistry 2 11%
Biochemistry, Genetics and Molecular Biology 1 6%
Other 4 22%
Unknown 2 11%

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 29 July 2015.
All research outputs
#3,815,934
of 5,422,321 outputs
Outputs from Journal of Inflammation
#96
of 149 outputs
Outputs of similar age
#131,244
of 189,508 outputs
Outputs of similar age from Journal of Inflammation
#6
of 8 outputs
Altmetric has tracked 5,422,321 research outputs across all sources so far. This one is in the 16th percentile – i.e., 16% of other outputs scored the same or lower than it.
So far Altmetric has tracked 149 research outputs from this source. They receive a mean Attention Score of 2.3. This one is in the 14th percentile – i.e., 14% 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 189,508 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 8 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.