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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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 33 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 8 24%
Student > Master 7 21%
Researcher 4 12%
Student > Ph. D. Student 2 6%
Student > Doctoral Student 2 6%
Other 3 9%
Unknown 7 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 15%
Chemistry 5 15%
Pharmacology, Toxicology and Pharmaceutical Science 4 12%
Medicine and Dentistry 3 9%
Biochemistry, Genetics and Molecular Biology 2 6%
Other 5 15%
Unknown 9 27%
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 29 July 2015.
All research outputs
#20,657,128
of 25,374,917 outputs
Outputs from Journal of Inflammation
#278
of 425 outputs
Outputs of similar age
#201,513
of 275,428 outputs
Outputs of similar age from Journal of Inflammation
#8
of 10 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 425 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 7th percentile – i.e., 7% of its peers scored the same or lower than it.
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