2019
DOI: 10.3389/fphar.2019.00263
|View full text |Cite
|
Sign up to set email alerts
|

Zafirlukast Is a Dual Modulator of Human Soluble Epoxide Hydrolase and Peroxisome Proliferator-Activated Receptor γ

Abstract: Cysteinyl leukotriene receptor 1 antagonists (CysLT1RA) are frequently used as add-on medication for the treatment of asthma. Recently, these compounds have shown protective effects in cardiovascular diseases. This prompted us to investigate their influence on soluble epoxide hydrolase (sEH) and peroxisome proliferator activated receptor (PPAR) activities, two targets known to play an important role in CVD and the metabolic syndrome. Montelukast, pranlukast and zafirlukast inhibited human sEH with IC50 values … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

0
17
0

Year Published

2020
2020
2021
2021

Publication Types

Select...
7
1

Relationship

0
8

Authors

Journals

citations
Cited by 20 publications
(17 citation statements)
references
References 49 publications
0
17
0
Order By: Relevance
“…It is not clear if this was through direct binding to the receptor or as a consequence of indirect effects on cell signalling (Lau, Chow, Au, & Ko, 2011;Mamedova et al, 2005). Similarly, recent findings suggest that zafirlukast can directly activate PPARγ signalling in adipocytes (Gobel et al, 2019). In platelets, PPARγ ligands negatively regulate platelet responses (Moraes et al, 2010).…”
Section: Discussionmentioning
confidence: 99%
“…It is not clear if this was through direct binding to the receptor or as a consequence of indirect effects on cell signalling (Lau, Chow, Au, & Ko, 2011;Mamedova et al, 2005). Similarly, recent findings suggest that zafirlukast can directly activate PPARγ signalling in adipocytes (Gobel et al, 2019). In platelets, PPARγ ligands negatively regulate platelet responses (Moraes et al, 2010).…”
Section: Discussionmentioning
confidence: 99%
“…Zafirlukast had been reported as a competitive leukotriene receptor antagonist for the treatment of bronchial asthma 27 . Moreover, zafirlukast suppressed ROS in chondrocytes as well as used against cardiovascular disease 28,29 . After in vitro antileishmanial analysis, we observed that zafirlukast did not show many promising results as compared to the standard drug.…”
Section: Discussionmentioning
confidence: 87%
“…They elicit a wide range of pro-inflammatory effects, including the expression of adhesion molecules and recruitment and activation of leukocytes [ 38 , 39 ]. In addition to binding leukotriene receptors, LTRAs may have off-target effects; for instance, both montelukast and zafirlukast may inhibit soluble epoxide hydrolase (sEH) and modulate peroxisome proliferator activated receptor γ (PPARγ) at therapeutically relevant plasma concentrations [ 40 ]. These activities may be of benefit in AD; for instance, sEH inhibitors ameliorated AD pathology and improved behavior in the 5xFAD mouse model [ 41 ], and PPARγ agonists reduced cortical and hippocampal amyloid beta levels and improved spatial memory performance in the APP/PS1 mouse model [ 42 ].…”
Section: Discussionmentioning
confidence: 99%