Joshi, Vikram and Venkatesha, Shivaprasad H. and Chandrasekaran, R. and Nanjaraj Urs, A. N. and Hiremath, Vilas and Moudgil, Kamal D. and Velmurugan, Devadasan and Vishwanath, B. S. (2016) Celastrol modulates inflammation through inhibition of the catalytic activity of mediators of arachidonic acid pathway: Secretory phospholipase A2 group IIA, 5-lipoxygenase and cyclooxygenase-2. Pharmacological Research, 113 (Part A). 265 - 275.
Full text not available from this repository. (Request a copy)Abstract
Elevated production of arachidonic acid (AA)-derived pro-inflammatory eicosanoids due to the concerted action of secretory phospholipase A2 group IIA (sPLA2IIA), 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) is a common feature of many inflammatory disorders. Hence, modulation of the bioactivity of these 3 enzymes is an important strategy to control inflammation. However, the failure of drugs specific for an individual enzyme (sPLA2IIA-, 5-LOX- or COX-2) and the success of 5-LOX/COX-2 dual inhibitors in effectively controlling inflammation in clinical trials prompted us to evaluate a common inhibitor for sPLA2IIA, 5-LOX and COX-2 enzymes. Celastrol, a quinone methide triterpene, was selected in this regard through molecular docking studies. We provide the first evidence for celastrol’s ability to inhibit the catalytic activity of sPLA2IIA, 5-LOX and COX-2 enzymes. Celastrol significantly inhibited the catalytic activity of sPLA2IIA (IC50=6μM) in vitro, which is independent of substrate and calcium concentration. In addition, celastrol inhibited the catalytic activities of 5-LOX (IC50=5μM) and COX-2 (IC50=20μM) in vitro; sPLA2IIA-induced edema and carrageenan-induced edema in mice; and lipopolysaccharide-stimulated production of PGE2 in human neutrophils. Thus, celastrol modulates inflammatory responses by targeting multiple enzymes of AA pathway.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Inflammation, Arachidonic acid, Cyclooxygenase, Lipoxygenase, Phospholipase A, Celastrol |
| Subjects: | B Life Science > Biotechnology |
| Divisions: | Department of > Biochemistry |
| Depositing User: | Manjula P Library Assistant |
| Date Deposited: | 30 May 2019 11:25 |
| Last Modified: | 16 Nov 2019 10:21 |
| URI: | http://eprints.uni-mysore.ac.in/id/eprint/706 |
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