PLA(2) mediated arachidonate free radicals: PLA(2) inhibition and neutralization of free radicals by anti-oxidants - A new role as anti-inflammatory molecule

Nanda, B. L. and Nataraju, A. and Rajesh, R. and Rangappa, K. S. and Shekar, M. A. and Vishwanath, B. S. (2007) PLA(2) mediated arachidonate free radicals: PLA(2) inhibition and neutralization of free radicals by anti-oxidants - A new role as anti-inflammatory molecule. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 7 (8). pp. 765-777.

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Abstract

PLA(2) enzyme catalyses the hydrolysis of cellular phospholipids at the sn-2 position to liberate arachidonic acid and lysophospholipid to generate a family of pro-inflammatory eicosanoids and platelet activating factor. The generation of pro-inflammatory eicosanoids involves a series of free radical intermediates with simultaneous release of reactive oxygen species (superoxide and hydroxyl radicals). Reactive oxygen species formed during arachidonic acid metabolism generates lipid peroxides and the cytotoxic products such as 4-hydroxy nonenal and acrolein, which induces cellular damage. Thus PLA(2) catalyzes the rate-limiting step in the production of pro-inflammatory eicosanoids and free radicals. These peroxides and reactive oxygen species in turn activates PLA(2) enzyme and further attenuates the inflammatory process. Therefore scavenging these free radicals and inhibition of PLA2 enzyme simultaneously by a single molecule such as antioxidants is of great therapeutic relevance for the development of anti-inflammatory molecules. PLA(2) enzymes have been classified into calcium dependent cPLA(2) and sPLA(2) and calcium independent iPLA(2) forms. In several inflammatory diseases sPLA(2) group IIA is the most abundant isoform identified. This isoform is therefore targeted for the development of anti-inflammatory molecules. Many secondary metabolites from plants and marine sponges exhibit both anti-inflammatory and antioxidant properties. Some of them include flavonoids, terpenes and alkaloids. But in terms of PLA(2) inhibition and antioxidant activity, the structural aspects of flavonoids are well studied rather than terpenes and alkaloids. In this line, molecules having both anti-oxidant and PLA(2) inhibitions are reviewed. A single molecule with dual activities may prove to be a powerful anti-inflammatory drug.

Item Type: Article
Subjects: Agriculture Biological Sciences > Biochemistry
University of Mysore > PG Campuses > Manasagangotri, Mysore > Agriculture Biological Sciences > Biochemistry

Physical Sciences > Chemistry
Divisions: PG Campuses > Manasagangotri, Mysore > Biochemistry
PG Campuses > Manasagangotri, Mysore > Chemistry
Depositing User: Users 7 not found.
Date Deposited: 16 Apr 2013 07:03
Last Modified: 06 May 2013 09:24
URI: http://eprints.uni-mysore.ac.in/id/eprint/4566

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