Affiliations: UAB Botanicals Research Group, University of Alabama
at Birmingham, Birmingham, AL 35233, USA | School of Chemistry, University of St. Andrews, Fife,
Scotland, UK
Note: [] Corresponding author: Victor M. Darley-Usmar, Department of
Pathology, Molecular and Cellular Division, University of Alabama at
Birmingham, Volker Hall Room GO38, 1670 University Boulevard, Birmingham,
Alabama 35294-0019, USA. Tel.: +1 205 975 9686; Fax: +1 205 934 1775; E-mail:
[email protected]
Abstract: Dietary polyphenolics such as those in soy or red wine can have
beneficial effects on the development of chronic human diseases. The mechanisms
of action of isoflavones have been diverse and include their roles as weak
estrogens, inhibitors of tyrosine kinase-dependent signal transduction
processes and as antioxidants. Recent insights into the oxidative stress model
of atherosclerosis suggest an interesting synthesis of these concepts. Sites of
inflammation are associated with the formation of complex mixtures of reactive
oxygen, nitrogen and halogenating species capable of modifying both endogenous
biomolecules and polyphenolics. Of particular significance are the halogenation
reactions mediated by myeloperoxidase that can modify key amino acids such as
arginine and polyphenolics such as genistein. Hypochlorite, the reaction
product of myeloperoxidase can halogenate polyphenolics to form stable
derivatives with modified biological activity. Thus the {\it in situ}
metabolism at sites of inflammation is unique and generates novel
pharmacophores with potentially distinct modes of action from the parent
compounds.
Journal: BioFactors, vol. 15, no. 2-4, pp. 79-81, 2001
