Inhibition of NO production by activated macrophages by phenolcarboxylic acid monomers and polymers with radical scavenging activity.

Phenolcarboxylic acids (caffeic acid, p-coumaric acid, ferulic acid) and their dehydrogenation polymer (DHP) were compared for their ability to inhibit the nitric oxide (NO) production by lipopolysaccharide (LPS)-activated mouse macrophage-like cells Raw 264.7 and to scavenge superoxide (O2-) (generated by hypoxanthine and xanthine oxidase reaction), hydroxyl radical (generated by Fenton reaction) and NO radical (generated by NOC-7), using ESR spectroscopy in vitro. All phenolcarboxylic acids effectively inhibited the NO production by activated Raw 264.7 cells. Among them, caffeic acid showed the highest cytotoxic activity, radical intensity and O2- scavenging activity, but the least NO scavenging activity. Caffeic acid also inhibited the NO production most effectively. Polymers of caffeic acid (DHP-CA) and p-coumaric acid (DHP-pCA) showed higher cytotoxicity, radical intensity and radical scavenging activity and more efficiently inhibited the NO production, as compared with the corresponding monomers. DHP-CA showed higher radical generation and O2- scavenging activity than DHP-pCA. The potent O2- scavenging activity of caffeic acid was probably due to the chemical reaction of O2- to the cathecol groups. Caffeic acid, DHP-CA and DHP-pCA induced the cytotoxicity, possibly due to autogenerating radicals, because these compounds efficiently produced radicals under alkaline conditions. In summary, caffeic acid acted as a polyphenolics in phenylcarboxylic acids. A possible link between cytotoxicity and radical generation of phenylcarboxylic acids is proposed.