Inhibitory effect of 6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide on nitric oxide and interleukin-6 production in macrophages.

ABSTRACT

6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (CP compound) is a novel chemically synthetic compound with vitamin E-like chemical structure. In the present study, the CP compound was discovered to inhibit nitric oxide (NO) and interleukin (IL)-6 productions in lipopolysaccharide (LPS)-stimulated macrophages. Further, CP compound attenuated LPS-induced synthesis of mRNA and protein levels of inducible NO synthase (iNOS), in parallel, and inhibited iNOS promoter activity. In the similar way, CP compound inhibited LPS-induced synthesis of IL-6 transcript but also IL-6 promoter activity. These results indicate that CP compound could down-regulate LPS-induced iNOS and IL-6 expression at the transcription step. As a mechanism of the anti-inflammatory action shown by CP compound, suppression of LPS-induced activation of both nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) has been documented. Finally, CP compound could provide an invaluable tool to investigate LPS-induced NF-kappaB and AP-1 activation, in addition to its therapeutic potential in NO- and IL-6-associated inflammatory diseases.