Inhibitory mechanism of chroman compound on LPS-induced nitric oxide production and nuclear factor-kappaB activation.

6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (KL-1156) is a novel chemically synthetic compound. In the present study, the chroman KL-1156 compound was found to inhibit lipopolysaccharide (LPS)-induced nitric oxide production in macrophages RAW 264.7. KL-1156 compound attenuated LPS-induced synthesis of both mRNA and protein of inducible nitric oxide synthase (iNOS), in parallel, and inhibited LPS-induced iNOS promoter activity, indicating that the chroman compound down-regulated iNOS expression at transcription level. As a mechanism of the anti-inflammatory action shown by KL-1156 compound, suppression of nuclear factor (NF)-kappaB has been documented. KL-1156 compound exhibited a dose-dependent inhibitory effect on LPS-induced NF-kappaB transcriptional activity in macrophages RAW 264.7. Furthermore, the compound inhibited LPS-induced nuclear translocation of NF-kappaB p65 and DNA binding activity of NF-kappaB complex, in parallel, but did not affect IkappaBalpha degradation. Taken together, this study demonstrated that chroman KL-1156 compound interfered with nuclear translocation step of NF-kappaB p65, which was attributable to its anti-inflammatory action.