Prenylated Polyphenols from Broussonetia kazinoki as Inhibitors of Nitric Oxide Production

Abstract

Excessive nitric oxide (NO) production by macrophages has been involved in inflammatory diseases. Seven polyphenols (1-7) were isolated from Broussonetia kazinoki (B. kazinoki) and investigated as potential inhibitors of NO overproduction in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Among them, four prenylated polyphenols (2-4 and 6) with a catechol moiety efficiently suppressed the LPS-induced high level of NO with IC50 values of less than 6 mu M. The compounds 2-4 and 6 also attenuated protein and mRNA levels of inducible nitric oxide synthase (iNOS). Moreover, they suppressed the nuclear factor kappa B (NF-kappa B) activity by inhibiting the degradation of inhibitory-kappa B-alpha (I-kappa B-alpha) and the translocation of NF-kappa B into the nucleus in LPS-activated macrophages. Taken together, these findings suggest that polyphenols from B. kazinoki might be beneficial for treatment of inflammatory diseases.