Inhibition of the Induction of Nitric Oxide Synthase by Kobusin

We isolated a lignan, kobusin from Geranium thunbergii and studied its effect on the expression of inducible nitric oxide synthase (iNOS) gene in a monocyte/macrophage cell line, RAW264.7 cells. Kobusin inhibited lipopolysaccharide (LPS)-stimulated NO production and the expression of iNOS in a concentration-dependent manner. To identify the mechanistic basis for its inhibition of iNOS induction, we examined the effect of kobusin on both the luciferase reporter activity using $NF-{\kappa}B$ minimal promoter and the nuclear translocation of p65. Kobusin suppressed the reporter gene activity and the LPS-induced movement of p65 in to nucleus. $NF-{\kappa}B$ activation is controlled by the phosphorylation and subsequent degradation of $I-{\kappa}B{\alpha}$, and in the present study, we found that $I-{\kappa}B{\alpha}$ phosphorylation was also inhibited by kobusin. Our findings indicate that kobusin may provide a developmental basis for an agent against inflammatory diseases.