Mannasantin B, a dilignan structurally related to manssantin A, is an inhibitor of NF-kB transactivation. In the present study, we found that it inhibited PMA-induced expression of IL-1b, IL-1b mRNA, and IL-1b promoter activity in U937 cells with IC50 values of about 50 nM. It also inhibited NF-IL6- and NF-kB-induced activation of IL-1b, with IC50 values of 78 nM and 1.6 mM, respectively, revealing a potent inhibitory effect on NF-IL6. Electrophoretic mobility shift assays showed that manassantin B had an inhibitory effect on DNA binding by NF-IL6, but not by NF-kB. Further analysis revealed that transactivation by NF-IL6 was also inhibited. Our results indicate that manassantin B suppresses expression of IL-1b in promonocytic cells by inhibiting not only NF-kB but also NF-IL6 activity. Furthermore, our observations suggest that manassantin B may be clinically useful as a potent inhibitor of NF-IL6 activity.

Keywords: C/EBPb, Inhibitors, Manassantin, NF-kB, NF-IL6, Saururus chinensis