Inhibition of NF-IL6 activity by manassantin B, a dilignan isolated from Saururus chinensis, in phorbol myristate acetate-stimulated U937 promonocytic cells

Abstract

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