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

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