New sesquiterpene dimers from Inula britannica inhibit NF-kappaB activation and NO and TNF-alpha production in LPS-stimulated RAW264.7 cells

A bioassay-guided isolation of an ethyl acetate-soluble extract of the aerial parts of Inula britannica var. chinensis (Rupr.) Regel, using an in vitro NF-κB reporter gene assay, led to the isolation of four new sesquiterpene dimers bearing a norbornene moiety, inulanolides A - D (1 - 4), and three known sesquiterpenes, 1,6α-dihydroxyeriolanolide (5), 1-acetoxy-6α-hydroxyeriolanolide (6), and eupatolide (7). The structures of the new compounds were elucidated by spectroscopic methods. Among these compounds, inulanolides B and D (2 and 4) and eupatolide (7), exhibited potent inhibitory activity on the LPS-induced NF-κB activation with IC 50 values of 0.49 pM, 0.48 pM, and 1.54 μM, respectively. Consistent with their inhibitory effect on NF-KB activation, compounds 2, 4, and 7 also strongly inhibited the production of NO and TNF-a in the LPS-stimulated RAW264.7 cells with IC 50 values in the range of 2 pM.