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

Abstract

A bioassay-guided isolation of an ethyl acetate-soluble extract of the aerial parts of Inula britannica van 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 IC50 values of 0.49 μM, 0.48 μM, and 1.54 μM, respectively. Consistent with their inhibitory effect on NF-κB activation, compounds 2,4, and 7 also strongly inhibited the production of NO and TNF-α in the LPS-stimulated RAW264.7 cells with IC50 values in the range of 2 μM.