Identification of plumericin from Himatanthus Sucuuba as a novel potent inhibitor of the NF-κB pathway directly targeting IKK-β

Himatanthus sucuuba (Spruce) Woodson (Apocynaceae) has been traditionally used in South America to treat inflammatory diseases. Fractions from H. sucuuba have been shown to possess anti-inflammatory activity in vivo.¹ However, the active principles and involved targets remained unknown. Bioactivity-guided fractionation of bark material led to the isolation of 11 compounds.² By X-ray single crystal structure analysis the absolute configuration of one, plumeridoid C (1), was determined. Moreover, NMR experiments showed that 1 crystallizes from methanol, whereas in solution its 3C-epimer is gradually formed and coexistent. All 11 isolated natural products were analyzed for their anti-inflammatory activities. The most potent activity was exerted by the spirolactone iridoid plumericin (2) which was identified as a novel potent NF-κB inhibitor (IC₅₀ 1.1µM) directly targeting IKK-β. Its exceptional potency of action and in vivo efficacy rank plumericin among the most interesting natural products described to date as NF-κB pathway blockers.

Supported by the TWF and the FWF (NFN- S10703, S10704, and S10713). ¹de Miranda, A. L. P. et al. (2000) Planta Med. 66: 284–286. ²Waltenberger, B. et al. (2011) Acta Cryst. C67: o409-o412.