Anti-inflammatory Ingenane Diterpenoids from the Roots of Euphorbia kansui

Bioassay-guided fractionation of the ethanolic extract of the roots of Euphorbia kansui led to the isolation of two new in-genane diterpenoids, euphorkans A (1) and B (2), together with 16 known analogues (3-18). Their structures were determined by combined spectral and chemical methods. All the isolates were evaluated for their inhibitory effects on lipopoly-saccharide-induced nitric oxide production in RAW264.7 macrophage cells. Compounds 1-6 and 10-13 exhibited pronounced inhibitory activity with IC50 values in the range of 2.78-10.6 mu M, and were more potent than the positive control, quercetin (IC50 = 15.8 mu M). Compounds 1 and 5 were selected for further assays toward the key inflammation mediators TNF-alpha and IL-6, and showed a significant inhibition in a dose-dependent manner. The preliminary mechanistic study revealed that 1 and 5 inhibited NF-kappa B activity, which may exert a role in their anti-inflammatory activity.