Anti-inflammatory Ingenane Diterpenoids from the Roots of Euphorbia kansui

Abstract

Bioassay-guided fractionation of the ethanolic extract of the roots of <i>Euphorbia kansui</i> led to the isolation of two new ingenane 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 lipopolysaccharide-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 µM, and were more potent than the positive control, quercetin (IC₅₀ = 15.8 µM). Compounds 1: and 5: were selected for further assays toward the key inflammation mediators TNF-<i>α</i> and IL-6, and showed a significant inhibition in a dose-dependent manner. The preliminary mechanistic study revealed that 1: and 5: inhibited NF-<i>κ</i>B activity, which may exert a role in their anti-inflammatory activity.