Discovery of anti-inflammatory terpenoids from Mallotus conspurcatus croizat

Mallotus conspurcatus croizat (Euphorbiaceae), a plant native to Jinxiu in Guangxi, is popularly used in folk medicine to treat pelvic inflammatory disease. The anti-inflammatory activities of the compounds obtained from M. conspurcatus root were evaluated in this study.

This study explored the major anti-inflammatory components of this plant.

The ethyl acetate fraction of the ethanol extract from M. conspurcatus was separated using chromatographic techniques. The structures of the isolates were elucidated from NMR, MS and X-ray data as well as from ECD. The anti-inflammatory activities of the isolates from M. conspurcatus were evaluated using LPS-stimulated RAW 264.7 cell models. The production of NO, TNF-α and PGE-2 was determined by ELISA and Griess tests. The expression levels of COX-2, NF-κB/p65 and iNOS were measured by western blotting.

Two new diterpenoids, malloconspur A (1) and malloconspur B (2), and sixteen known terpenoids (3-18) were identified by comprehensive spectroscopic analyses and comparison with literature data. Malloconspur B (2) and 17-hydroxycleistantha-12,15-dien-3-one (3) substantially inhibited the release of NO with IC₅₀ values of 10.47 μM and 9.32 μM, respectively. Compounds 1, 2 and 3 markedly decreased the secretion of PGE₂ and TNF-α (P < 0.01) by LPS-induced RAW264.7 cells. Compounds 2 and 3 markedly decreased iNOS, NF-κB/p65 and COX-2 protein expression.

Our identification of these diterpenoids provides strong evidence for the use of M. conspurcatus among the Yao people as a medicinal plant for the treatment of inflammation. The dramatic differences in the chemical structures of the active diterpenoids of this plant from those on the market suggest these compounds have potential as anti-inflammatory lead compounds for follow-up research.