Anti-inflammatory lanostane triterpenoids with rearranged spirobi[indene] scaffold and their biogenetically related analogues from Euphorbia maculata

Phytochemical investigations on the ethanol extract of the whole plant of Euphorbia maculata Linn. Resulted in the identification of 16 lanostane-related triterpenoids, including 11 undescribed ones, namely spiromaculatols A–C (1–3) and euphomaculatoids A–H (4–11). The structural determinations of the previously undescribed ones (1–11) were elucidated based on the interpretation of comprehensive spectroscopic data, quantum chemical calculation, as well as X-ray crystallographic experiments. Spiromaculatols A–C (1–3) possess a rare spirobi [indane] skeleton, which was biosynthetically derived from the 7 (8 → 9)-abeo bond migration of lanostane precursors. The biological activity of compounds 1–3, 5, 7, and 12–13 displayed inhibitory effect on the release of NO in an LPS-activated RAW264.7 cells model. Molecular mechanism study indicated that the most potent spiromaculatol C (3) can reduce the nuclear translocation of NF-κB p65 and decrease the transcriptional expressions of its downstream pro-inflammatory mediators.