Objective To investigate the terpenoid constituents of fruit shells of Euphorbia peplus and evaluate their anti-inflammatory activities. Methods Various chromatographic techniques were applied to isolate terpenoids from the petroleum ether-soluble fraction of the ethanol extract of E. peplus fruit shells. The chemical structures of all isolates were elucidated by comprehensive spectroscopic analyses (1D/2D NMR, HRMS) combined with single-crystal X-ray diffraction. Anti-inflammatory activities were assessed by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results A total of 13 terpenoids were isolated from the petroleum ether fraction of E. peplus fruit shells, including four paraliane-type diterpenoids (1–4), one pepluane-type diterpenoid (5), three jatrophane-type diterpenoids (6–8), two ingenane-type diterpenoids (9 and 10), one abietane-type diterpenoid (11), one ursane-type triterpenoid (12), and one dinor-monocyclic diterpenoid (13). They were respectively identified as (2S,3S,4R,5R,6R,8S,12S,13S,15R)-8b-acetyl-paralianone D (1), (1R,2R,3S,4R,5R,6R,8S,12S,13S,14R, 15R)-1,5,8,14-tetraacetoxy-3-benzoyloxy-15-hydroxy-9-oxo-paraliane (2), (2S,3S,4R,5R,6R,8S,12S,13S,14R,15R)-5,8,14-triacetoxy-3-benzoyloxy-15-hydroxy-9-oxo-parapliane (3), paralianone A (4), (2S,3S,4R,5R,6R,8R,9R,10R,12S,13S,14R,15R)-5,8,9,10,14-pentaacetoxy-3-benzoyloxy-15-hydroxypepluane (5), euphpepluone A (6), euphpepluone D (7), (2S,3S,4R,5R,7S,8R,13S,15R)-5α,7b,8α-triacetoxy-3b-benzoyloxy-15b-hydroxyjatropha-6(17),11E-diene-9,14-dione (8), 20-deoxyingenol (9), 20-O-(2¢E,4¢Z-decadienoyl)ingenol (10), helioscopinolide D (11), ursolic acid (12) and (3R,6R,7E,9E,11E)-3-hydroxy-13-apo-α-caroten-13-one (13). The structure of compound 1 was confirmed by single-crystal X-ray diffraction. In the anti-inflammatory activity screening, only compound 2 exhibited inhibitory activity against NO production, with an IC₅₀ value of (37.6 ±8.2) μmol/L. Conclusion Compounds 1, 2, 10, and 13 were isolated from E. peplus for the first time. Compound 2 demonstrated moderate anti-inflammatory activity. This study enriches the terpenoid chemical diversity of terpenoids from E. peplus and provides an experimental basis for further research on its anti-inflammatory substances.

Euphorbiaceae  /  Euphorbia peplus Linn.  /  diterpenoids  /  anti-inflammatory  /  20-deoxyingenol  /  ursolic acid  /  8b-acetyl-paralianone D  /  (2S,3S,4R,5R,6R,8S,12S,13S,15R)-8b-acetyl-paralianone D