Lathyrane and ent-isopimarane diterpenoids from Euphorbia wallichii and target prediction of active ingredient

Fourteen undescribed diterpenoids, including eleven lathyrane diterpenoids wallathyanes A-K (1–11) and three ent-isopimarane diterpenoids wallisopiranes A-C (12–14), together with fourteen known analogues 15–28, were obtained from the whole plant of Euphorbia wallichii. Their chemical structures were elucidated by spectroscopic data analysis, experimental electronic circular dichroism measurements, and X-ray crystallography. Bioactivity screening indicated that compound 2 exhibited an inhibitory effect on NO generation in LPS-stimulated RAW264.7 macrophage cells with an IC50 value of 4.76 ± 1.08 μM. The network pharmacology and molecular docking studies also revealed that compound 2 can bind with the potential targets GRB, AKT1, MAPK1, MAPK14, HSP90AA1, PIK3R1, PIK3CB, PRKACA, SRC, CASP3, RXRA, PTPNA11, ZAP70, and PRKC of inflammation. Fourteen undescribed diterpenoids, including eleven lathyrane diterpenoids wallathyanes A-K (1–11) and three ent-isopimarane diterpenoids wallisopiranes A-C (12–14), together with fourteen known analogues 15–28, were obtained from the whole plant of Euphorbia wallichii. Bioactivity screening indicated that compound 2 exhibited an inhibitory effect on NO generation in LPS-stimulated RAW264.7 macrophage cells. [Display omitted] •Fourteen previously undescribed diterpenoids were isolated from E. wallichii.•The absolute configuration of 1 was determined by X-ray crystallography.•2 showed marked anti-inflammatory activity with an IC50 value of 4.76 ± 1.08 μM.•The anti-inflammatory targets of 2 were predicted and then docked.