Diterpenoids and sesquiterpenoids from Euphorbia helioscopia and their neuroprotective activity.

Euphorbia helioscopia L., also known as "Zeqi" in China, has been used for decades as a traditional Chinese medicine to treat various diseases. In this study, a phytochemical investigation of the whole plant of E. helioscopia resulted in the isolation and structural elucidation of two undescribed lathyrane-type diterpenoids, euphohelioscopids A (1) and B (2), and one unreported megastigmane-type sesquiterpenoid, euphohelioscopid C (3), along with 20 known congeners (4-23). Their structures with absolute configurations were elucidated, based on a combination of extensive spectroscopic data analyses, ECD, and calculated NMR with the STS strategy, as well as comparison with previously reported NMR data. The isolated compounds were evaluated for their neuroprotective activities against glutamate-induced damage in HT22 cells. Compounds 1, 3, 5-8, 13, and 17 exhibited varying degrees of neuroprotective effects. Notably, compound 1, at a low concentration of 5 μM, demonstrated potent activity comparable to that of the positive control, D/L-3-n-butylphthalide (racemic NBP), elevating the cell survival rate from 48.4 % to 82.6 %. Further biological evaluations, including flow cytometric analysis and assessments of the expression of apoptosis-related proteins Bcl-2 and Bax, revealed that compound 1 mitigated glutamate-induced neuronal cell death through an anti-apoptotic pathway. These findings suggested that compound 1 may serve as a valuable lead scaffold for the development of novel neuroprotective agents.