Discovery of guaiane-type sesquiterpenoids from the roots of Daphne genkwa with neuroprotective effects.

A phytochemical study on the roots of Daphne genkwa yielded seven new guaiane-type sesquiterpenoids (1-7), daphne A-G. Their structures were elucidated through comprehensive spectroscopic analyses. The absolute configurations were determined by comparison between experimental electronic circular dichroism (ECD) and calculated ECD spectra via time-dependent density functional theory (TDDFT) and the modified Mosher's method. Furthermore, all isolates were evaluated for their neuroprotective activities against H2O2-induced injury in human neuroblastoma SH-SY5Y cells. Among them, compounds 1 (78.42%) and 4 (79.34%) exhibited potent neuroprotective effects against H2O2-induced neurotoxicity at 25 µM. Further Annexin V-FITC/propidium iodide (PI) doubling staining exhibited that the neuroprotective effects of compounds 1 and 4 appeared to be mediated via suppressing cell apoptosis. Flow cytometry assays also proved that compounds 1 and 4 could attenuate mitochondrial dysfunction in SH-SY5Y cells.