Sesquiterpenoids from Chloranthus anhuiensis with Neuroprotective Effects in PC12 Cells

Glutamate-induced excito­toxicity plays a vital role in neuro­degenerative diseases. Neuroprotection against excito­toxicity has been considered as an effective experimental approach for preventing and/or treating excito­toxicity-mediated diseases. In the present study, six new sesqui­terpenoids (1–6) and 26 known compounds of this type (7–32) were isolated and characterized from the whole plants of Chloranthus anhuiensis. Chlorantolide A (1) is the first example of a 5,6-seco-germacrane-type sesqui­terpenoid, while phacadinane E (2) is a rare 4,5-seco-cadinane-type sesqui­terpenoid. The structures of the new compounds were determined by spectroscopic analysis and by calculations of electronic circular dichroism (ECD) spectra. Their neuro­protective effects in mediating glutamate-induced PC12 cell apoptosis were evaluated. Compound 26 exhibited potent neuroprotective activity with an EC₅₀ value of 3.3 ± 0.9 μM. Using Hoechst 33258 staining, a caspase-3 activity assay, and Western blot analysis it was demonstrated that this compound reduces the apoptosis of PC12 cells through inhibition of caspase-3 activity, while activating the Akt signaling pathway.