Sesquiterpenoids from <i>Chloranthus anhuiensis</i> with Neuroprotective Effects in PC12 Cells

Abstract

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 EC 50 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.