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Sesquiterpenoids from Chloranthus anhuiensis with Neuroprotective Effects in PC12 Cells

Xu, Jian, Zhu, Hui-Lin, Zhang, Jie, Du, Tao, Guo, Er-Yan, Liu, Wen-Yuan, Luo, Jian-Guang, Ye, Feng, Feng, Feng, Qu, Wei
Journal of natural products 2018 v.81 no.6 pp. 1391-1398
Chloranthus, Western blotting, apoptosis, caspase-3, circular dichroism spectroscopy, median effective concentration, neurodegenerative diseases, neuroprotective effect, sesquiterpenoids, signal transduction, spectral analysis, staining
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.