Sesquiterpenoids from Chloranthus anhuiensis with Neuroprotective Effects in PC12 Cells
2018
Xu, Jian | Zhu, Hui-Lin | Zhang, Jie | Du, Tao | Guo, Er-Yan | Liu, Wenyuan | Luo, Jian-Guang | Ye, Feng | Feng, Feng | Qu, Wei
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.
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