Sesquiterpenoids from Chloranthus anhuiensis with Neuroprotective Effects in PC12 Cells

  • J Nat Prod. 2018 Jun 22;81(6):1391-1398. doi: 10.1021/acs.jnatprod.7b01076.
Jian Xu  1 ,  Hui-Lin Zhu  1 ,  Jie Zhang  1 ,  Tao Du  1 ,  Er-Yan Guo  1 ,  Wen-Yuan Liu  2 ,  Jian-Guang Luo  1 ,  Feng Ye  1 ,  Feng Feng  1  3  4 ,  Wei Qu  1  3
Affiliations
  • 1. Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy , China Pharmaceutical University , Nanjing 210009 , People's Republic of China.
  • 2. Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education , China Pharmaceutical University , Nanjing 210009 , People's Republic of China.
  • 3. Key Laboratory of Biomedical Functional Materials , China Pharmaceutical University , Nanjing 211198 , People's Republic of China.
  • 4. Jiangsu Food & Pharmaceutical Science College , Huaian 223003 , People's Republic of China.
PMID: 29775304 DOI: 10.1021/acs.jnatprod.7b01076
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 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.