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Journal of Chinese Pharmaceutical Sciences ›› 2016, Vol. 25 ›› Issue (8): 582-589.DOI: 10.5246/jcps.2016.08.065

• Original articles • Previous Articles     Next Articles

Protective effects of β-dihydroagarofuran-type sesquiterpene against Aβ25-35-induced neuronal apoptosis and oxidative damage

Shasha Ji1, Yun Lei2, Xiaotian Huang2*, Zhiqin Gao1*   

  1. 1. School of Biological Science and Technology, Weifang Medical University, Weifang 261053, China
    2. CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
  • Received:2016-04-14 Revised:2016-04-27 Online:2016-09-01 Published:2016-05-14
  • Contact: Tel.: +86-21-50806710, E-mail: zhiqingao2013@163.com, xthuang@simm.ac.cn
  • Supported by:
    National Natural Science Foundation of China (Grant No. 81473113).

Abstract:

Excessive beta-amyloid (Aβ) plays a detrimental role in the pathogenesis of Alzheimer’s disease (AD), which is closely associated with apoptosis and oxidative stress in neurons. Therefore, identification of active small molecules with potent effects on neutralizing Aβ-induced neurotoxicity would be a promising strategy for delaying or preventing AD progression. In the present study, we discovered that pretreatment with CF-1 ((1R,2S,4R,5S,7R,9S,10S)-1,15-diacetoxy-2-benzoyloxy-9-cinnamoyloxy-β-di-hydroagarofuran), a sesquiterpene isolated from the seeds of Celastrus flagellaris, attenuated Aβ25-35-induced reduction in cell viability in a concentration-dependent manner, as evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Above neuroprotective effect of CF-1 was associated with a significant decrease of apoptotic cells as measured by 4,6-diamidino-2-phenylindole (DAPI) staining, which concurrently happened with marked inhibition in the level of cleaved Caspase-3, an apoptotic executive protein. CF-1 pretreatment also markedly reduced the intracellular accumulation of reactive oxygen species (ROS) following Aβ exposure in SH-SY5Y neuroblastoma cells, but such pretreatment had no notable influence on 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging. In conclusion, we demonstrated that a novel natural product, CF-1, possessed promising effects against Aβ-induced neuronal apoptosis and oxidative stress, which could be a potential drug lead or candidate for the treatment of Aβ-associated neurotoxicity.

Key words: Alzheimer’s disease, Aβ, Neuroprotection, Apoptosis, Oxidative stress

CLC Number: 

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