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

Shasha Ji, Yun Lei, Xiaotian Huang, Zhiqin Gao

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)582-589
Number of pages8
JournalJournal of Chinese Pharmaceutical Sciences
Volume25
Issue number8
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Sesquiterpenes
Celastrus
Alzheimer Disease
Oxidative Stress
Apoptosis
Neuroprotective Agents
Biological Products
Neuroblastoma
Amyloid
Caspase 3
Disease Progression
Reactive Oxygen Species
Cell Survival
Seeds
Staining and Labeling
Neurons
Pharmaceutical Preparations
Proteins
dihydroagarofuran
Therapeutics

Keywords

  • Alzheimer's disease
  • Apoptosis
  • Neuroprotection
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Protective effects of β-dihydroagarofuran-type sesquiterpene against Aβ25-35-induced neuronal apoptosis and oxidative damage. / Ji, Shasha; Lei, Yun; Huang, Xiaotian; Gao, Zhiqin.

In: Journal of Chinese Pharmaceutical Sciences, Vol. 25, No. 8, 01.01.2016, p. 582-589.

Research output: Contribution to journalArticle

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