TY - JOUR
T1 - Protective effects of β-dihydroagarofuran-type sesquiterpene against Aβ25-35-induced neuronal apoptosis and oxidative damage
AU - Ji, Shasha
AU - Lei, Yun
AU - Huang, Xiaotian
AU - Gao, Zhiqin
N1 - Publisher Copyright:
� 2016 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Apoptosis
KW - Aβ
KW - Neuroprotection
KW - Oxidative stress
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UR - http://www.scopus.com/inward/citedby.url?scp=84991442137&partnerID=8YFLogxK
U2 - 10.5246/jcps.2016.08.065
DO - 10.5246/jcps.2016.08.065
M3 - Article
AN - SCOPUS:84991442137
SN - 1003-1057
VL - 25
SP - 582
EP - 589
JO - Journal of Chinese Pharmaceutical Sciences
JF - Journal of Chinese Pharmaceutical Sciences
IS - 8
ER -