7-(4-Hydroxyphenyl)-1-phenyl-4E-hepten-3-one, a Diarylheptanoid from Alpinia officinarum, Protects Neurons against Amyloid-β Induced Toxicity.
Amyloid-β (Aβ) is one of the major causative agents of Alzheimer's disease (AD), the most common neurodegenerative disorder characterized by progressive cognitive impairment. While effective drugs for AD are currently limited, identifying anti-Aβ compounds from natural products has been shown as a promising strategy which may lead to breakthroughs for new drug candidate discovery. We have previously reported that 7-(4-hydroxyphenyl)-1-phenyl-4E-hepten-3-one (AO-1), a diarylheptanoid extracted from the plant Alpinia officinarum, has strong effects on neuronal differentiation and neurite outgrowth in vitro and in vivo. The present study further uncovers that AO-1 exerts neuroprotective effects against the neurotoxicity caused by Aβ. Under the damage of Aβ oligomers, the major pathological forms of Aβ, dendrites of neurons become atrophic and simplified, but such impairments were substantially alleviated by AO-1 treatment. Moreover, AO-1 reduced apoptotic levels and oxidative stress triggered by Aβ. Further analysis showed that the anti-caspase and dendrite protective effects of AO-1 were dependent on activation of phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathways. These findings collectively identify AO-1 as a beneficial compound to ameliorate the deleterious effects of Aβ on dendrite integrity and cell survival, and may provide new insights on drug discovery of AD.
JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University.
Xiaojie
X
Huang
Genyun
G
Tang
Yumei
Y
Liao
Xiaoji
X
Zhuang
Xiao
X
Dong
Hui
H
Liu
Xiao-Jun
XJ
Huang
Wen-Cai
WC
Ye
Ying
Y
Wang
Lei
L
Shi
D032429:Alpinia; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D006536:Heptanes / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity*; D010636:Phenols / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D016229:Amyloid beta-Peptides; D053148:Caspase 3; D006536:Heptanes; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases; C000614034:7-(4-hydroxyphenyl)-1-phenyl-4E-hepten-3-one; C075222:amyloid beta-protein (1-42); C546845:mTOR protein, rat