A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models.
To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.
Shin
Ki Young
KY
Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea.
Lee
Geon Ho
GH
Park
Cheol Hyoung
CH
Kim
Hee Jin
HJ
Park
Soo-Hyun
SH
Kim
Seonghan
S
Kim
Hye-Sun
HS
Lee
Kwan-Sun
KS
Won
Beom Young
BY
Lee
Hyung Gun
HG
Choi
Jin-Ho
JH
Suh
Yoo-Hun
YH
D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology*; D045304:Cytochromes c / Q000187:drug effects; D003704:Dementia / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D018727:Muscarinic Antagonists / Q000633:toxicity; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012601:Scopolamine / Q000633:toxicity
D016229:Amyloid beta-Peptides; D003373:Coumaric Acids; D018727:Muscarinic Antagonists; D018696:Neuroprotective Agents; D011753:Pyrones; D017382:Reactive Oxygen Species; C524754:maltolyl p-coumarate; C008316:maltol; D045304:Cytochromes c; D012601:Scopolamine; D053148:Caspase 3