title: A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Shin
authors.forename: Geon Ho
authors.initials: GH
authors.lastname: Lee
authors.forename: Cheol Hyoung
authors.initials: CH
authors.lastname: Park
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Seonghan
authors.initials: S
authors.lastname: Kim
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Kwan-Sun
authors.initials: KS
authors.lastname: Lee
authors.forename: Beom Young
authors.initials: BY
authors.lastname: Won
authors.forename: Hyung Gun
authors.initials: HG
authors.lastname: Lee
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Yoo-Hun
authors.initials: YH
authors.lastname: Suh
mesh_terms: 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
chemical_list: 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