A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models

Authors

  • Ki Young Shin,

    1. 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
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    • K.Y. Shin and G.H. Lee contributed equally to this work.

  • Geon Ho Lee,

    1. 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
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    • K.Y. Shin and G.H. Lee contributed equally to this work.

  • Cheol Hyoung Park,

    1. 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
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  • Hee Jin Kim,

    1. 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
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  • Soo-Hyun Park,

    1. Faculty of Food Science and Biotechnology, Pukyong National University, Busan, Korea
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  • Seonghan Kim,

    1. 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
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  • Hye-Sun Kim,

    1. 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
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  • Kwan-Sun Lee,

    1. Central Research Institute, Hanmi Pharmaceutical Company, Gyeonggi-do, Korea
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  • Beom Young Won,

    1. Braintropia Company, Gyeonggi-do, Korea
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  • Hyung Gun Lee,

    1. Braintropia Company, Gyeonggi-do, Korea
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  • Jin-Ho Choi,

    1. Faculty of Food Science and Biotechnology, Pukyong National University, Busan, Korea
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  • Yoo-Hun Suh

    Corresponding author
    1. 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
    2. Braintropia Company, Gyeonggi-do, Korea
    • Department of Pharmacology, College of Medicine, Seoul National University, 28 Yeongeon-dong, Jongno-gu, Seoul, 110-799, Korea
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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 peptide1–42-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 peptide1–42-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 peptide1–42, 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. © 2007 Wiley-Liss, Inc.

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