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Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits

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Abstract

Cholinesterase (ChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors are promising agents for the treatment of Alzheimer’s disease (AD). In the present study, we examined the inhibitory activity of seven compounds isolated from the fruits of Cornus officinalis, cornuside, polymeric proanthocyanidins, 1,2,3-tri-O-galloyl-β-d-glucose, 1,2,3,6-tetra-O-galloyl-β-d-glucose, tellimagrandin I, tellimagrandin II, and isoterchebin, against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1. All of the compounds displayed concentration-dependent in vitro inhibitory activity toward the ChEs and BACE1. Among them, tellimagrandin II exhibited the best inhibitory activity toward ChEs, whereas the best BACE1 inhibitor was 1,2,3,6-tetra-O-galloyl-β-d-glucose. Isoterchebin and polymeric proanthocyanidins were also significant ChE inhibitors. The kinetic and docking studies demonstrated that all compounds interacted with both the catalytic active sites and the peripheral anionic sites of the ChEs and BACE1. Tellimagrandin II, isoterchebin, and the polymeric proanthocyanidins exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. In conclusion, we identified significant ChE and BACE1 inhibitors from Corni Fructus that could have value as new multi-targeted compounds for anti-AD agents.

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Authors and Affiliations

  1. Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea

    Himanshu Kumar Bhakta & Jae Sue Choi

  2. Department of Medicinal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, 369-873, Republic of Korea

    Chan Hum Park

  3. Graduate School of Science and Engineering for Research, University of Toyama, Toyama, 930-8555, Japan

    Takako Yokozawa

  4. Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan

    Takashi Tanaka

  5. Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea

    Hyun Ah Jung

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  1. Himanshu Kumar Bhakta
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  2. Chan Hum Park
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  3. Takako Yokozawa
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  4. Takashi Tanaka
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Correspondence to Hyun Ah Jung or Jae Sue Choi.

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Bhakta, H.K., Park, C.H., Yokozawa, T. et al. Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits. Arch. Pharm. Res. 40, 836–853 (2017). https://doi.org/10.1007/s12272-017-0924-z

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  • DOI: https://doi.org/10.1007/s12272-017-0924-z

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