Dehydroevodiamine•HCl protects against memory impairment and cerebral amyloid-β production in Tg2576 mice by acting as a β-secretase inhibitor

Ki Young Shin, Su Jin Noh, Cheol Hyoung Park, Yun Ha Jeong, Keun A. Chang, Jakyung Yoo, Hee Jin Kim, Sungji Ha, Hye Sun Kim, Hyun Ju Park, Jun Ho Lee, Cheil Moon, Yoo Hun Suh

Research output: Contribution to journalArticle

Abstract

We previously demonstrated that dehydroevodiamine•HCl (DHED), which was purified from Evodia rutaecarpa Bentham (Rutaceae), has beneficial effects on memory impairment and neuronal damage in three disease models. To investigate the preventive action of DHED in Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by memory decline, amyloid-β (Aβ) protein-containing neuritic plaques and neurofibrillary tangles, in this study, we proposed that DHED may be therapeutically effective against the memory impairment and disease-related neurochemical changes that occur in Tg2576 (Tg) mice. DHED (0.5 mg/kg) was intraperitoneally administered to 7-month-old Tg and wild type mice for 4 months. In passive avoidance and water maze tests, DHED improved memory impairment of Tg mice after 4 months of administration. DHED also reduced cortical levels of soluble Aβ40, soluble Aβ42 and total Aβ peptides in the Tg mice. Additionally, we investigated whether DHED may be a β-secretase inhibitor that affects the production of Aβ related to the formation of neuritic plaques. DHED directly inhibited β-secretase activity in a concentrationdependent manner. The concentration required for 50 % enzyme inhibition (IC50) was 40.96 µM, and DHED may act as a competitive inhibitor of β-secretase. Moreover, DHED interacted strongly with BACE1 (β-secretase 2QP8), as demonstrated in the analysis of the binding mode of DHED in the active site of human BACE1. In conclusion, DHED may exhibit therapeutic effects for AD as a β-secretase inhibitor.

Original languageEnglish (US)
Pages (from-to)935-944
Number of pages10
JournalCNS and Neurological Disorders - Drug Targets
Volume15
Issue number8
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Fingerprint

Amyloid Precursor Protein Secretases
Amyloid
Amyloid Plaques
Alzheimer Disease
Evodia
Serum Amyloid A Protein
Neurofibrillary Tangles
Therapeutic Uses
Neurodegenerative Diseases
Inhibitory Concentration 50
Catalytic Domain
Peptides
Water
Enzymes

Keywords

  • Alzheimer’s disease
  • Dehydroevodiamine•HCl
  • Inhibitor
  • Memory
  • β-secretase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Cite this

Dehydroevodiamine•HCl protects against memory impairment and cerebral amyloid-β production in Tg2576 mice by acting as a β-secretase inhibitor. / Shin, Ki Young; Noh, Su Jin; Park, Cheol Hyoung; Jeong, Yun Ha; Chang, Keun A.; Yoo, Jakyung; Kim, Hee Jin; Ha, Sungji; Kim, Hye Sun; Park, Hyun Ju; Lee, Jun Ho; Moon, Cheil; Suh, Yoo Hun.

In: CNS and Neurological Disorders - Drug Targets, Vol. 15, No. 8, 01.10.2016, p. 935-944.

Research output: Contribution to journalArticle

Shin, KY, Noh, SJ, Park, CH, Jeong, YH, Chang, KA, Yoo, J, Kim, HJ, Ha, S, Kim, HS, Park, HJ, Lee, JH, Moon, C & Suh, YH 2016, 'Dehydroevodiamine•HCl protects against memory impairment and cerebral amyloid-β production in Tg2576 mice by acting as a β-secretase inhibitor', CNS and Neurological Disorders - Drug Targets, vol. 15, no. 8, pp. 935-944. https://doi.org/10.2174/1871527315666160815163723
Shin, Ki Young ; Noh, Su Jin ; Park, Cheol Hyoung ; Jeong, Yun Ha ; Chang, Keun A. ; Yoo, Jakyung ; Kim, Hee Jin ; Ha, Sungji ; Kim, Hye Sun ; Park, Hyun Ju ; Lee, Jun Ho ; Moon, Cheil ; Suh, Yoo Hun. / Dehydroevodiamine•HCl protects against memory impairment and cerebral amyloid-β production in Tg2576 mice by acting as a β-secretase inhibitor. In: CNS and Neurological Disorders - Drug Targets. 2016 ; Vol. 15, No. 8. pp. 935-944.
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AU - Noh, Su Jin

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AU - Jeong, Yun Ha

AU - Chang, Keun A.

AU - Yoo, Jakyung

AU - Kim, Hee Jin

AU - Ha, Sungji

AU - Kim, Hye Sun

AU - Park, Hyun Ju

AU - Lee, Jun Ho

AU - Moon, Cheil

AU - Suh, Yoo Hun

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