Inhibitory effects of Citrus polymethoxyflavones, nobiletin and its analogues, on acetylcholinesterase activity

Junko Kimura, Kiyomitsu Nemoto, Satomi Onoue, Tohru Yamakuni, Akihito Yokosuka, Yoshihiro Mimaki, Shizuo Yamada, Masakuni Degawa, Yasushi Ohizumi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


We have previously demonstrated that nobiletin from the peels of Citrus depressa has the potential to improve cognitive dysfunction in Alzheimer's disease. In the present study, considering a choline theory for the development of Alzheimer's disease, inhibitory effects of 6 citrus polymethoxyflavones, such as nobiletin, 5-demethylnobiletin, 6-demethoxynobiletin, 3'-demethoxynobiletin, 8-demethoxynobiletin and 6,3'-di(demethoxy)nobiletin, on the activity of human acetylcholinesterase (AChE) were assessed in vitro, and the structure-activity relationships were examined. Human AChE activities in the presence and absence of each chemical were spectrophotometrically measured according to the modified Ellman's method with acetylcholine iodide as a substrate of AChE, and their inhibitory effects were assessed. Nobiletin, 8-demethoxynobiletin, and 6-demethoxynobiletin, but not the 3 other chemicals, showed definitely inhibitory effects on AChE activity, and their inhibitory activities (60∼76 % of control at 100 μM of each compound) were almost the same. Methoxyl substituents at both the 5 and 3' positions of the nobiletins were demonstrated to be essential for showing the inhibitory effect on AChE activity.

Original languageEnglish
Pages (from-to)23-26
Number of pages4
Issue number1-2
Publication statusPublished - 2011


  • Acetylcholinesterase
  • Alzheimer's disease
  • Nobiletin
  • Polymethoxyflavone

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)


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