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Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities

Hiroyuki Nagase1, Naoki Omae, Akiko Omori

  • 1Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.

Biochemical and Biophysical Research Communications
|October 29, 2005
PubMed

Insights

Nobiletin, a citrus flavonoid, enhances cAMP response element (CRE) transcription and promotes neurite outgrowth, offering potential for treating neurodegenerative disorders by improving memory function.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Dysregulated cAMP response element (CRE) transcription is implicated in central nervous system (CNS) neurodegenerative disorders.
  • Natural compounds are being investigated for neuroprotective properties against CNS diseases.

Purpose of the Study:

  • To evaluate the effects of six citrus flavonoids on CRE-dependent transcription and neurite outgrowth in PC12D cells.
  • To identify potential natural compounds for treating neurodegenerative disorders.

Main Methods:

  • Screened six citrus flavonoids (nobiletin, 5-demethylnobiletin, tangeretin, sinensetin, 6-demethoxytangeretin, 6-demethoxynobiletin) for CRE-dependent transcription.
  • Assessed neurite outgrowth induction in PC12D cells.
  • Investigated the role of ERK/MAP kinase signaling and CREB phosphorylation.
  • Administered nobiletin orally to olfactory-bulbectomized mice to assess memory function.

Main Results:

  • Nobiletin demonstrated the most potent enhancement of CRE-dependent transcription and neurite outgrowth.
  • Nobiletin's effects were concentration-dependent and correlated with increased CREB phosphorylation via ERK/MAP kinase signaling.
  • Oral administration of nobiletin improved impaired memory in mice with cholinergic neurodegeneration.

Conclusions:

  • Nobiletin effectively stimulates CRE-dependent transcription and neurite outgrowth, suggesting a neuroprotective mechanism.
  • Nobiletin's ability to rescue impaired memory indicates its potential as a lead compound for neurodegenerative disease drug development.

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