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Published on: February 27, 2016

Identification of a small molecule activator of SIRT1 gene expression

Si-Young Cho1, Miook Cho, Dae Bang Seo

  • 1R&D Center, Amorepacific Corporation, Gyeonggi-do, Korea 446-729.

Aging
|March 26, 2013
PubMed

Insights

Syringaresinol, from ginseng, activates SIRT1 gene expression by binding FOXO3 to the SIRT1 promoter. This delays cellular senescence and improves endothelial function, offering therapeutic potential for aging-related diseases.

Area of Science:

  • Molecular biology
  • Gerontology
  • Pharmacology

Background:

  • SIRT1 expression offers benefits in aging-related diseases.
  • SIRT1 activators are therapeutic targets for age-related conditions.
  • No small molecule activators of SIRT1 gene expression have been identified.

Purpose of the Study:

  • To identify a small molecule activator of SIRT1 gene expression.
  • To investigate the mechanism of SIRT1 gene activation by syringaresinol.
  • To evaluate the effects of syringaresinol-induced SIRT1 expression on endothelial cells.

Main Methods:

  • Syringaresinol isolated from Panax ginseng berry pulp.
  • Treatment of human umbilical endothelial cells (HUVECs) with syringaresinol.
  • Assessed FOXO3 binding to the SIRT1 promoter.
  • Measured SIRT1 expression, cellular senescence, and endothelial function markers.

Main Results:

  • Syringaresinol activated SIRT1 gene expression in HUVECs.
  • Syringaresinol induced sequence-specific binding of FOXO3 to the SIRT1 promoter.
  • Increased SIRT1 expression delayed cellular senescence and improved endothelial function markers.
  • These effects were dependent on FOXO3.

Conclusions:

  • Syringaresinol is a novel activator of SIRT1 gene expression.
  • Syringaresinol acts via FOXO3-mediated transcription.
  • Syringaresinol demonstrates therapeutic potential for age-related diseases and endothelial dysfunction.

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