title: Identification of a small molecule activator of SIRT1 gene expression.
abstract: Increased SIRT1 expression exerts beneficial effects in transgenic animal models, ameliorating the onset and progression of aging-related disease phenotypes in various organs including the heart. The potential beneficial effects of SIRT1 have made SIRT1 a prime therapeutic target for age-related diseases and considerable efforts led to the identification of small molecule activator of SIRT1 protein. Thus far, however, a small molecule activator of SIRT1 gene expression has not been reported. Here, we report that syringaresinol, isolated from Panax ginseng berry pulp, is an activator of SIRT1 gene expression. Using human umbilical endothelial cells (HUVECs), we show that syringaresinol treatment induced binding of FOXO3 to the SIRT1 promoter in a sequence-specific manner, leading to induction of SIRT1 expression. Increased SIRT1 expression in HUVECs by syringaresinol treatment delayed cellular senescence and improved various markers of endothelial functions in a FOXO3 dependent manner. Collectively, these findings bring to light a new transcription activator of SIRT1 that may have therapeutic potential.
authors.affiliation: R&D Center, Amorepacific Corporation, Gyeonggi-do, Korea 446-729.
authors.forename: Si-Young
authors.initials: SY
authors.lastname: Cho
authors.forename: Miook
authors.initials: M
authors.lastname: Cho
authors.forename: Dae Bang
authors.initials: DB
authors.lastname: Seo
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Yousin
authors.initials: Y
authors.lastname: Suh
mesh_terms: D002478:Cells, Cultured; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D005663:Furans; D017705:Lignans; C042192:syringaresinol; C447939:SIRT1 protein, human; D056564:Sirtuin 1