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The Pharmacogenomics Journal (2012) 12, 372–378; doi:10.1038/tpj.2011.24; published online 7 June 2011 Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region Y Hu1, E A Ehli1,2, J J Hudziak3 and G E Davies1,2 1Avera Institute for Human Behavioral Genetics, Avera Behavioral Health Center, Sioux Falls, SD, USA 2Department of Psychiatry, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA 3Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA Correspondence: Dr GE Davies, Avera Institute for Human Behavioral Genetics, Avera Behavioral Health Center, Suite 200, Room G521, Sioux Falls, SD 57108, USA. E-mail: email@example.com Received 11 March 2011; Revised 3 May 2011; Accepted 11 May 2011 Advance online publication 7 June 2011 Top of page Abstract The aim of this study was to investigate the effect of berberine and evodiamine on serotonin transporter (5-HTT) expression and then test how allelic variations previously identified in the promoter region could modulate that effect in the serotonergic neuronal cell line RN46A. Both berberine and evodiamine, alone and in combination, increased 5-HTT mRNA and protein expression significantly across the various alleles. When tested against the S, XS11, LG, LA, XL17, and XL18 alleles, respectively, 100 μM berberine increased 5-HTT promoter activities by 67%, 128.7%, 106.9%, 100.4%, 26.2% and 82%, 2 μM evodiamine increased 5-HTT promoter activities by 216.7%, 81.6%, 305.6%, 181.5%, 175.3% and 102.2%. Berberine and evodiamine increased 5-HTT promoter activity differently depending on the genetic variation of the 5-HTTLPR polymorphism. This study has provided a convincing example of how herbal compounds influence the expression of one of the most intensively studied psychiatric candidate genes, the serotonin transporter.