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.
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We thank Dr Scott R Whittemore (University of Louisville, School of Medicine) for his kind provision of the RN46A raphe-derived cell line. We thank Paige S Davies for her contribution in the preparation of this manuscript.
The authors declare no conflict of interest.
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Hu, Y., Ehli, E., Hudziak, J. et al. Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region. Pharmacogenomics J 12, 372–378 (2012). https://doi.org/10.1038/tpj.2011.24