Profiling of hypothalamic and hippocampal gene expression in chronically stressed rats treated with St. John’s wort extract (STW 3-VI) and fluoxetine

Abstract

Hypericum perforatum L., known as St. John's wort (SJW), is used as a phytotherapeutic agent for the treatment of mild to moderate forms of depression. The aim of the present study was to evaluate the effect of SJW extract (STW 3-VI; 250 and 500 mg/kg; p.o.) and fluoxetine (10 mg/kg, p.o.) on genes involved in the pathogenesis of depression using a chronic restraint stress (CRS) model in rats. Of particular interest was the assessment of similarities and differences between SJW extract and fluoxetine on the gene expression level in two different brain regions. Hypothalamic and hippocampal tissues were analyzed using the Affymetrix gene chip Rat Genome 230 2.0 Array, which comprises more than 30,000 rat transcripts. Limma program and PANTHER database were used to evaluate the microarray data. Genes involved in the pathways of inflammatory processes (Mapk8), oxidative stress (Gpx3, Gstm3, Sod3) or Alzheimer's disease (Sncb, Apbb1ip) were altered by both fluoxetine and SJW extract. For all groups, several signaling pathways were identified which could provide a link between the various hypotheses of depression. In conclusion, microarray analysis proved to be a valuable tool to identify a large number of genes and resulting pathways that may serve as novel drug targets or predict drug responsiveness for SJW or fluoxetine. Based on our comprehensive analysis, it was possible to identify similarities and differences between SJW and fluoxetine which may help to better understand their molecular action and, in addition, help to find novel treatment strategies for stress-related depression.