Microarray Analysis as a Tool to Elucidate the Mechanism of Action of St. John's Wort

Hypericum perforatum L., known as St. John's wort (SJW) is indicated as phytotherapeutic agent for the treatment of mild to moderate forms of depression. Data from literature support the hypothesis that chronic stress is a major risk factor for psychiatric illnesses. The aim of the present study was to evaluate the effect of SJW extract (STW3-VI; 250 and 500mg/kg; p.o.) and fluoxetine (10mg/kg, p.o.) on genes involved in the pathogenesis of depression using a chronic restraint stress (CRS) model in rats. 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 analysis and PANTHER database were used to evaluate the microarray data. Treatment with SJW extract in both concentrations and fluoxetine reversed expression levels of several genes changed by CRS. Genes involved in pathways of inflammatory processes (Mapk8) oxidative stress (Gpx3, Gstm3, Sod3) or Alzheimer's disease (Sncb, Apbb1ip) were altered by both, fluoxetine and SJW. In all groups several pathways were identified which provide a link between the various hypotheses of depression. Gene expression results for both brain regions were verified using quantitative rPCR. In conclusion, Microarray analysis prooved 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. Based on our results it was possible to identify new candidate pathways that help to understand molecular principles of depression and in addition help to find novel treatment strategies for neuropsychiatric disorders.