16:00 - 18:00
Room: Poster Area - Poster Shed
Poster Presentation
Influence of St. John´s wort extract and its components on gene expression in neuronal cells after induction of stress
S Verjee 1, A Weston 2, Olaf Kelber 3, Christiane Kolb 4, Heba Aziz-Kalbhenn 4, Veronika Butterweck 1
1 Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Muttenz
2 Institute for Chemistry and Bioanalytics, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Muttenz
3 Innovation & Development, Consumer Health, Bayer Phytomedicines Supply and Development Center, Steigerwald Arzneimittelwerk GmbH, Darmstadt
4 Medical Affairs Phytomedicines, Innovation & Development, Consumer Health, Bayer Phytomedicines Supply and Development Center, Steigerwald Arzneimittelwerk GmbH, Darmstadt

Introduction:

It is well known that dysregulation of the HPA axis plays an important part in the development and maintenance of depressive symptoms. Glucocorticoids affect cellular and molecular events in brains by modulating the expression of many genes during stress. In the present study we evaluated the effects of a St. John’s wort extract (STWE, extraction medium ethanol 80 %, DER 3-6:1), hyperforin, miquelianin and the SSRI citalopram on the expression of genes relevant to HPA axis function in human neuronal cells.

Material and Methods:

SH-SY5Y cells were treated with STWE (20 µg/mL), hyperforin (10 µM), miquelianin (10 µM) or citalopram (10 µM) in the presence or absence of the glucocorticoid receptor agonist dexamethasone (DEX,10 μM) for 6 h and 48 h, respectively. Quantitative real time PCR was used to determine the expression of FKBP5, CREB, GRIK4, VEGF, NET, and ARRB, which have been shown to be meaningful biomarkers in the treatment response for depression. Relative expression values were determined by using the −ΔΔCt method.

Results and Discussion:

Using DEX to mimick stress conditions, we were able to show the responsiveness of the selected genes. It was shown that the gene expression pattern of FKBP5, CREB, GRIK4, VEGF, NET, and ARRB2 in SH-SY5Y neuronal cells is time and treatment dependent. Most pronounced effects were observed for FKBP5, which was upregulated after 6h (1.3 fold) but an even stronger increase in mRNA expression was observed after 48h (1.8 fold). While after 6h of co-incubation only STWE could reverse the dexamethasone induced increase in FKBP5 expression, after 48h citalopram, miquelianin and hyperforin also reversed the glucocorticoid induced increase in FKBP5 mRNA expression.

Conclusion:

The effects observed on FKBP5, CREB, GRIK4, VEGF, NET and ARRB2 are in good correlation with published data, suggesting that this in vitro model can be used to screen the responsiveness of antidepressants under stress conditions.


Reference:
Poster Session-PO-145:
Session:
Poster Presentation-1
Presenter/s:
Olaf Kelber
Presentation type:
Poster presentation
Room:
Poster Area - Poster Shed
Date:
Monday, 27th August, 2018
Time:
16:00 - 18:00
Session times:
16:00 - 18:00