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Hypericum perforatum differentially affects corticosteroid receptor-mRNA expression in human monocytic U-937 cells
1Department of Psychiatry and Psychotherapy, Philipps-University of Marburg, Rudolf-Bultmann-Str. 8, D-35033 Marburg, Germany.
Journal of Psychiatric Research
|May 17, 2011
Summary
Hypericum perforatum, an antidepressant, alters glucocorticoid receptor (GR)-α and GR-β mRNA levels in human cells. This bimodal effect, particularly on GR-β, may explain its antidepressant action.
Area of Science:
- Neuroendocrinology
- Pharmacology
- Molecular Biology
Background:
- Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis is common in major depression, linked to corticosteroid receptor dysfunction.
- Antidepressants may restore HPA axis feedback by normalizing corticosteroid receptor function.
Purpose of the Study:
- To investigate the effects of Hypericum perforatum (St. John's Wort) on glucocorticoid receptor (GR) mRNA levels in human blood cells.
- To explore Hypericum's potential as a peripheral model for neuroendocrine effects relevant to depression treatment.
Main Methods:
- Treatment of human blood cells with Hypericum extract (LI 160) at clinically relevant concentrations.
- Analysis of glucocorticoid receptor alpha (GR-α) and beta (GR-β) mRNA levels.
- Dose-response and time-effect studies.
- Investigation of the role of sodium channel blockers (benzamil).
Main Results:
- Hypericum significantly affected GR-α and GR-β mRNA levels in a bimodal manner.
- A narrow effective concentration range was identified.
- Treatment led to transient GR-α mRNA up-regulation and GR-β mRNA down-regulation after 16 hours.
- Benzamil partially neutralized Hypericum's effects, suggesting involvement of sodium channels.
Conclusions:
- Hypericum differentially affects GR-mRNA levels in human cells.
- The observed bimodal, time- and dose-dependent modification of GR-mRNA suggests a novel mechanism for antidepressant action.
- This study provides the first in vitro evidence of specific effects on both GR-α and GR-β subtypes under antidepressant treatment in a human system.
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