Hypericum perforatum differentially affects corticosteroid receptor-mRNA expression in human monocytic U-937 cells

• Published in: Journal of psychiatric research Vol. 45; no. 9; pp. 1170 - 1177
• Main Authors: Enning, F, Murck, H, Krieg, J.-C, Vedder, H
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.09.2011; Elsevier
• Subjects: Amiloride - analogs & derivatives; Amiloride - pharmacology; Antidepressant; Antidepressant drugs; Biological and medical sciences; Cell Line, Transformed; Coccidiostats - pharmacology; Corticosteroid; Corticosteroids; Dose-Response Relationship, Drug; Dysfunction; Dysregulation; First time; Gene Expression Regulation - drug effects; Herbal; Humans; Hypericum - chemistry; Hypothalamic-pituitary-adrenal axis; Medical sciences; Monensin - pharmacology; Monocytes - drug effects; Neuroendocrine; Neuropharmacology; Pharmacology. Drug treatments; Plant Extracts - pharmacology; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Receptor; Receptors, Steroid - classification; Receptors, Steroid - genetics; Receptors, Steroid - metabolism; RNA, Messenger - metabolism; Sodium; Sodium Channel Blockers - pharmacology; Antidepressant; Dysregulation; Corticosteroid; Herbal; Receptor; Neuroendocrine; Human; Hypericum perforatum; Psychotropic; Guttiferae; Gene expression; Genetic determinism; Dicotyledones; Angiospermae; Genetics; Antidepressant agent; Spermatophyta; Biological receptor
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2011.03.007

Abstract A dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis represents a prominent finding in major depression, possibly related to a dysfunction of the corticosteroid receptor system. Antidepressants are involved in the restoration of the altered feed-back mechanism of the HPA-axis, probably via normalization of corticosteroid receptor functions. Since Hypericum perforatum has antidepressive properties, we here examined its putative actions on glucocorticosteroid receptor mRNA levels in human blood cells as a peripheral model for neuroendocrine effects in human brain cells. Our data show that Hypericum (LI 160) affects the cellular mRNA levels of both, the glucocorticoid receptor (GR)-α and its inhibitory counterpart, the GR-β, at clinically-relevant concentrations. Under these conditions, a bimodal effect was observed. Dose-response studies suggest a rather small effective concentration range and time-effect data show a primary and transient up-regulation of GR-α mRNA levels and a down-regulation of GR-β mRNA levels after 16 h of treatment. The sodium channel blocker benzamil neutralized the effects of Hypericum, pointing to an at least partial mechanism of action via this pathway. In conclusion, Hypericum treatment differentially affects GR-mRNA levels in the human system. Our data suggest a bimodal effect on GR, resulting in a time-and dose-related modification of GR-mediated cellular effects. Such a mechanism has been alleged as an important way of action for a number of antidepressants. It is the first time that a specific effect on both receptors, especially on the subtype of GR-β, is shown under antidepressive treatment in a human system under in vitro conditions.