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Hypericum perforatum L. extract does not inhibit 5-HT transporter in rat brain cortex
M Gobbi1, F D Valle, C Ciapparelli
1Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. Gobbi@irfmn.mnegri.it
Naunyn-Schmiedeberg'S Archives of Pharmacology
|October 30, 1999
Summary
Hypericum perforatum extract shows antidepressant effects by releasing serotonin (5-HT) from vesicles, not by inhibiting its reuptake. This reserpine-like action may not fully explain its antidepressant properties, suggesting other unknown mechanisms are involved.
Area of Science:
- Pharmacology
- Neuroscience
- Phytochemistry
Background:
- Hypericum perforatum L. (St. John's Wort) is a recognized antidepressant.
- Its precise mechanism of action remains unclear, though it's known to affect neurotransmitter uptake.
- Previous studies suggest inhibition of serotonin (5-HT), dopamine, and noradrenaline uptake.
Purpose of the Study:
- To investigate the in vitro mechanism of action of a hydromethanolic H. perforatum extract on serotonin.
- To determine if the extract acts as a classical serotonin reuptake inhibitor or exhibits other properties.
- To explore potential interactions with GABA, benzodiazepine, and 5-HT1 receptors.
Main Methods:
- Inhibition of [3H]5-HT accumulation in rat brain cortical synaptosomes.
- Assessment of [3H]citalopram binding to serotonin transporters.
- Measurement of tritium release from synaptosomes loaded with [3H]5-HT.
- Receptor binding studies for GABA, benzodiazepine, and 5-HT1 receptors.
- Analysis of rat brain 5-HT and 5-hydroxyindoleacetic acid levels after oral administration.
Main Results:
- The H. perforatum extract inhibited [3H]5-HT accumulation (IC50 = 7.9 microg/ml), but not via direct blockade of serotonin transporters.
- Both the extract and pure hyperforin induced 5-HT release from synaptosomes, resembling reserpine-like activity.
- In vivo studies showed no significant changes in brain 5-HT levels after effective antidepressant doses.
- No significant interaction was observed with GABA, benzodiazepine, and 5-HT1 receptors.
Conclusions:
- The hydromethanolic H. perforatum extract exhibits reserpine-like properties, causing 5-HT release rather than classical reuptake inhibition.
- The in vitro reserpine-like effect concentrations may not be achieved in vivo at pharmacologically relevant doses.
- The antidepressant effects of H. perforatum are likely mediated by mechanisms other than direct 5-HT reuptake inhibition or interaction with tested receptors.