Interactions between neurotransmitter receptors involved in the pathophysiology of
depression, anxiety and ethanol consumption and two extracts (hydromethanolic and
lipophilic extracts obtained with hypercritical CO2 ) from Hypericum Perforatum L or St. John's wort (SJW) and three constituents (hyperforin, hypericin and biapigenin)
were evaluated by in vitro binding assays. The two extracts, tested at 10 µg/ml, did not inhibit ligand binding
at the following receptors: serotonin 5-HT6 and 5-HT7 , benzodiazepine, sigma and neuropeptide Y (NPY) Y1 and Y2 receptors. The hydromethanolic extract, but not the lipophilic extract, interacted
with GABAA receptors (IC50 5.5 µg/ml), while both interacted with the dopamine (DA) transporters, albeit with
high IC50 values (24.5 and 12.9 µg/ml, respectively). Biapigenin (1 µg/ml, 2 µM) inhibited
ligand binding at benzodiazepine receptors only (IC50 : 2 µM). Hyperforin (1 µg/ml, 2 µM) only inhibited [3 H]WIN-35,428 binding to DA transporters, although the IC50 (5 µM) was higher than the IC50 found for inhibition of the synaptosomal DA reuptake (0.8 µM). This finding extended
the same observation previously described for the 5-HTergic system to the DAergic
system, confirming that the inhibition of monoamine reuptake is due to a different
mechanism than that of synthetic antidepressants. Hypericin showed micromolar affinities
for both NPY-Y1 and Y2 receptors and for sigma receptors (IC50 3 - 4 µM). These hypericin activities might be of interest because NPY and sigma
receptors have been associated with anxiety disorders, depressive illnesses and ethanol
consumption. However, they were present at relatively high hypericin concentrations,
and were also light-dependent (i. e. the IC50 values increased when binding assays were carried out in the dark). Thus, our in vitro binding results may suggest that either the pharmacological effects of SJW are due
to other molecules than hypericin or hyperforin (other constituents or active metabolites),
or that the mechanism of action is different from those that have been considered
up to now.
References
in vitro by amentoflavone, a constituent of various species of Hypericum.
Pharm Acta Helv.
1997;
72
153-157
125 I][Leu31 ,Pro34 ]peptide YY and [125 I]peptide YY3-36 as selective Y1 and Y2 radioligands.
J Pharmacol Exp Ther.
1995;
272
673-680
6 serotonin receptor.
J Neurochem.
1996;
66
47-56
A and GABAB receptor subtypes on serotonergic neurons.
Brain Res.
1986;
371
372-375
+1 .
J Pharmacol Exp Ther.
1999;
290
1363-1368
7 receptor binding sites in rat hypothalamus: sensitivity to chronic antidepressant
treatment.
Mol Pharmacol.
1995;
47
99-103
