Extracts and Constituents ofHypericum PerforatumInhibit the Binding of Various Ligands to Recombinant Receptors Expressed with the Semliki Forest Virus System

Abstract

Extracts, fractions and constituents of Hypericum perforatum were studied for in vitro receptor binding with various ligands to recombinant CNS receptors expressed with the Semliki Forest virus expression system. For this purpose we have prepared membranes of CHO cells with high density of several opioid, serotonin, estrogen, histamine, GABAA, neurokinin and metabotropic glutamate receptors, respectively. A lipophilic Hypericum fraction revealed relatively potent inhibition to the binding of the mu-, delta- and kappa-opioid and the 5-HT6 and 5-HT7 receptors. Moreover, Hypericum constituents such as the naphthodianthrones, hypericin and pseudohypericin, and the phloroglucinole hyperforin inhibited both binding to the opioid and serotonin receptors in the lower micromolar range. Estrogen binding was 50% inhibited by the biflavonoid I3,II8-biapigenin at micromolar concentration. The lipophilic Hypericum fraction provided a less potent inhibition of the neurokinin-1 receptor binding compared to the opioid and serotonin receptors. A total ethanolic Hypericum extract potently inhibited GABAA binding at approximately 3 micrograms/ml. This inhibition is however not specific to Hypericum, since extracts of plants like Valeriana officinalis and Passiflora incarnata showed similar inhibitions. Binding to neither histamine nor metabotropic glutamate receptors was affected by Hypericum extracts. These results support the hypothesis that several active constituents of Hypericum might in a synergistic way contribute to its antidepressant effect in the central nervous system.

Hyperforin-Containing Extracts of St John's Wort Fail to Alter Gene Transcription in Brain Areas Involved in HPA Axis Control in a Long-Term Treatment Regimen in Rats

“…The phloroglucinol derivative hyperforin has recently become a molecule of increasing interest. Studies have demonstrated significant effects of hyperforin on various serotonergic, noradrenergic, dopaminergic, cholinergic, and opioid system activities in vitro (Chatterjee et al, 1998a;Holcomb et al, 1982;Müller et al, 1998Müller et al, , 2001Neary et al, 2001;Simmen et al, 1999;Singer et al, 1999;Wonnemann et al, 2001). As the in vitro data have been used to argue that hyperforin is the major active principle of SJW extract, we determined in the present study whether it is active in vivo in a model of therapeutic efficacy.…”

“…The pharmacological activity of SJW extracts has recently been reviewed (Butterweck, 2003;Greeson et al, 2001;Nathan, 1999). Reports about the antidepressant activity of SJW extracts and their constituents both in vivo and in vitro have been published (Baureithel et al, 1997;Butterweck et al, 1997Butterweck et al, , 1998Butterweck et al, , 2000Butterweck et al, , 2001aButterweck et al, , b, 2002Calapai et al, 1999;Chatterjee et al, 1996Chatterjee et al, , 1998aDi Matteo et al, 2000;Franklin and Cowen, 2001;Gobbi et al, 1999Gobbi et al, , 2001Müller et al, 1997Müller et al, , 1998Müller et al, , 2001Simmen et al, 1999Simmen et al, , 2001Singer et al, 1999;Wonnemann et al, 2001).…”

“…However, besides hypericin, pharmacological research on SJW has focused on either lipophilic extracts obtained with hypercritical CO 2 that were devoid of hypericins and flavonoids, but enriched with hyperforin (Bhattacharya et al, 1998;Chatterjee et al, 1998b;Dimpfel et al, 1998;Franklin and Cowen, 2001;Gobbi et al, 2001;Simmen et al, 1999), or hydroalcoholic extracts that were standardized on a certain amount of hyperforin (Chatterjee et al, 1996(Chatterjee et al, , 1998bDimpfel et al, 1998;Franklin and Cowen, 2001;Gobbi et al, 2001;Simmen et al, 1999Simmen et al, , 2001Wonnemann et al, 2001). The phloroglucinol derivative hyperforin has recently become a molecule of increasing interest.…”

“…The effects were compared to those of the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Fluoxetine was chosen as a reference control because it was shown in several studies that similar to the SSRI, hyperforin inhibited serotonin reuptake in in vitro experiments (Chatterjee et al, 1998a;Gobbi et al, 1999;Jensen et al, 2001;Müller et al, 1998;Neary et al, 2001;Simmen et al, 1999;Wonnemann et al, 2001).…”

Flavonoids as Opioid Receptor Ligands: Identification and Preliminary Structure−Activity Relationships

“…Test compounds were first assayed at 10 μM for intrinsic activity (agonist or inverse agonist) using the [ 35 4) at room temperature for 1 h, after which bound radioligand was separated from free via rapid vacuum filtration over GF-B filters with a Brandel Scientific (Gaithersburg, MD) 96-well harvester. Bound radioactivity was determined using a TopCount 12-detector instrument (Packard Instruments) using standard scintillation counting techniques.…”