In vitro receptor screening of pure constituents of St. John's wort reveals novel interactions with a number of GPCRs.
BACKGROUND
Hypericum perforatum L. (St. John's wort; SJW) is one of the leading psychotherapeutic phytomedicines and great effort has been devoted to clarifying its mechanism of action.


OBJECTIVE
We have undertaken a comprehensive analysis of several pure compounds isolated from the crude extract to gain further insight into the molecular actions of various substituents of SJW.


METHODS
We characterized the in vitro pharmacology of the naphthodianthrones hypericin and pseudohypericin, the phloroglucinol derivative hyperforin, and several flavonoids at 42 biogenic amine receptors and transporters using the resources of the National Institute of Mental Health Psychoactive Drug Screening Program.


RESULTS
The biflavonoid amentoflavone significantly inhibited binding at serotonin (5-HT(1D), 5-HT(2C)), D(3)-dopamine, delta-opiate, and benzodiazepine receptors. The naphthodianthrone hypericin had significant activity at D(3)- and D(4)-dopamine receptors and beta-adrenergic receptors. With the exception of the D(1)-dopamine receptor, the phloroglucinol derivative hyperforin was less active than other SJW constituents tested on all screened receptors.


CONCLUSIONS
Our present in vitro data clearly show that several pure substances in SJW are potential CNS psychoactive agents and may contribute to the antidepressant efficacy of the plant in a complex manner. Our data also reveal novel and heretofore unexpected interactions of pure compounds in SJW at a number of GPCRs, transporters, and ion channels. We hypothesize that additive or synergistic actions of different single compounds may be responsible for the antidepressant efficacy of SJW. These results and this general approach may impact our understanding of phytomedicines in general and H. perforatum specifically.
Institute of Pharmacology and Toxicology, Westfälische Wilhelms-Universität Muenster, Domagkstrasse 12, 48149 Muenster, Germany. butterv@uni-muenster.de
Veronika
V
Butterweck
Adolf
A
Nahrstedt
Jon
J
Evans
Sandy
S
Hufeisen
Laura
L
Rauser
Jason
J
Savage
Beth
B
Popadak
Paul
P
Ernsberger
Bryan L
BL
Roth
D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D001679:Biogenic Amines / Q000378:metabolism; D001692:Biological Transport; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry; D011869:Radioligand Assay; D017982:Receptors, Biogenic Amine / Q000187:drug effects* / Q000378:metabolism
D000928:Antidepressive Agents; D001679:Biogenic Amines; D005419:Flavonoids; D026901:Membrane Transport Proteins; D010936:Plant Extracts; D017982:Receptors, Biogenic Amine; D019204:GTP-Binding Proteins