Psychopharmacology

, Volume 162, Issue 2, pp 193–202

In vitro receptor screening of pure constituents of St. John's wort reveals novel interactions with a number of GPCRs

  • Veronika Butterweck
  • Adolf Nahrstedt
  • Jon Evans
  • Sandy Hufeisen
  • Laura Rauser
  • Jason Savage
  • Beth Popadak
  • Paul Ernsberger
  • Bryan L. Roth
Original Investigation

DOI: 10.1007/s00213-002-1073-7

Cite this article as:
Butterweck, V., Nahrstedt, A., Evans, J. et al. Psychopharmacology (2002) 162: 193. doi:10.1007/s00213-002-1073-7

Heading

Abstract

Rationale.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-HT1D, 5-HT2C), D3-dopamine, δ-opiate, and benzodiazepine receptors. The naphthodianthrone hypericin had significant activity at D3- and D4-dopamine receptors and β-adrenergic receptors. With the exception of the D1-dopamine receptor, the phloroglucinol derivative hyperforin was less active than other SJW constituents tested on all screened receptors.

Conclusion. 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.

St. John's wort Hypericum perforatum Hyperforin Hypericin Flavonoids Receptor screening

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Veronika Butterweck
    • 1
  • Adolf Nahrstedt
    • 3
  • Jon Evans
    • 2
  • Sandy Hufeisen
    • 2
  • Laura Rauser
    • 2
  • Jason Savage
    • 2
  • Beth Popadak
    • 2
  • Paul Ernsberger
    • 2
  • Bryan L. Roth
    • 2
  1. 1.Institute of Pharmacology and Toxicology, Westfälische Wilhelms-Universität Muenster, Domagkstrasse 12, 48149 Muenster, GermanyGermany
  2. 2.NIMH Psychoactive Drug Screening Program, Departments of Biochemistry, Psychiatry, and Neurosciences, Case Western Reserve University Medical School, Cleveland, Ohio, USAUSA
  3. 3.Institute of Pharmaceutical Biology and Phytochemistry, Westfälische Wilhelms-Universität, Muenster, GermanyGermany
  4. 4.Departments of Nutrition and Biochemistry, Case Western Reserve University Medical School, Cleveland, OH 44106, USAUSA