In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract

Area of Science:

• Pharmacology
• Phytochemistry
• Herbal Medicine

Background:

• Hypericum perforatum (St. John's wort) has a long history of medicinal use, particularly for depression.
• Hypericin, a red pigment, has been traditionally considered the primary active compound.
• Modern research questions hypericin's sole contribution to the plant's therapeutic effects.

Purpose of the Study:

• To investigate the in vitro pharmacological activity of Hypericum perforatum extract and pure hypericin.
• To compare the receptor binding profiles of the crude extract versus isolated hypericin.
• To explore alternative mechanisms for Hypericum's psychotherapeutic effects, focusing on GABA receptor interactions.

Main Methods:

• A crude Hypericum perforatum extract underwent 39 in vitro receptor assays and 2 enzyme assays.
• Pure hypericin was also subjected to the same in vitro receptor and enzyme assays.
• Pharmacokinetic considerations regarding achievable concentrations in vivo were evaluated.

Main Results:

• Pure hypericin demonstrated affinity only for NMDA receptors.
• The crude extract exhibited significant affinity for adenosine, GABAA, GABAB, benzodiazepine, inositol triphosphate, and monoamine oxidase (MAO) A and B receptors.
• Achievable concentrations in vivo suggest that receptor affinities, except for GABAA and GABAB, may not be relevant for oral administration.

Conclusions:

• The broad receptor binding profile of the crude extract suggests constituents other than hypericin are crucial for Hypericum's effects.
• GABA receptor binding is highlighted as a potentially important pharmacologic mechanism for Hypericum's antidepressant activity.
• Further research into alternative pharmacologic mechanisms is warranted to fully understand Hypericum perforatum's therapeutic potential.