title: Extracts of St. John's wort and various constituents affect beta-adrenergic binding in rat frontal cortex.
abstract: The present study was designed to get further insight into the mode of antidepressant action of extracts prepared from St. John's wort (SJW) and relevant active constituents. Down-regulation of central beta-adrenergic receptors (beta-AR's) has been widely considered a common biochemical marker of antidepressant efficacy. Although previous studies have reported a beta-AR down-regulation for SJW extracts, in vivo studies that compare the effects of SJW extracts with those of relevant active constituents on beta-AR density have not been done yet. We used quantitative radioligand receptor-binding-studies to examine in rats the effects of short-term (2 wks) and long-term (8 wks) administration of different SJW extracts and constituents on beta-AR binding in rat frontal cortex. The effects were compared to those of the standard antidepressants imipramine and fluoxetine. [125I]CYP binding to beta-AR was found to be decreased after short as well as after long-term treatment with imipramine (36%, 40%). Short-term treatment with fluoxetine decreased the number of beta-adrenergic receptors (17%) while long-term treatment with fluoxetine elicited an increase (14%) in beta-AR-binding. This effect was comparable to that of the lipophilic CO2 extract which decreased beta-AR-binding (13%) after two weeks and slightly increased the number of beta-AR's after 8 weeks (9%). Short-term treatment with the methanolic SJW extract decreased beta-AR-binding (14%), no effects for this extract were observed after 8 weeks. Treatment with hypericin led to a significant down-regulation (13%) of beta-AR's in the frontal cortex after 8-weeks, but not after 2 weeks, while hyperforin (used as trimethoxybenzoate, TMB), and hyperoside were ineffective in both treatment paradigms. Compared to the SJW extracts and single compounds the effect of imipramine on beta-AR-binding was more pronounced in both treatment paradigms.
authors.affiliation: Institute of Pharmacology and Toxicology, Universitätsklinikum Münster, Domagkstrasse 12, 48149 Münster, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Simbrey
authors.forename: H
authors.initials: H
authors.lastname: Winterhoff
authors.forename: V
authors.initials: V
authors.lastname: Butterweck
mesh_terms: D000818:Animals; D000873:Anthracenes; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D020902:Hypericum; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010696:Phloroglucinol / Q000031:analogs & derivatives; D010936:Plant Extracts / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology
chemical_list: D000873:Anthracenes; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D001643:Bridged Bicyclo Compounds; D010936:Plant Extracts; D011943:Receptors, Adrenergic, beta; D013729:Terpenes; D005473:Fluoxetine; D010569:Perylene; C004965:hypericin; C021304:hyperoside; D011794:Quercetin; D010696:Phloroglucinol; D007099:Imipramine; C001654:hyperforin