title: Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in mice.
abstract: The pharmacological effects of extracts of Hypericum perforatum (St John's wort) were characterized in-vitro and ex-vivo, in relation to its behavioural effects. In in-vitro experiments, St John's wort inhibited brain synaptosomal [(3)H]serotonin uptake in mice with little effect on specific [(3)H]paroxetine binding. For selective serotonin-reuptake inhibitors (SSRIs), the IC50 value for [(3)H]serotonin uptake (molar concentration of unlabelled drug necessary to displace 50% of specific uptake) correlated well with the inhibition constant K(i) value for [(3)H]paroxetine binding in mouse brain. Oral administration of St John's wort (900 mg kg(-1)), paroxetine (1 mg kg(-1)) and sertraline (10 mg kg(-1)) brought about significant increases in the K(m) value for [(3)H]serotonin uptake into brain synaptosomes 4 h later, and only SSRIs suppressed specific [(3)H]paroxetine binding in mouse brain. St John's wort and SSRIs significantly inhibited marble-burying behaviour in mice and the time-course of attenuation of this behaviour by St John's wort was similar to that of [(3)H]serotonin uptake inhibition. In the forced swimming test, St John's wort, but not SSRIs, suppressed the immobility time of mice after oral administration. These results provide the first in-vivo evidence to suggest that the mode of antidepressant action of St John's wort differs from that of SSRIs. Thus, this study may have a significant impact on phytotherapy with St John's wort.
authors.affiliation: Department of Biopharmaceutical Sciences and COE Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Hirano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchida
authors.forename: Yumi
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Jun
authors.initials: J
authors.lastname: Yamada
authors.forename: Keizo
authors.initials: K
authors.lastname: Umegaki
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020902:Hypericum; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010936:Plant Extracts; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin