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Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in mice.
J Pharm Pharmacol 2004; 56(12):1589-95JP

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+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15563766

Citation

Hirano, Kazufumi, et al. "Effects of Oral Administration of Extracts of Hypericum Perforatum (St John's Wort) On Brain Serotonin Transporter, Serotonin Uptake and Behaviour in Mice." The Journal of Pharmacy and Pharmacology, vol. 56, no. 12, 2004, pp. 1589-95.
Hirano K, Kato Y, Uchida S, et al. Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in mice. J Pharm Pharmacol. 2004;56(12):1589-95.
Hirano, K., Kato, Y., Uchida, S., Sugimoto, Y., Yamada, J., Umegaki, K., & Yamada, S. (2004). Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in mice. The Journal of Pharmacy and Pharmacology, 56(12), pp. 1589-95.
Hirano K, et al. Effects of Oral Administration of Extracts of Hypericum Perforatum (St John's Wort) On Brain Serotonin Transporter, Serotonin Uptake and Behaviour in Mice. J Pharm Pharmacol. 2004;56(12):1589-95. PubMed PMID: 15563766.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in mice. AU - Hirano,Kazufumi, AU - Kato,Yasuhiro, AU - Uchida,Shinya, AU - Sugimoto,Yumi, AU - Yamada,Jun, AU - Umegaki,Keizo, AU - Yamada,Shizuo, PY - 2004/11/27/pubmed PY - 2005/3/2/medline PY - 2004/11/27/entrez SP - 1589 EP - 95 JF - The Journal of pharmacy and pharmacology JO - J. Pharm. Pharmacol. VL - 56 IS - 12 N2 - 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. SN - 0022-3573 UR - https://www.unboundmedicine.com/medline/citation/15563766/Effects_of_oral_administration_of_extracts_of_Hypericum_perforatum__St_John's_wort__on_brain_serotonin_transporter_serotonin_uptake_and_behaviour_in_mice_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3573&date=2004&volume=56&issue=12&spage=1589 DB - PRIME DP - Unbound Medicine ER -