Activity Profiles of Two Hyperforin-Containing Hypericum Extracts in Behavioral Models

Abstract

The behavioral activity profile of a therapeutically used alcoholic hypericum extract containing hyperforin (4.5%) in rodent models was compared with that of an experimental CO2 extract devoid of hypericines but highly enriched in hyperforin (38.8%). The antidepressant activities of 50, 150 and 300 mg/ kg/day of the alcoholic extract were similar to those of 5, 15 and 30 mg/kg/day respectively of the CO2 extract. The ethanol extract in the same dose range potentiated dopaminergic behavioral responses, whereas these effects were either absent or less pronounced in the CO2 extract treated groups. By contrast, serotoninergic effects of the CO2 extract were more pronounced than those of the alcoholic extract. These and various other observations made during the study confirm that although the antidepressant action of hypericum extracts depends on their hyperforin contents, their spectrums of central activity are due to other component(s). Our working hypothesis that hyperforin and serotoninergic mechanisms are involved in the therapeutically observed antidepressant activities of hypericum extracts is in agreement with these observations.

Inhibition of Synaptosomal Uptake of 3H-L-glutamate and 3H-GABA by Hyperforin, a Major Constituent of St. John's Wort The Role of Amiloride Sensitive Sodium Conductive Pathways

“…In agreement with its clinical efficacy, hypericum extract is also active in a large number of biochemical and behavioral models which are indicative of antidepressant activity (Butterweck et al 1997;Müller et al 1997;Bhattacharya et al 1998;Chatterjee et al 1998aChatterjee et al , 1998bGambarana et al 1999). As possible mechanism of action an inhibition 3 H-L-glutamate and 3 H-GABA Uptake 189 of the neuronal uptake of serotonin, norepinephrine and dopamine has been demonstrated (Müller et al 1997;Neary and Bu 1999).…”

The experimental and clinical pharmacology of St John's Wort (Hypericum perforatum L.)

“…55,56 More recently antidepressant activity of hypericum was also observed in the learned helplessness test, which is also used in detecting potential antidepressants. 57 The efficacy of the hypericum extract in these two models was correlated with their hyperforin contents, [56][57][58] suggesting that the hyperforin content may be the active constituent in hypericum extracts responsible for antidepressant activity. This also supports recent evidence that hyperforin is also the major bio-active substance responsible for inhibiting synaptic re-uptake of monoamines.…”

St John's wort and imipramine-induced gene expression profiles identify cellular functions relevant to antidepressant action and novel pharmacogenetic candidates for the phenotype of antidepressant treatment response

“…CMC has been used to dissolve SJW as described previously. 14,26 Control animals consisted of rats injected with vehicle (0.9% saline) i.p. for the IMI-treated group or gavaged with vehicle (0.3% CMC) for the SJW-treated group.…”