Antidepressant Activity of Hypericum Perforatum and Hyperforin: the Neglected Possibility

Abstract

Efforts leading to the identification of hyperforin as an antidepressive component of therapeutically used alcoholic hypericum extracts are described and discussed. Initially, the effects of this unique and major constituent of the herb were detected in peripheral organs using in vitro models and an extract was obtained by supercritical extraction of the herb by carbon dioxide. These extracts are highly enriched in hyperforin (38.8%) and are devoid of hypericines and numerous other components of alcoholic extracts. Studies with such an extract and with isolated hyperforin indicated that this acylphloroglucinol derivative can inhibit serotonin-induced responses and uptake of this neurotransmitter in peritoneal cells. Assuming that the effects of hyperforin were due to its actions on serotoninergic 5-HT3/5-HT4 receptors, further studies were conducted to investigate its effects on the CNS. These efforts revealed its antidepressant activity in the behavioral despair test and led to the working hypothesis that hyperforin and serotoninergic mechanisms are involved in the antidepressant activities of alcoholic hypericum extracts. The observations made during this study also indicate that hyperforin is the major, but not the only antidepressive component of alcoholic extracts.

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).…”

“…It is a potent inhibitor of the uptake of serotonin, norepinephrine and dopamine, it is active in several biochemical and behavioral models of antidepressant activity (Bhattacharya et al 1998;Chatterjee et al 1998aChatterjee et al , 1998bMüller et al 1997), it is responsible for specific changes of the rat and human EEG typically seen for specific serotonin reuptake inhibitors Schellenberg et al 1998) and it elevates extracellular concentrations of serotonin, norepinephrine, and dopamine in the rat brain after i.p. administration (Kaehler et al 1999).…”

St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase C γ and ɛ activity

“…The most common SJW preparations used are hydroalcoholic extracts of the aerial portion of the plant that contain at least ten different kinds of biochemical compounds [16]. SJW interacts with the monoaminergic system through different mechanisms: the MAO-inhibitory properties of SJW were mainly due to hypericin [17,18] whereas the inhibition of serotonin, dopamine and noradrenaline synaptosomal uptake is related to the presence of hyperforin [19][20][21][22]. It has therefore been suggested that SJW may induce antidepressant activity through a mechanism similar to TCAs [23].…”

Hyperforin-Containing Extracts of St John's Wort Fail to Alter Gene Transcription in Brain Areas Involved in HPA Axis Control in a Long-Term Treatment Regimen in Rats

“…However, besides hypericin, pharmacological research on SJW has focused on either lipophilic extracts obtained with hypercritical CO 2 that were devoid of hypericins and flavonoids, but enriched with hyperforin (Bhattacharya et al, 1998;Chatterjee et al, 1998b;Dimpfel et al, 1998;Franklin and Cowen, 2001;Gobbi et al, 2001;Simmen et al, 1999), or hydroalcoholic extracts that were standardized on a certain amount of hyperforin (Chatterjee et al, 1996(Chatterjee et al, , 1998bDimpfel et al, 1998;Franklin and Cowen, 2001;Gobbi et al, 2001;Simmen et al, 1999Simmen et al, , 2001Wonnemann et al, 2001). The phloroglucinol derivative hyperforin has recently become a molecule of increasing interest.…”