Hyperforin attenuates various ionic conductance mechanisms in the isolated hippocampal neurons of rat

Chatterjee, Shyam Sunder; Filippov, V. V.; Lishko, Polina V.; Maximyuk, Oleksandr; Nöldner, M.; Krishtal, O. A.

doi:10.1016/s0024-3205(99)00506-8

Cited by 64 publications

(60 citation statements)

References 22 publications

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“…Its potency in the slice assay was similar to the inhibition of NMDA currents observed in hippocampal pyramidal neurons (IC 50 = 3.2 µM). In a similar concentration range, hyperforin has been shown to inhibit AMPA receptors (IC 50 = 4.6 µM), while inhibition of neuronal voltage-dependent calcium channels of the P-type was observed in the submicromolar range (11,12). In contrast, N-and L-type calcium channels, as well as sodium channels, were not significantly affected in the presence of hyperforin (30).…”

Section: For Details)mentioning

confidence: 90%

“…These effects may be secondary to an increase of the intracellular sodium concentration mediated by openings of non-selective cation channels in the synaptosomal membrane (10). Finally, hyperforin also interacts with a variety of receptors and ion channels including glutamatergic and GABAergic receptors and calcium channels (11,12). In the present study, we tested hyperforin's actions on biological responses induced by N-methyl-D-aspartate (NMDA)-receptor activation.…”

Section: Introductionmentioning

confidence: 98%

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NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort

et al. 2006

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Abstract. Extracts of the medicinal plant St. John's wort (Hypericum perforatum) are widely used for the treatment of affective disorders. Hyperforin, a constituent of St. John's wort, is known to modulate the release and re-uptake of various neurotransmitters, an action that likely underlies its antidepressive activity. We now report that hyperforin also has N-methyl-D-aspartate (NMDA)-antagonistic effects. Hyperforin (10 µM) was found to inhibit the NMDA-induced calcium influx into cortical neurons. In rat hippocampal slices, hyperforin inhibited the NMDAreceptor-mediated release of choline from phospholipids. Hyperforin also antagonized the increase of water content in freshly isolated hippocampal slices, and it counteracted, at 3 and 10 µM, the increase of water content induced by NMDA. Hyperforin was inactive, however, in two in vivo models of brain edema formation, middle cerebral artery occlusion and water intoxication in mice. In conclusion, hyperforin has NMDA-receptor-antagonistic and potential neuroprotective effects in vitro. This effect may contribute to the therapeutic effectiveness of St. John's wort extracts in some situations, for example, for relapse prevention in alcoholism.

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Section: For Details)mentioning

confidence: 90%

Section: Introductionmentioning

confidence: 98%

NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort

et al. 2006

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“…In a recent study, the in vitro effects of LI 160 on MAO-A and MAO-B activity were investigated using mouse brain homogenates and C-serotonin and C-b-phenylethylamine probes. IC 50 concentrations of LI 160 were 120 mg ml 21 for MAO-A and 370 mg ml 21 for MAO-B. This study suggested that the potency of LI 160 for inhibiting MAO-A and MAO-B activities was too weak to be of clinical relevance at usually administered doses in MDD.…”

Section: Mechanism Of Actionmentioning

confidence: 80%

“…Plasma concentrations peaked after 2±2.6 h with hypericin and 0.4±0.6 h with pseudohypericin. The peak concentrations for hypericin were 1.5, 7.5 and 14.2 ng ml 21 , respectively, for the 300, 900 and 1800 mg doses and 2.7, 11.7 and 30.6 ng ml 21 for pseudohypericin 6 . The half-life of hypericin is reported as approximately 25 h although in practice the extract is usually dosed three times a day.…”

Section: Pharmacokineticsmentioning

confidence: 92%

Efficacy and safety of St. John's wort for the treatment of major depression

Nangia

Waqar

Doraiswamy

2000

Public Health Nutr.

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“…In addition, inhibitory effects of hyperforin on ligand-operated ion channels of AMPA, NMDA, and GABA receptors have been observed (27,39). It must be emphasized that the inhibitory effects of hyperforin on voltage-and ligand-gated ion channels have been observed at low micromolar concentrations, whereas its effects on monoamine transporters occur at nanomolar range (65,81).…”

Section: Molecular Mechanism Of Actionmentioning

confidence: 99%

Role of Hyperforin in the Pharmacological Activities of St. John's Wort

Zanoli

2004

CNS Drug Reviews

121

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The phloroglucinol derivative hyperforin has been recently shown to be a major antidepressant component in the extract of Hypericum perforatum. Experimental studies clearly demonstrated its activity in different behavioral models of depression. Moreover clinical studies linked the therapeutic efficacy of Hypericum extracts to their hyperforin content, in a dose-dependent manner.The molecular mechanism of action of hyperforin is still under investigation. Hyperforin has been shown to inhibit, like conventional antidepressants, the neuronal uptake of serotonin, norepinephrine and dopamine. However, hyperforin inhibits also the uptake of ã-aminobutyric acid (GABA) and L-glutamate. The uptake inhibition by hyperforin does not involve specific binding sites at the transporter molecules; its mechanism of action seems to be related to sodium conductive pathways, leading to an elevation in intracellular Na + concentration. Other additional mechanisms of action of hyperforin, involving ionic conductances as well synaptosomal and vesicular function, have been suggested. In addition to its antidepressant activity, hyperforin has many other pharmacological effects in vivo (anxiolytic-like, cognition-enhancing effects) and in vitro (antioxidant, anticyclooxygenase-1, and anticarcinogenic effects). These effects could be of clinical importance. On the other hand, the role of hyperforin in the pharmacological interactions occurring during Hypericum extract therapy must be fully investigated. Hyperforin seems to be responsible for the induction of liver cytochrome oxidase enzymes and intestinal P-glycoprotein.Several pharmacokinetic studies performed in rats and humans demonstrated oral bioavailability of hyperforin from Hypericum extract. Only recently a new chromatographic method for detection of hyperforin in the brain tissue has been developed and validated. Taking into account the chemical instability of hyperforin, current efforts are directed to the synthesis of new neuroactive derivatives.

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Hyperforin attenuates various ionic conductance mechanisms in the isolated hippocampal neurons of rat

Cited by 64 publications

References 22 publications

NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort

NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort

Efficacy and safety of St. John's wort for the treatment of major depression

Role of Hyperforin in the Pharmacological Activities of St. John's Wort

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