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

S. Chatterjee, V. Filippov, P. Lishko, O. Maximyuk, M. Nöldner, O. Krishtal

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Effects of hyperforin, an acylphloroglucinol derivative isolated from antidepressive medicinal herb Hypericum perforatum (St. John's Wort), on voltage- and ligand-gated ionic conductances were investigated. Whole-cell patch clamp and concentration clamp techniques on acutely isolated hippocampal pyramidal neurons and on cerebellar Purkinje neurons of rat were used. At concentrations between 3 to 100 μM hyperforin induced a dose and time dependent inward current which completely stabilized within a few seconds. Although 1 μM hyperforin inhibited virtually all investigated conductances (GABA ≥ I(Ca(N)) > I(Na) ≥ I(Ca(P)) ≥ AMPA ≥ I(K(A)) > NMDA > I(K(DR))), its effects on several of them could not be reversed by repeated washings. Dose response studies revealed that although AMPA induced current is inhibited by hyperforin in a competitive manner, these responses are not completely blocked by very high concentration of the agent. On the contrary, however, NMDA receptor-activated ionic conductance could be completely and uncompetitively inhibited by the agent. Taken together these observation not only reconfirm that hyperforin is a major neuroactive component of hypericum extracts but also demonstrate that this structurally unique and naturally abundant molecule is a potent modulation of mechanism involved in the control of neuronal ionic conductances. Various observed effects of hyperforin do not, however, seem to be mediated by one single molecular mechanism of action of the agent.

Original languageEnglish
Pages (from-to)2395-2405
Number of pages11
JournalLife Sciences
Issue number22
StatePublished - Oct 22 1999


  • AMPA
  • Antagonism
  • Cerebellar Purkinje neurons
  • Hippocampal pyramidal neurons
  • Hyperforin
  • Hypericum extract
  • Ion channels
  • NMDA
  • Patch clamp technique


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