S. Chatterjee et al., Hyperforin attenuates various ionic conductance mechanisms in the isolatedhippocampal neurons of rat, LIFE SCI, 65(22), 1999, pp. 2395-2405
Effects of hyperforin, an acylphloroglucinol derivative isolated from antid
epressive medicinal herb Hypericum perforatum (St. John's Wort), on voltage
- and ligand-gated ionic conductances were investigated. Whole-cell patch c
lamp and concentration clamp techniques on acutely isolated hippocampal pyr
amidal neurons and on cerebellar Purkinje neurons of rat were used. At conc
entrations between 3 to 100 mu M hyperforin induced a dose and time depende
nt inward current which completely stabilized within a few seconds. Althoug
h 1 mu M hyperforin inhibited virtually all investigated conductances (GABA
greater than or equal to I-Ca(N) > I-Na greater than or equal to I-Ca(P) g
reater than or equal to AMPA greater than or equal to I-K(A) > NMDA > I-K(D
R)), its effects on several of them could not be reversed by repeated washi
ngs. Dose response studies revealed that although AMPA induced current is i
nhibited by hyperforin in a competitive manner, these responses are not com
pletely blocked by very high concentration of the agent. On the contrary, h
owever, NMDA receptor-activated ionic conductance could be completely and u
ncompetitively inhibited by the agent. Taken together these observation not
only reconfirm that hyperforin is a major neuroactive component of hyperic
um extracts but also demonstrate that this structurally unique and naturall
y abundant molecule is a potent modulation of mechanism involved in the con
trol 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.