Effects of Tetrahydrohyperforin in Mouse Hippocampal Slices: Neuroprotection, Long-term Potentiation and TRPC Channels

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dc.contributor.authorMontecinos-Oliva, C.
dc.contributor.authorSchueller, A.
dc.contributor.authorParodi, J.
dc.contributor.authorMelo, F.
dc.contributor.authorInestrosa, N. C.
dc.date.accessioned2025-01-23T21:42:27Z
dc.date.available2025-01-23T21:42:27Z
dc.date.issued2014
dc.description.abstractTetrahydrohyperforin (IDN5706) is a semi-synthetic compound derived from hyperforin (IDN5522) and is the main active principle of St. John's Wort. IDN5706 has shown numerous beneficial effects when administered to wild-type and double transgenic (APPswe/PSEN1 Delta E9) mice that model Alzheimer's disease. However, its mechanism of action is currently unknown. Toward this end, we analysed field excitatory postsynaptic potentials (fEPSPs) in mouse hippocampal slices incubated with IDN5706 and in the presence of the TRPC3/6/7 activator 1-oleoyl-2-acetyl-sn-glycerol (OAG), the TRPC channel blocker SKF96365, and neurotoxic amyloid beta-protein (A beta) oligomers. To study spatial memory, Morris water maze (MWM) behavioural tests were conducted on wild-type mice treated with IDN5706 and SKF96365. In silico studies were conducted to predict a potential pharmacophore. IDN5706 and OAG had a similar stimulating effect on fEPSPs, which was inhibited by SKF96365. IDN5706 protected from reduced fEPSPs induced by A beta oligomers. IDN5706 improved spatial memory in wild-type mice, an effect that was counteracted by co-administration of SKF96365. Our in silico studies suggest strong pharmacophore similarity of IDN5706 and other reported TRPC6 activators (IDN5522, OAG and Hyp9). We propose that the effect of IDN5706 is mediated through activation of the TRPC3/6/7 channel subfamily. The unveiling of the drug's mechanism of action is a necessary step toward the clinical use of IDN5706 in Alzheimer's disease.
dc.format.extent13 páginas
dc.fuente.origenWOS
dc.identifier.doi10.2174/0929867321666140716091229
dc.identifier.eissn1875-533X
dc.identifier.issn0929-8673
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101660
dc.identifier.urihttps://doi.org/10.2174/0929867321666140716091229
dc.identifier.wosidWOS:000341969100006
dc.issue.numero30
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final3506
dc.pagina.inicio3494
dc.revistaCurrent medicinal chemistry
dc.rightsacceso restringido
dc.subjectA beta oligomers
dc.subjectAlzheimer's Disease
dc.subjectneuroprotection
dc.subjecthippocampus
dc.subjecttetrahydrohyperforin
dc.subjectTRPC channels
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleEffects of Tetrahydrohyperforin in Mouse Hippocampal Slices: Neuroprotection, Long-term Potentiation and TRPC Channels
dc.typeartículo
dc.volumen21
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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