1. Startpage
  2. Johannes Gutenberg-Universität Mainz
  3. DFG-491381577-H
Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8402
Full metadata record
DC FieldValueLanguage
dc.contributor.authorEl Hamdaoui, Yamina-
dc.contributor.authorZheng, Fang-
dc.contributor.authorFritz, Nikolas-
dc.contributor.authorYe, Lian-
dc.contributor.authorTran, Mai Anh-
dc.contributor.authorSchwickert, Kevin-
dc.contributor.authorSchirmeister, Tanja-
dc.contributor.authorBraeuning, Albert-
dc.contributor.authorLichtenstein, Dajana-
dc.contributor.authorHellmich, Ute A.-
dc.contributor.authorWeikert, Dorothee-
dc.contributor.authorHeinrich, Markus-
dc.contributor.authorTreccani, Giulia-
dc.contributor.authorSchäfer, Michael K. E.-
dc.contributor.authorNowak, Gabriel-
dc.contributor.authorNürnberg, Bernd-
dc.contributor.authorAlzheimer, Christian-
dc.contributor.authorMüller, Christian P.-
dc.contributor.authorFriedland, Kristina-
dc.date.accessioned2023-01-18T12:21:40Z-
dc.date.available2023-01-18T12:21:40Z-
dc.date.issued2022-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/8418-
dc.description.abstractSt. John’s wort is an herb, long used in folk medicine for the treatment of mild depression. Its antidepressant constituent, hyperforin, has properties such as chemical instability and induction of drug-drug interactions that preclude its use for individual pharmacotherapies. Here we identify the transient receptor potential canonical 6 channel (TRPC6) as a druggable target to control anxious and depressive behavior and as a requirement for hyperforin antidepressant action. We demonstrate that TRPC6 deficiency in mice not only results in anxious and depressive behavior, but also reduces excitability of hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. Using electrophysiology and targeted mutagenesis, we show that hyperforin activates the channel via a specific binding motif at TRPC6. We performed an analysis of hyperforin action to develop a new antidepressant drug that uses the same TRPC6 target mechanism for its antidepressant action. We synthesized the hyperforin analog Hyp13, which shows similar binding to TRPC6 and recapitulates TRPC6-dependent anxiolytic and antidepressant effects in mice. Hyp13 does not activate pregnan-X-receptor (PXR) and thereby loses the potential to induce drug-drug interactions. This may provide a new approach to develop better treatments for depression, since depression remains one of the most treatment-resistant mental disorders, warranting the development of effective drugs based on naturally occurring compounds.en_GB
dc.description.sponsorshipGefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577de
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleAnalysis of hyperforin (St. John’s wort) action at TRPC6 channel leads to the development of a new class of antidepressant drugsen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-8402-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 09 Chemie, Pharmazie u. Geowissensch.de
jgu.organisation.departmentFB 04 Medizin-
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleMolecular psychiatryde
jgu.journal.volume27de
jgu.pages.start5070de
jgu.pages.end5085de
jgu.publisher.year2022-
jgu.publisher.nameSpringerde
jgu.publisher.issn1476-5578de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.1038/s41380-022-01804-3de
jgu.organisation.rorhttps://ror.org/023b0x485-
jgu.subject.dfgLebenswissenschaftende
Appears in collections:DFG-491381577-H

Files in This Item:
  File Description SizeFormat
Thumbnail
analysis_of_hyperforin_st_joh-20230118131954936.pdf3.88 MBAdobe PDFView/Open
Show simple item record