ArticleMolecular psychiatry2022
Analysis of hyperforin (St. John's wort) action at TRPC6 channel leads to the development of a new class of antidepressant drugs.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Hyperforin as a Multifunctional Specialized Metabolite of Natural Origin for Chronic Diseases: From Molecular Mechanisms to Clinical Translation.Current issues in molecular biology · 2026Review
- Wild Flora Species from Romania with Anxiolytic and Antidepressant Potential: A Global Perspective-Narrative Review.Biomedicines · 2026Review
- Comprehensive Assessment of Druggable Targets in Cortical Neurons Reveals Biological Limits of Cell Type-Specific Neuropharmacology.Biomedicines · 2026Article
- TRPC6 governs brown adipose thermogenesis via a BMPR2-p38 MAPK signaling axis.Molecular metabolism · 2026Article
- Hyperimonates A and B, a pair of unprecedented polyprenylated acylphloroglucinols fromActa pharmaceutica Sinica. B · 2026Article
- Modulation of monoaminergic neurotransmission in substance use disorders: a neuropharmacological perspective focusing on plant-derived metabolites.Frontiers in pharmacology · 2026Review
- St. John's Wort for Depression: From Neurotransmitters to Membrane Plasticity.International journal of molecular sciences · 2025Review
- Congenital Hypothyroidism Dysregulates TRPC6 to Mediate Abnormal Dendritic Spine Growth of Hippocampal Neurons.CNS neuroscience & therapeutics · 2025Article
- The Potential of Selected Plants and Their Biologically Active Molecules in the Treatment of Depression and Anxiety Disorders.International journal of molecular sciences · 2025Review
- Targeting a distinct binding pocket in the pregnane X receptor with natural agonist TRLW-2 ameliorates murine ulcerative colitis.Frontiers in pharmacology · 2025Article
- Supplementary approaches to perinatal depression: a review of pathogenesis, herbal interventions, and dietary supplements.Frontiers in psychology · 2025Review
- Documentary Analysis ofPharmaceuticals (Basel, Switzerland) · 2024Review
- St. John's wort extract Ze 117 alters the membrane fluidity of C6 glioma cells by influencing cellular cholesterol metabolism.Scientific reports · 2024Article
- Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFRCNS neuroscience & therapeutics · 2024Article
- Preventive effect of hyperforin on lipopolysaccharide-induced acute kidney injury and inflammation by repressing the NF-κB/miR-21 axis.Central-European journal of immunology · 2024Article
- Role of Neuronal TRPC6 Channels in Synapse Development, Memory Formation and Animal Behavior.International journal of molecular sciences · 2023Review
- Hypericin Ameliorates Depression-like Behaviors via Neurotrophin Signaling Pathway Mediating m6A Epitranscriptome Modification.Molecules (Basel, Switzerland) · 2023Article
- Cytotoxic and Antioxidant Activity ofMolecules (Basel, Switzerland) · 2023Article
- Current Knowledge of the Antidepressant Activity of Chemical Compounds fromPharmaceuticals (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
St. 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.
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