ArticleScientific reports2014
Protonophore properties of hyperforin are essential for its pharmacological activity.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 60 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
- Ambigols Uncouple Oxidative Phosphorylation In Vitro.ACS chemical biology · 2026Article
- TRPC6-Mediated CaCells · 2026Article
- Hyperforin potentiates polymyxin B against multidrug-resistant Gram-negative pathogens via membrane disruption, biofilm eradication, and oxidative stress.Antimicrobial agents and chemotherapy · 2025Article
- Polyprenylated Acylphloroglucinols fromPharmaceuticals (Basel, Switzerland) · 2025Article
- N-N-Substituted Piperazine, Cmp2, Improves Cognitive and Motor Functions in 5xFAD Mice.International journal of molecular sciences · 2025Article
- Documentary Analysis ofPharmaceuticals (Basel, Switzerland) · 2024Review
- Identification of molecular targets of Hypericum perforatum in blood for major depressive disorder: a machine-learning pharmacological study.Chinese medicine · 2024Article
- Role of Neuronal TRPC6 Channels in Synapse Development, Memory Formation and Animal Behavior.International journal of molecular sciences · 2023Review
- Review
- Hyperforin Elicits Cytostatic/Cytotoxic Activity in Human Melanoma Cell Lines, Inhibiting Pro-Survival NF-κB, STAT3, AP1 Transcription Factors and the Expression of Functional Proteins Involved in Mitochondrial and Cytosolic Metabolism.International journal of molecular sciences · 2023Article
- Analysis of hyperforin (St. John's wort) action at TRPC6 channel leads to the development of a new class of antidepressant drugs.Molecular psychiatry · 2022Article
- New Positive TRPC6 Modulator Penetrates Blood-Brain Barrier, Eliminates Synaptic Deficiency and Restores Memory Deficit in 5xFAD Mice.International journal of molecular sciences · 2022Article
- How Should the Worldwide Knowledge of Traditional Cancer Healing Be Integrated with Herbs and Mushrooms into Modern Molecular Pharmacology?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke.International journal of molecular sciences · 2021Review
- Synthesis and Multiplexed Activity Profiling of Synthetic Acylphloroglucinol Scaffolds.Angewandte Chemie (International ed. in English) · 2021Article
- Anti-Tumor Activity ofAntioxidants (Basel, Switzerland) · 2020Review
- Probing the therapeutic potential of TRPC6 for Alzheimer's disease in live neurons from patient-specific iPSCs.Journal of molecular cell biology · 2020Article
- TRPC channels: Structure, function, regulation and recent advances in small molecular probes.Pharmacology & therapeutics · 2020Review
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperforin is a pharmacologically active component of the medicinal plant Hypericum perforatum (St. John's wort), recommended as a treatment for a range of ailments including mild to moderate depression. Part of its action has been attributed to TRPC6 channel activation. We found that hyperforin induces TRPC6-independent H(+) currents in HEK-293 cells, cortical microglia, chromaffin cells and lipid bilayers. The latter demonstrates that hyperforin itself acts as a protonophore. The protonophore activity of hyperforin causes cytosolic acidification, which strongly depends on the holding potential, and which fuels the plasma membrane sodium-proton exchanger. Thereby the free intracellular sodium concentration increases and the neurotransmitter uptake by Na(+) cotransport is inhibited. Additionally, hyperforin depletes and reduces loading of large dense core vesicles in chromaffin cells, which requires a pH gradient in order to accumulate monoamines. In summary the pharmacological actions of the "herbal Prozac" hyperforin are essentially determined by its protonophore properties shown here.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.