ArticlePloS one2018
Antidepressive and anxiolytic effects of ostruthin, a TREK-1 channel activator.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Review
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- Article
- Effect of chronic administration of ostruthin on depression-like behavior in chronically stressed mice.IBRO neuroscience reports · 2024Article
- Simple Coumarins fromInternational journal of molecular sciences · 2023Article
- Hogweed Seed Oil: Physico-Chemical Characterization, LC-MS Profile, and Neuroprotective Activity ofLife (Basel, Switzerland) · 2023Article
- Therapeutic Effects of Coumarins with Different Substitution Patterns.Molecules (Basel, Switzerland) · 2023Review
- Synergistic effects of agonists and two-pore-domain potassium channels on secretory responses of human pancreatic duct cells Capan-1.Pflugers Archiv : European journal of physiology · 2023Article
- Cardiovascular therapeutics: A new potential for anxiety treatment?Medicinal research reviews · 2022Review
- Interaction of Medicinal Plants and Their Active Constituents With Potassium Ion Channels: A Systematic Review.Frontiers in pharmacology · 2022Review
- Two-Pore-Domain Potassium (KCells · 2021Review
- Coumarins fromInternational journal of molecular sciences · 2021Article
- Chemical Profiles and Pharmacological Properties with in Silico Studies onMolecules (Basel, Switzerland) · 2021Article
- Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress.Nutrients · 2020Review
- Antidepressive effect of an inward rectifier K+ channel blocker peptide, tertiapin-RQ.PloS one · 2020Article
- Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We screened a library of botanical compounds purified from plants of Vietnam for modulators of the activity of a two-pore domain K+ channel, TREK-1, and we identified a hydroxycoumarin-related compound, ostruthin, as an activator of this channel. Ostruthin increased whole-cell TREK-1 channel currents in 293T cells at a low concentration (EC50 = 5.3 μM), and also activity of the TREK-2 channel (EC50 = 3.7 mM). In contrast, ostruthin inhibited other K+ channels, e.g. human ether-à-go-go-related gene (HERG1), inward-rectifier (Kir2.1), voltage-gated (Kv1.4), and two-pore domain (TASK-1) at higher concentrations, without affecting voltage-gated potassium channel (KCNQ1 and 3). We tested the effect of this compound on mouse anxiety- and depression-like behaviors and found anxiolytic activity in the open-field, elevated plus maze, and light/dark box tests. Of note, ostruthin also showed antidepressive effects in the forced swim and tail suspension tests, although previous studies reported that inhibition of TREK-1 channels resulted in an antidepressive effect. The anxiolytic and antidepressive effect was diminished by co-administration of a TREK-1 blocker, amlodipine, indicating the involvement of TREK-1 channels. Administration of ostruthin suppressed the stress-induced increase in anti-c-Fos immunoreactivity in the lateral septum, without affecting immunoreactivity in other mood disorder-related nuclei, e.g. the amygdala, paraventricular nuclei, and dorsal raphe nucleus. Ostruthin may exert its anxiolytic and antidepressive effects through a different mechanism from current drugs.
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