ArticleMolecules (Basel, Switzerland)2023
Hypericin Ameliorates Depression-like Behaviors via Neurotrophin Signaling Pathway Mediating m6A Epitranscriptome Modification.
Article in Molecules (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1 citations in OpenAlex.
- Recent developments in omics studies and artificial intelligence in depression and suicide.Translational psychiatry · 2025Pooled it
- Phytochemicals in the treatment of patients with depression: a systemic review.Frontiers in psychiatry · 2024Pooled it
- Hypericin and berberine promote elongation of hair peg-like sprouting in hair follicle organoids via oxytocin signaling activation.Scientific reports · 2026Article
- Wild Flora Species from Romania with Anxiolytic and Antidepressant Potential: A Global Perspective-Narrative Review.Biomedicines · 2026Review
- Hypericin as a Photodynamic Immunomodulator: A Natural Compound for Dermatological Therapy.Drug design, development and therapy · 2026Review
- Rewriting the brain: m6A RNA methylation as an emerging epitranscriptomic regulator in major depressive disorder.Frontiers in molecular neuroscience · 2026Review
- Whole transcriptome sequencing to uncover CircRNA expression patterns linked to schizophrenia pathogenesis.European journal of medical research · 2025Article
- Supplementary approaches to perinatal depression: a review of pathogenesis, herbal interventions, and dietary supplements.Frontiers in psychology · 2025Review
- St. John's wort extract Ze 117 alters the membrane fluidity of C6 glioma cells by influencing cellular cholesterol metabolism.Scientific reports · 2024Article
- Formulation, Characterization, and Evaluation of β-Cyclodextrin Functionalized Hypericin Loaded Nanocarriers.ACS omega · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Hypericin, one of the major antidepressant constituents of St. John's wort, was shown to exert antidepressant effects by affecting cerebral CYP enzymes, serotonin homeostasis, and neuroinflammatory signaling pathways. However, its exact mechanisms are unknown. Previous clinical studies reported that the mRNA modification N6-methyladenosine (m6A) interferes with the neurobiological mechanism in depressed patients, and it was also found that the antidepressant efficacy of tricyclic antidepressants (TCAs) is related to m6A modifications. Therefore, we hypothesize that the antidepressant effect of hypericin may relate to the m6A modification of epitranscriptomic regulation. We constructed a UCMS mouse depression model and found that hypericin ameliorated depressive-like behavior in UCMS mice. Molecular pharmacology experiments showed that hypericin treatment upregulated the expression of m6A-modifying enzymes METTL3 and WTAP in the hippocampi of UCMS mice. Next, we performed MeRIP-seq and RNA-seq to study m6A modifications and changes in mRNA expression on a genome-wide scale. The genome-wide m6A assay and MeRIP-qPCR results revealed that the m6A modifications of Akt3, Ntrk2, Braf, and Kidins220 mRNA were significantly altered in the hippocampi of UCMS mice after stress stimulation and were reversed by hypericin treatment. Transcriptome assays and qPCR results showed that the Camk4 and Arhgdig genes might be related to the antidepressant efficacy of hypericin. Further gene enrichment results showed that the differential genes were mainly involved in neurotrophic factor signaling pathways. In conclusion, our results show that hypericin upregulates m6A methyltransferase METTL3 and WTAP in the hippocampi of UCMS mice and stabilizes m6A modifications to exert antidepressant effects via the neurotrophin signaling pathway. This suggests that METTL3 and WTAP-mediated changes in m6A modifications may be a potential mechanism for the pathogenesis of depression and the efficacy of antidepressants, and that the neurotrophin signaling pathway plays a key role in this process.
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