ArticleJournal of advanced research2025
Hyperibone J exerts antidepressant effects by targeting ADK to inhibit microglial P2X7R/TLR4-mediated neuroinflammation.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Natural antidepressants in neuroimmunomodulation: molecular mechanisms, action targets, and therapeutic potential.Frontiers in immunology · 2025Pooled it
- Aspirin alleviates long-term high-fat diet-induced depressive-like behavior in male mice via suppressing arachidonic acid-mediated microglial activation and neuroinflammation.Molecular psychiatry · 2026Article
- Neointimal hyperplasia and vascular restenosis: from molecular mechanisms to therapeutic interventions.Molecular biomedicine · 2026Review
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- The analgesic effect of electroacupuncture in alleviating paclitaxel-induced peripheral neuropathic pain and its possible mechanism relates to TLR4/P2X7-NLRP3 signaling pathway.Purinergic signalling · 2026Article
- ATP and major affective disorders: the involvement of P2X receptors in pathophysiology.Purinergic signalling · 2026Review
- Calponin-3 is associated with epilepsy through the regulation of astrocyte activity.Brain pathology (Zurich, Switzerland) · 2026Article
- FENDRR-mediated regulation of osteoclast differentiation through the miRNA-129-5p/P2X7R axis.Journal of orthopaedic surgery and research · 2026Article
- Mitochondrial DNA drives NLRP3-IL-1β axis activation in microglia by binding to NLRP3, leading to neurodegeneration in Parkinson's disease models.Cell death & disease · 2026Article
- PUF, a biflavone monomer, triggers DNA damage through SLC25A15 downregulation and purine metabolic suppression in DLBCL.Journal of translational medicine · 2026Article
- NLRP3/GSDMD-dependent neutrophil extracellular traps exacerbate microglia-mediated neuroinflammation following traumatic brain injury.Cell communication and signaling : CCS · 2026Article
- HSP60 Mediates NLRP3 Inflammasome-Dependent Microglial Pyroptosis Via the TLR4/MyD88/NF-κB Signaling Axis After Subarachnoid Hemorrhage.Inflammation · 2026Article
- The therapeutic potential of compounds from natural products for alleviating depression by targeting P2X7 receptor-mediated proinflammatory signaling pathways.Frontiers in immunology · 2026Review
- STAT3 signaling is associated with neuroimmune dysregulation in a Dravet syndrome model and pediatric drug-resistant epilepsy.Frontiers in neuroscience · 2026Article
- Landscape of gene fusions in hormone receptor-positive breast cancer reveals ADK fusions as drivers of progression and potential therapeutic targets.Cell discovery · 2025Article
- The interplay between metabolism and neuroinflammation in epilepsy: mechanisms and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Novel intranasal delivery of sihosogansan demonstrates rapid antidepressant activity via GABAergic and BDNF/TrkB pathways: identification of potential bioactive quality markers.Chinese medicine · 2025Article
- Improving epilepsy management by targeting P2 × 7 receptor with ROS/electric responsive nanomicelles.Journal of nanobiotechnology · 2025Article
- Investigating the mechanisms of Sini San in alleviating inflammatory responses via multi-omics and the BDNF/TrkB/PI3K/AKT signaling pathway in depressive model rats.Frontiers in psychiatry · 2025Article
- Black ginseng under forest as a natural antidepressant: insights into its active components and mechanisms.Frontiers in chemistry · 2025Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe antidepressant properties of Hypericum species are known. Hyperibone J, a principal component found in the flowers of Hypericum bellum, exhibited in vitro anti-inflammatory effects. However, the antidepressant effects and mechanisms of Hyperibone J remain to be elucidated. Adenosine kinase (ADK) is upregulated in epilepsy and depression and has been implicated in promoting neuroinflammation.
objectivesThis study aimed to explore the impact of Hyperibone J on neuroinflammation-mediated depression and the mechanism underlying this impact.
methodsThis study employed acute and chronic in vivo depression models and an in vitro LPS-induced depression model using BV-2 microglia. The in vivo antidepressant efficacy of Hyperibone J was assessed through behavioral assays. Techniques such as RNA-seq, western blot, qPCR and ELISA were utilized to elucidate the direct target and mechanism of action of Hyperibone J.
resultsCompared with the model group, depression-like behaviors were significantly alleviated in the Hyperibone J group. Furthermore, Hyperibone J mitigated hippocampal neuroinflammation and neuronal damage. RNA-seq suggested that Hyperibone J predominantly influenced inflammation-related pathways. In vitro experiments revealed that Hyperibone J reversed the LPS-induced overexpression and release of inflammatory factors. Network pharmacology and various molecular biology experiments revealed that the potential binding of Hyperibone J at the ASN-312 site of ADK diminished the stability and protein expression of ADK. Mechanistic studies revealed that Hyperibone J attenuated the ADK/ATP/P2X7R/Caspase-1-mediated maturation and release of IL-1β. The study also revealed a significant correlation between Tlr4 expression and depression-like behaviors in mice. Hyperibone J downregulated ADK, inhibiting Tlr4 transcription, which in turn reduced the phosphorylation of NF-κB and the subsequent transcription of Nlrp3, Il-1b, Tnf, and Il-6.
conclusionHyperibone J exerted antineuroinflammatory and antidepressant effects by binding to ADK in microglia, reducing its expression and thereby inhibiting the ATP/P2X7R/Caspase-1 and TLR4/NF-κB pathways. This study provides experimental evidence for the therapeutic potential of Hypericum bellum.
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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 Socratic graph.