Evidence mapPaperPMID 39019111Full record

ArticleJournal of advanced research2025

Hyperibone J exerts antidepressant effects by targeting ADK to inhibit microglial P2X7R/TLR4-mediated neuroinflammation.

Ting Li, Yawei Li, Jinhu Chen, Miaomiao Nan, Xin Zhou, Lifang Yang, Wenjun Xu, Chao Zhang, Lingyi Kong

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Ting LiJiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Shenzhen Research Institute, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Yawei LiJiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Shenzhen Research Institute, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Jinhu ChenJiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Shenzhen Research Institute, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Miaomiao NanJiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Shenzhen Research Institute, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Xin ZhouJiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Shenzhen Research Institute, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Lifang YangSchool of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning 530008, China.
Wenjun XuJiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Shenzhen Research Institute, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: wjxu@cpu.edu.cn.
Chao ZhangJiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Shenzhen Research Institute, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: zhangchao@cpu.edu.cn.
Lingyi KongJiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Shenzhen Research Institute, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: cpu_lykong@126.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Adenosine KinaseAntidepressive AgentsBenzofuransDepressionMicrogliaNeuroinflammatory DiseasesReceptors, Purinergic P2X7Toll-Like Receptor 4AnimalsDisease Models, AnimalHypericumLipopolysaccharidesMaleMiceMice, Inbred C57BLSignal TransductionAdenosine KinaseAntidepressive AgentsBenzofuransLipopolysaccharidesReceptors, Purinergic P2X7Tlr4 protein, mouseToll-Like Receptor 4ADKDepressionNeuroinflammationNF-κBP2X7RTLR4

Identifiers

PMID39019111
PMCPMC12147645

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.