Evidence map›Paper›PMID 40491976›Full record

ArticleFood science & nutrition2025

Molecular Mechanisms Underlying Apple Extract Ameliorates Depression-Incident Cognitive Dysfunction Based on Network Pharmacology.

Yue Chen, Shunqiang Yang, Huihuang Shi, Jizhe Cui, Zhu Li

Abstract read
In one paragraph

Article in Food science & nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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

3 citing papers in PubMed.

  1. Food science & nutrition · 2026
    Article
  2. Food science & nutrition · 2026
    Article
  3. 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

5 authors.

Yue ChenCollege of Agronomy and Life Sciences Zhaotong University Zhaotong China.
Shunqiang YangCollege of Agronomy and Life Sciences Zhaotong University Zhaotong China.
Huihuang ShiCollege of Agronomy and Life Sciences Zhaotong University Zhaotong China.
Jizhe CuiCollege of Agronomy and Life Sciences Zhaotong University Zhaotong China.
Zhu LiCollege of Agronomy and Life Sciences Zhaotong University Zhaotong China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The apple was found to be involved in antidepressant properties. Thus, this study aimed to explore the effects of apple extract (AE) on depression and to elucidate the underlying mechanisms. Our network pharmacology analysis indicated that AE may exert its antidepressant effects through the regulation of inflammatory responses and the cAMP signaling pathway. Behavioral tests showed that AE significantly improved spatial learning, exploratory behavior, anhedonia, and despair in CUMS mice. Biochemical analyses revealed that AE increased synaptic density in the hippocampus, enhanced brain levels of 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA), and reduced the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in both serum and brain tissue. In vitro, AE demonstrated significant neuroprotective effects against CORT-induced cytotoxicity. Furthermore, AE treatment upregulated the levels of cAMP, phosphorylated PKA (pPKA), and phosphorylated CREB (pCREB) while downregulating PTGS2 expression, suggesting that the cAMP/PKA/CREB/PTGS2 signaling pathway is a key mechanism underlying the antidepressant effects of AE. Therefore, our study indicated that AE can improve cognitive dysfunction and alleviate depressive-like behavior by targeting the cAMP/PKA/CREB/PTGS2 signaling pathway in CUMS mice. This study paved the way for the clinical application of AE as a novel treatment for depression and provided new targeted therapeutic strategies.

Indexed as

apple extractcAMPCUMSinflammatory responsenetwork pharmacology

Identifiers

PMID40491976
PMCPMC12146215

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.