Evidence map›Paper›PMID 38835076›Full record

ArticleCell communication and signaling : CCS2024

A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo.

Daiki Wakasugi, Shinji Kondo, Farhana Ferdousi, Seiya Mizuno, Akira Yada, Kenichi Tominaga, Satoru Takahashi, Hiroko Isoda

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
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  10. Article
  11. Nutrients · 2024
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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

8 authors.

Daiki WakasugiTsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan.
Shinji Kondo *Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan.
Farhana Ferdousi *Tsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan.
Seiya MizunoLaboratory Animal Resource Center (LARC) in Transborder Medical Research Center (TMRC), Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
Akira YadaOpen Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305-0821, Japan.
Kenichi TominagaTsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan.
Satoru TakahashiLaboratory Animal Resource Center (LARC) in Transborder Medical Research Center (TMRC), Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
Hiroko IsodaTsukuba Life Science Innovation Program (T-LSI), University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan. isoda.hiroko.ga@u.tsukuba.ac.jp.

Funding

Japan Science and Technology Agency JPMJPF2017
6 · The paper itself

Abstract

backgroundNeuroinflammation is widely acknowledged as a characteristic feature of almost all neurological disorders and specifically in depression- and anxiety-like disorders. In recent years, there has been significant attention on natural compounds with potent anti-inflammatory effects due to their potential in mitigating neuroinflammation and neuroplasticity.

methodsIn the present study, we aimed to evaluate the neuroprotective effects of oleacein (OC), a rare secoiridoid derivative found in extra virgin olive oil. Our goal was to explore the BDNF/TrkB neurotrophic activity of OC and subsequently assess its potential for modulating neuroinflammatory response using human neuroblastoma cells (SH-SY5Y cells) and an in vivo model of depression induced by lipopolysaccharide (LPS)-mediated inflammation.

resultsIn SH-SY5Y cells, OC exhibited a significant dose-dependent increase in BDNF expression. This enhancement was absent when cells were co-treated with inhibitors of BDNF's receptor TrkB, as well as downstream molecules PI3K and MEK. Whole-transcriptomics analysis revealed that OC upregulated cell cycle-related genes under normal conditions, while downregulating inflammation-associated genes in LPS-induced conditions. Furthermore, surface plasmon resonance (SPR) assays demonstrated that OC exhibited a stronger and more stable binding affinity to TrkB compared to the positive control, 7,8-dihydroxyflavone. Importantly, bioluminescence imaging revealed that a single oral dose of OC significantly increased BDNF expression in the brains of Bdnf-IRES-AkaLuc mice. Furthermore, oral administration of OC at a dosage of 10 mg/kg body weight for 10 days significantly reduced immobility time in the tail suspension test compared to the LPS-treated group. RT-qPCR analysis revealed that OC significantly decreased the expression of pro-inflammatory cytokines Tnfα, Il6, and Il1β, while simultaneously enhancing Bdnf expression, as well as both pro and mature BDNF protein levels in mice hippocampus. These changes were comparable to those induced by the positive control antidepressant drug fluoxetine. Additionally, microarray analysis of mouse brains confirmed that OC could counteract LPS-induced inflammatory biological events.

conclusionAltogether, our study represents the first report on the potential antineuroinflammatory and antidepressant properties of OC via modulation of BDNF/TrkB neurotrophic activity. This finding underscores the potential of OC as a natural therapeutic agent for depression- and anxiety-related disorders.

Indexed as

Brain-Derived Neurotrophic FactorLipopolysaccharidesReceptor, trkBAldehydesAnimalsAnti-Inflammatory AgentsCell Line, TumorCyclopentane MonoterpenesHumansInflammationMaleMembrane GlycoproteinsMiceMice, Inbred C57BLNeuroinflammatory DiseasesNeuroprotective AgentsAldehydesAnti-Inflammatory AgentsBrain-Derived Neurotrophic FactorCyclopentane MonoterpenesLipopolysaccharidesMembrane GlycoproteinsNeuroprotective AgentsoleaceinOlive OilPhenolsReceptor, trkBtropomyosin-related kinase-B, humanBDNFBdnf-IRES-AkaLuc miceBioluminescence imagingDepressionLPSNeuroinflammationOleaceinSH-SY5Y cellsSurface plasmon resonance (SPR) assayTrkBWhole-transcriptomics

Identifiers

PMID38835076
PMCPMC11151522

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LicenceCC BY
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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.