Evidence map›Paper›PMID 30260985›Full record

ArticlePloS one2018

Cilostazol disrupts TLR-4, Akt/GSK-3β/CREB, and IL-6/JAK-2/STAT-3/SOCS-3 crosstalk in a rat model of Huntington's disease.

Hanan El-Abhar, Mai A Abd El Fattah, Walaa Wadie, Dalia M El-Tanbouly

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
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

32 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
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  17. Cilostazol Combats Lipopolysaccharide-Induced Hippocampal Injury in Rats: Role of AKT/GSK3Advances in pharmacological and pharmaceutical sciences · 2024
    Article
  18. Article
  19. Review
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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

4 authors at 1 institution in 1 country.

Hanan El-AbharDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.ORCID 0000-0001-8819-9891
Mai A Abd El FattahDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Walaa WadieDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Dalia M El-TanboulyDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Cairo University · EG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Countless neurodegenerative diseases are associated with perverse multiple targets of cyclic nucleotide signalling, hastening neuronal death. Cilostazol, a phosphodiesterase-III inhibitor, exerts neuroprotective effects against sundry models of neurotoxicity, however, its role against Huntington's disease (HD) has not yet been tackled. Hence, its modulatory effect on several signalling pathways using the 3-nitropropionic acid (3-NP) model was conducted. Animals were injected with 3-NP (10 mg/kg/day, i.p) for two successive weeks with or without the administration of cilostazol (100 mg/kg/day, p.o.). Contrary to the 3-NP effects, cilostazol largely preserved striatal dopaminergic neurons, improved motor coordination, and enhanced the immunohistochemical reaction of tyrosine hydroxylase enzyme. The anti-inflammatory effect of cilostazol was documented by the pronounced reduction of the toll like receptor-4 (TLR-4) protein expression and the inflammatory cytokine IL-6, but with a marked elevation in IL-10 striatal contents. As a consequence, cilostazol reduced IL-6 downstream signal, where it promoted the level of suppressor of cytokine signalling 3 (SOCS3), while abated the phosphorylation of Janus Kinase 2 (JAK-2) and Signal transducers and activators of transcription 3 (STAT-3). Phosphorylation of the protein kinase B/glycogen synthase kinase-3β/cAMP response element binding protein (Akt/GSK-3β/CREB) cue is another signalling pathway that was modulated by cilostazol to further signify its anti-inflammatory and antiapoptotic capacities. The latter was associated with a reduction in the caspase-3 expression assessed by immunohistochemical assay. In conclusion the present study provided a new insight into the possible mechanisms by which cilostazol possesses neuroprotective properties. These intersecting mechanisms involve the interference between TLR-4, IL-6-IL-10/JAK-2/STAT-3/SOCS-3, and Akt/GSK-3β/CREB signalling pathways.

Indexed as

AnimalsApoptosisCilostazolCorpus StriatumCREB-Binding ProteinCyclic AMP Response Element-Binding ProteinDisease Models, AnimalGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHuntington DiseaseInterleukin-6Janus Kinase 2MaleNeuroprotective AgentsNitro CompoundsPhosphatidylinositol 3-Kinases3-nitropropionic acidCilostazolCREB-Binding ProteinCrebbp protein, ratCyclic AMP Response Element-Binding ProteinGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaInterleukin-6Janus Kinase 2Neuroprotective AgentsNitro CompoundsPhosphatidylinositol 3-KinasesPropionatesProto-Oncogene Proteins c-aktSocs3 protein, ratSTAT2 Transcription FactorStat3 protein, ratSTAT3 Transcription FactorSuppressor of Cytokine Signaling 3 ProteinTlr4 protein, ratToll-Like Receptor 4

Identifiers

PMID30260985
PMCPMC6160003
OpenAlexW2893356404

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.