Evidence map›Paper›PMID 27977755›Full record

ArticlePloS one2016

Concurrent Treatment with Taxifolin and Cilostazol on the Lowering of β-Amyloid Accumulation and Neurotoxicity via the Suppression of P-JAK2/P-STAT3/NF-κB/BACE1 Signaling Pathways.

So Youn Park, Hae Young Kim, Hee Jeong Park, Hwa Kyoung Shin, Ki Whan Hong, Chi Dae Kim

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 55 citations in OpenAlex.

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  18. Investigating the basis for the antidepressant effects ofIranian journal of basic medical sciences · 2021
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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

6 authors at 1 institution in 1 country.

So Youn ParkDepartment of Pharmacology, School of Medicine, Pusan National University, Gyeongsangnam-do, Republic of Korea.
Hae Young KimGene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan National University, Gyeongsangnam-do, Republic of Korea.
Hee Jeong ParkGene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan National University, Gyeongsangnam-do, Republic of Korea.
Hwa Kyoung ShinDivision of Meridian and Structural Medicine, Pusan National University, Gyeongsangnam-do, Republic of Korea.
Ki Whan HongGene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan National University, Gyeongsangnam-do, Republic of Korea.
Chi Dae KimDepartment of Pharmacology, School of Medicine, Pusan National University, Gyeongsangnam-do, Republic of Korea.
Pusan National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Taxifolin is a potent flavonoid that exerts anti-oxidative effect, and cilostazol increases intracellular cAMP levels by inhibiting phosphodiesterase 3 that shows antiinflammatory actions. BACE1 (β-site APP cleaving enzyme 1) is the rate-limiting enzyme responsible for the β-cleavage of amyloid precursor proteins to Aβ peptides. In this study, endogenous Aβ and C99 accumulation was explored in N2a Swe cells exposed to 1% FBS medium. Increased Aβ and C99 levels were significantly attenuated by taxifolin alone and in combination with cilostazol. Increased phosphorylated JAK2 at Tyr1007/1008 (P-JAK), phosphorylated STAT3 at Tyr 705 (P-STAT3) expressions and increased expressions of BACE1 mRNA and protein in the activated N2a Swe cells were significantly attenuated by taxifolin (10~50 μM), cilostazol (10~50 μM) alone and in combination at minimum concentrations. In these cells, decreased cytosol IκBα expression was elevated, and increased nuclear NF-κB p65 level and nuclear NF-κB p65 DNA binding activity were significantly reduced by taxifolin and cilostazol in a similar manner. Following STAT3 gene (~70% reduction) knockdown in N2a cells, Aβ-induced nuclear NF-κB and BACE1 expressions were not observed. Taxifolin, cilostazol, or resveratrol significantly stimulated SIRT1 protein expression. In SIRT1 gene-silenced (~50%) N2a cells, taxifolin, cilostazol, and resveratrol all failed to suppress Aβ1-42-stimulated P-STAT3 and BACE1 expression. Consequently, taxifolin and cilostazol were found to significantly decrease lipopolysaccharide (1-10 μg/ml)-induced iNOS and COX-2 expressions, and nitrite production in cultured BV-2 microglia cells and to increase N2a cell viability. In conclusion, taxifolin and cilostazol strongly inhibited amyloidogenesis in a synergistic manner by suppressing P-JAK2/P-STAT3-coupled NF-κB-linked BACE1 expression via the up-regulation of SIRT1.

Indexed as

Amyloid beta-PeptidesAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesCells, CulturedCilostazolDown-RegulationDrug SynergismJanus Kinase 2MiceNeuroprotectionNeuroprotective AgentsNF-kappa BPhosphorylationQuercetinSignal TransductionAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBACE1 protein, humanCilostazolJAK2 protein, humanJanus Kinase 2Neuroprotective AgentsNF-kappa BQuercetinSTAT3 Transcription FactortaxifolinTetrazoles

Identifiers

PMID27977755
PMCPMC5158044
OpenAlexW2564326916

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.