Evidence map›Paper›PMID 27108601›Full record

ArticleActa pharmacologica Sinica2016

A novel GSK-3β inhibitor YQ138 prevents neuronal injury induced by glutamate and brain ischemia through activation of the Nrf2 signaling pathway.

Tao Pang, Yun-Jie Wang, Yuan-Xue Gao, Yuan Xu, Qiu Li, Yu-Bo Zhou, Lei Xu, Zhang-Jian Huang, Hong Liao, Lu-Yong Zhang and 3 more

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

Article in Acta pharmacologica Sinica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.1field-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

20 citing papers in PubMed, 40 citations in OpenAlex.

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  9. Protective Effect ofFrontiers in pharmacology · 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

13 authors at 4 institutions in 1 country.

Tao PangJiangsu Key Laboratory of Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Yun-Jie WangJiangsu Key Laboratory of Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Yuan-Xue GaoJiangsu Key Laboratory of Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Yuan XuJiangsu Key Laboratory of Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Qiu LiState Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou 310032, China.
Yu-Bo ZhouNational Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Lei XuNational Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zhang-Jian HuangJiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
Hong LiaoJiangsu Key Laboratory of Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Lu-Yong ZhangJiangsu Key Laboratory of Drug Screening and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Jian-Rong GaoState Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou 310032, China.
Qing YeState Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou 310032, China.
Jia LiNational Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
China Pharmaceutical University · CNZhejiang University of Technology · CNNational Center for Drug Screening · CNShanghai Institute of Materia Medica · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimTo discover neuroprotective compounds and to characterize the discovered active compound YQ138 as a novel GSK-3β inhibitor.

methodsPrimary rat cerebellar granule cells (CGCs) were treated with glutamate, and cell viability was analyzed with MTT assay, which was used as in vitro model for screening neuroprotective compounds. Active compound was further tested in OGD- or serum deprivation-induced neuronal injury models. The expression levels of GSK-3β downstream proteins (Nrf2, HO-1, NQO1, Tau and β-catenin) were detected with Western blotting. For evaluating the neuroprotective effects in vivo, adult male rats were subjected to transient middle cerebral artery occlusion (tMCAO), then treated with YQ138 (10 mg/kg, iv) at 2, 4 and 6 h after ischemia onset.

resultsFrom a compound library consisting of about 2000 potential kinase inhibitors, YQ138 was found to exert neuroprotective effects: pretreatment with YQ138 (0.1-40 μmol/L) dose-dependently inhibited glutamate-induced neuronal death. Furthermore, pretreatment with YQ138 (10 μmol/L) significantly inhibited OGD- or serum deprivation-induced neuronal death. Among a panel of seven kinases tested, YQ138 selectively inhibited the activity of GSK-3β (IC50=0.52 nmol/L). Furthermore, YQ138 dose-dependently increased the expression of β-catenin, and decreased the phosphorylation of Tau in CGCs. Moreover, YQ138 significantly increased the expression of GSK-3β downstream antioxidative proteins Nrf2, HO-1, NQO1, GSH and SOD in CGCs. In rats with tMCAO, administration of YQ138 significantly decreased infarct volume, improved the neurological deficit, and increased the expression of Nrf2 and HO-1 and the activities of SOD and GSH in the cerebral cortex.

conclusionA novel GSK-3β inhibitor YQ138 effectively suppresses brain ischemic injury in vitro and in vivo.

Indexed as

AnimalsBrainBrain IschemiaCells, CulturedGlutamic AcidGlycogen Synthase Kinase 3 betaMaleMolecular Docking SimulationNeuronsNeuroprotective AgentsNF-E2-Related Factor 2Protein Kinase InhibitorsRatsRats, Sprague-DawleySignal TransductionGlutamic AcidGlycogen Synthase Kinase 3 betaGsk3b protein, ratNeuroprotective AgentsNfe2l2 protein, ratNF-E2-Related Factor 2Protein Kinase Inhibitors

Identifiers

PMID27108601
PMCPMC4954771
OpenAlexW2344067165

What OpenQuestion holds

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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.