Evidence map›Paper›PMID 27864733›Full record

ArticleMolecular neurobiology2017

(-)-Epicatechin, a Natural Flavonoid Compound, Protects Astrocytes Against Hemoglobin Toxicity via Nrf2 and AP-1 Signaling Pathways.

Xi Lan, Xiaoning Han, Qian Li, Jian Wang

Abstract read
In one paragraph

Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

  1. Pooled it
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  16. An enriched environment improves long-term functional outcomes in mice after intracerebral hemorrhage by mechanisms that involve the Nrf2/BDNF/glutaminase pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Article
  17. Review
  18. The Role of Ferroptosis in Blood-Brain Barrier Injury.Cellular and molecular neurobiology · 2023
    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 2 institutions in 1 country.

Xi LanDepartment of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross Bldg 370B, Baltimore, MD, 21205, USA.
Xiaoning HanDepartment of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross Bldg 370B, Baltimore, MD, 21205, USA.
Qian LiDepartment of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross Bldg 370B, Baltimore, MD, 21205, USA.
Jian WangDepartment of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross Bldg 370B, Baltimore, MD, 21205, USA. jwang79@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Neuroprotective effect of flavanol (-) epicatechin after intracerebral hemorrhageR01AT007317 · NCCIH · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2012 to 2016
$2.0M
PGE2 EP1 and EP3 receptors as therapeutic targets in intracerebral hemorrhageR01NS078026 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2012 to 2016
$1.8M
American Heart Association 13GRNT15730001National Institutes of Health R01AT007317National Institutes of Health R01NS078026NCCIH NIH HHS R01 AT007317NINDS NIH HHS R01 NS078026
6 · The paper itself

Abstract

(-)-Epicatechin is a brain-permeable, natural product found at high concentrations in green tea and cocoa. Our previous research has shown that (-)-epicatechin treatment reduces hemorrhagic stroke injury via nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in vivo. However, the mechanism of action of this compound in modulation of oxidant stress and in protection against hemoglobin-induced astrocyte injury is unclear. Therefore, we explored the cellular and molecular mechanisms that underlie these protective effects in vitro. Mouse primary astrocytes isolated from wild-type mice and Nrf2 knockout (KO) mice were preconditioned with hemoglobin to simulate intracerebral hemorrhage (ICH) in vitro. Effects of (-)-epicatechin were measured by Western blotting, immunostaining, MTT assay, and reactive oxidant stress (ROS) assay. (-)-Epicatechin increased Nrf2 nuclear accumulation and cytoplasmic levels of superoxide dismutase 1 (SOD1) in wild-type astrocytes but did not increase SOD1 expression in Nrf2 knockout (KO) astrocytes. Furthermore, (-)-epicatechin treatment did not alter heme oxygenase 1 (HO1) expression in wild-type astrocytes after hemoglobin exposure, but it did decrease HO1 expression in similarly treated Nrf2 KO astrocytes. In both wild-type and Nrf2 KO astrocytes, (-)-epicatechin suppressed phosphorylated JNK and nuclear expression of JNK, c-jun, and c-fos, indicating that inhibition of activator protein-1 (AP-1) activity by (-)-epicatechin is Nrf2-independent. These novel findings indicate that (-)-epicatechin protects astrocytes against hemoglobin toxicity through upregulation of Nrf2 and inhibition of AP-1 activity. These cellular and molecular effects may partially explain the cerebroprotection as we previously observed for (-)-epicatechin in animal models of ICH.

Indexed as

AnimalsAstrocytesCatechinFlavonoidsHemoglobinsMiceNeuroprotective AgentsNF-E2-Related Factor 2Oxidative StressReactive Oxygen SpeciesSignal TransductionSuperoxide DismutaseTranscription Factor AP-1CatechinFlavonoidsHemoglobinsNeuroprotective AgentsNF-E2-Related Factor 2Reactive Oxygen SpeciesSuperoxide DismutaseTranscription Factor AP-1(−)-EpicatechinHeme oxygenase 1Intracerebral hemorrhageNuclear factor erythroid 2-related factor 2Reactive oxygen species

Identifiers

PMID27864733
PMCPMC5436959
OpenAlexW2549191670

What OpenQuestion holds

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LicenceTDM
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.