Evidence map›Paper›PMID 33067719›Full record

ArticleNeuromolecular medicine2021

Effect of Ergothioneine on 7-Ketocholesterol-Induced Endothelial Injury.

Sally Shuxian Koh, Samantha Chia-Yi Ooi, Natalie Man-Yin Lui, Cao Qiong, Leona Ting-Yuke Ho, Irwin Kee-Mun Cheah, Barry Halliwell, Deron R Herr, Wei-Yi Ong

Open access · bronzeAbstract read
In one paragraph

Article in Neuromolecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
8.7field-weighted citation impact, top 2% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

  1. Pooled it
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  4. King Oyster Mushroom,Nutrients · 2026
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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

9 authors at 2 institutions in 2 countries.

Sally Shuxian Koh *Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119260, Singapore.
Samantha Chia-Yi Ooi *Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119260, Singapore.
Natalie Man-Yin LuiDepartment of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119260, Singapore.
Cao QiongDepartment of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119260, Singapore.
Leona Ting-Yuke HoDepartment of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119260, Singapore.
Irwin Kee-Mun CheahNeurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore, 119260, Singapore.
Barry HalliwellNeurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore, 119260, Singapore.
Deron R HerrDepartment of Biology, San Diego State University, San Diego, CA, 92182, USA. dherr@sdsu.edu.ORCID 0000-0001-5755-0896
Wei-Yi OngDepartment of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119260, Singapore. antongwy@nus.edu.sg.
National University of Singapore · SGSan Diego State University · US

Funding

Ministry of Education (SG) R-181-000-183-114National University Health System NUHSRO/2019/051/T1/Seed-Mar/04
6 · The paper itself

Abstract

Ergothioneine (ET) is a naturally occurring antioxidant that is synthesized by non-yeast fungi and certain bacteria. ET is not synthesized by animals, including humans, but is avidly taken up from the diet, especially from mushrooms. In the current study, we elucidated the effect of ET on the hCMEC/D3 human brain endothelial cell line. Endothelial cells are exposed to high levels of the cholesterol oxidation product, 7-ketocholesterol (7KC), in patients with cardiovascular disease and diabetes, and this process is thought to mediate pathological inflammation. 7KC induces a dose-dependent loss of cell viability and an increase in apoptosis and necrosis in the endothelial cells. A relocalization of the tight junction proteins, zonula occludens-1 (ZO-1) and claudin-5, towards the nucleus of the cells was also observed. These effects were significantly attenuated by ET. In addition, 7KC induces marked increases in the mRNA expression of pro-inflammatory cytokines, IL-1β IL-6, IL-8, TNF-α and cyclooxygenase-2 (COX2), as well as COX2 enzymatic activity, and these were significantly reduced by ET. Moreover, the cytoprotective and anti-inflammatory effects of ET were significantly reduced by co-incubation with an inhibitor of the ET transporter, OCTN1 (VHCL). This shows that ET needs to enter the endothelial cells to have a protective effect and is unlikely to act via extracellular neutralizing of 7KC. The protective effect on inflammation in brain endothelial cells suggests that ET might be useful as a nutraceutical for the prevention or management of neurovascular diseases, such as stroke and vascular dementia. Moreover, the ability of ET to cross the blood-brain barrier could point to its usefulness in combatting 7KC that is produced in the CNS during neuroinflammation, e.g. after excitotoxicity, in chronic neurodegenerative diseases, and possibly COVID-19-related neurologic complications.

Indexed as

AntioxidantsApoptosisBiological TransportBlood-Brain BarrierBrainCell LineCholesterolClaudin-5COVID-19Cyclooxygenase 2CytokinesDrug Evaluation, PreclinicalEndothelial CellsErgothioneineHumansKetocholesterols7-ketocholesterolAntioxidantsCholesterolClaudin-5CLDN5 protein, humanCyclooxygenase 2CytokinesErgothioneineKetocholesterolsNeuroprotective AgentsNitric Oxide Synthase Type IINitric Oxide Synthase Type IIINOS2 protein, humanNOS3 protein, humanOrganic Cation Transport ProteinsPTGS2 protein, humanRNA, MessengerSLC22A4 protein, humanSymportersTJP1 protein, humanZonula Occludens-1 Protein7-ketocholesterolAnti-inflammatoryAntioxidantBlood–brain barrierClaudin-5CoronavirusCOVID-19COX2CyclooxygenaseCytokinesEicosanoidsErgothioneineFree radicalsInflammationMushroomsNF-kBOxidative stressOxysterolsTight junction proteinsTNF-αZO-1

Identifiers

PMID33067719
PMCPMC7567423
OpenAlexW3093361515

What OpenQuestion holds

Textmetadata
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.