Evidence map›Paper›PMID 30237488›Full record

ArticleNature communications2018

Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase.

Helmut Pein, Alexia Ville, Simona Pace, Veronika Temml, Ulrike Garscha, Martin Raasch, Khaled Alsabil, Guillaume Viault, Chau-Phi Dinh, David Guilet and 21 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
7.7field-weighted citation impact, top 1% 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

71 citing papers in PubMed, 145 citations in OpenAlex.

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  15. Investigating the role of the mPGES-PGE₂-EP4 pathway inFrontiers in veterinary science · 2025
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11 more citing papers are in PubMed but not listed here.

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

31 authors at 6 institutions in 4 countries.

Helmut PeinChair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743, Jena, Germany.
Alexia VilleSubstances d'Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire, 49070, Beaucouzé, France.
Simona PaceChair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743, Jena, Germany.
Veronika TemmlInstitute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020, Innsbruck, Austria.
Ulrike GarschaChair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743, Jena, Germany.
Martin RaaschInstitute of Biochemistry II and Center for Sepsis Control and Care, University Hospital Jena, 07743, Jena, Germany.
Khaled AlsabilSubstances d'Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire, 49070, Beaucouzé, France.
Guillaume ViaultSubstances d'Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire, 49070, Beaucouzé, France.
Chau-Phi DinhSubstances d'Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire, 49070, Beaucouzé, France.
David GuiletSubstances d'Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire, 49070, Beaucouzé, France.
Fabiana TroisiChair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743, Jena, Germany.
Konstantin NeukirchChair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743, Jena, Germany.
Stefanie KönigChair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743, Jena, Germany.
Rosella BilanciaDepartment of Pharmacy, School of Medicine, University of Naples Federico II, 80131, Naples, Italy.
Birgit WaltenbergerInstitute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020, Innsbruck, Austria.
Hermann StuppnerInstitute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020, Innsbruck, Austria.
Maria WallertChair of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich-Schiller-University Jena, 07743, Jena, Germany.
Stefan LorkowskiChair of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich-Schiller-University Jena, 07743, Jena, Germany.
Christina WeinigelInstitute of Transfusion Medicine, University Hospital Jena, 07747, Jena, Germany.
Silke RummlerInstitute of Transfusion Medicine, University Hospital Jena, 07747, Jena, Germany.
Marc BirringerDepartment of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, 36037, Fulda, Germany.
Fiorentina RoviezzoDepartment of Pharmacy, School of Medicine, University of Naples Federico II, 80131, Naples, Italy.
Lidia SautebinDepartment of Pharmacy, School of Medicine, University of Naples Federico II, 80131, Naples, Italy.
Jean-Jacques HelesbeuxSubstances d'Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire, 49070, Beaucouzé, France.
Denis SéraphinSubstances d'Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire, 49070, Beaucouzé, France.
Alexander S MosigInstitute of Biochemistry II and Center for Sepsis Control and Care, University Hospital Jena, 07743, Jena, Germany.ORCID http://orcid.org/0000-0002-5687-2444
Daniela SchusterInstitute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020, Innsbruck, Austria.
Antonietta RossiDepartment of Pharmacy, School of Medicine, University of Naples Federico II, 80131, Naples, Italy.
Pascal RichommeSubstances d'Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire, 49070, Beaucouzé, France.
Oliver WerzChair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743, Jena, Germany. oliver.werz@uni-jena.de.
Andreas KoeberleChair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743, Jena, Germany. andreas.koeberle@uni-jena.de.ORCID http://orcid.org/0000-0001-6269-5088
Friedrich Schiller University Jena · DEUniversité Bretagne Loire · FRJena University Hospital · DEUniversität Innsbruck · ATUniversity of Naples Federico II · ITFulda University of Applied Sciences · DE

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01EA1411ABundesministerium für Wirtschaft und Technologie (Federal Ministry of Economics and Technology) AiF 16642 BRDeutsche Forschungsgemeinschaft (German Research Foundation) GA 2101/2-1Deutsche Forschungsgemeinschaft (German Research Foundation) GRK 1715Deutsche Forschungsgemeinschaft (German Research Foundation) KO 4589/7-1Deutsche Forschungsgemeinschaft (German Research Foundation) RTG 1715Deutsche Forschungsgemeinschaft (German Research Foundation) SFB1127Deutsche Forschungsgemeinschaft (German Research Foundation) SFB1278Deutscher Akademischer Austauschdienst (German Academic Exchange Service) 57389523
6 · The paper itself

Abstract

Systemic vitamin E metabolites have been proposed as signaling molecules, but their physiological role is unknown. Here we show, by library screening of potential human vitamin E metabolites, that long-chain ω-carboxylates are potent allosteric inhibitors of 5-lipoxygenase, a key enzyme in the biosynthesis of chemoattractant and vasoactive leukotrienes. 13-((2R)-6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid (α-T-13'-COOH) can be synthesized from α-tocopherol in a human liver-on-chip, and is detected in human and mouse plasma at concentrations (8-49 nM) that inhibit 5-lipoxygenase in human leukocytes. α-T-13'-COOH accumulates in immune cells and inflamed murine exudates, selectively inhibits the biosynthesis of 5-lipoxygenase-derived lipid mediators in vitro and in vivo, and efficiently suppresses inflammation and bronchial hyper-reactivity in mouse models of peritonitis and asthma. Together, our data suggest that the immune regulatory and anti-inflammatory functions of α-tocopherol depend on its endogenous metabolite α-T-13'-COOH, potentially through inhibiting 5-lipoxygenase in immune cells.

Indexed as

AdolescentAdultAgedAnimalsArachidonate 5-LipoxygenaseBronchial HyperreactivityCell-Free SystemCell SurvivalHumansInflammationInhibitory Concentration 50LeukocytesLipoxygenase InhibitorsLiverMetabolomeMiceArachidonate 5-LipoxygenaseLipoxygenase InhibitorsRecombinant ProteinsVitamin E

Identifiers

PMID30237488
PMCPMC6148290
OpenAlexW2891206452

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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.