Evidence map›Paper›PMID 26645674›Full record

ArticlePloS one2015

Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species.

Hengjie Yuan, Katie L Houck, Ye Tian, Uddalak Bharadwaj, Ken Hull, Zhou Zhou, Mingzhao Zhu, Mingzhao Zhou, Xiaoping Wu, David J Tweardy and 5 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. Extracellular Mitochondria Mediate Endothelial Injury After Traumatic Brain Injury.Arteriosclerosis, thrombosis, and vascular biology · 2026
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  5. The Antitumor Activity of Piplartine: A Review.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
  6. Review
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  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 3 countries.

Hengjie YuanBloodworks Northwest Research Institute, Seattle, Washington, United States of America.
Katie L HouckBloodworks Northwest Research Institute, Seattle, Washington, United States of America.
Ye TianBloodworks Northwest Research Institute, Seattle, Washington, United States of America.
Uddalak BharadwajDivision of Infectious Disease, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Ken HullThe Natural Products LINCHPIN Laboratory and Department of Chemistry, Texas A & M University, College Station, Texas, United States of America.
Zhou ZhouBloodworks Northwest Research Institute, Seattle, Washington, United States of America.
Mingzhao Zhu
Mingzhao ZhouThe Natural Products LINCHPIN Laboratory and Department of Chemistry, Texas A & M University, College Station, Texas, United States of America.
Xiaoping WuBloodworks Northwest Research Institute, Seattle, Washington, United States of America.
David J TweardyDivision of Infectious Disease, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Daniel RomoThe Natural Products LINCHPIN Laboratory and Department of Chemistry, Texas A & M University, College Station, Texas, United States of America.
Xiaoyun FuBloodworks Northwest Research Institute, Seattle, Washington, United States of America.
Yanjun ZhangMedicine Division, Imperial College London, London, United Kingdom.
Jianning ZhangTianjin Neurological Institute, General Hospital, Tianjin Medical University, Tianjin, China.
Jing-fei DongBloodworks Northwest Research Institute, Seattle, Washington, United States of America.
Bloodworks Northwest · USTexas A&M University · USBaylor College of Medicine · USTianjin Medical University General Hospital · CNImperial College London · GBUniversity of Washington · US

Funding

Ultra-Large VWF and Thrombotic MicroangiopathyR01HL071895 · NHLBI · BLOODWORKS · PI DONG, JING-FEI · 2003 to 2012
$3.4M
Proteolysis of ultralarge von Willebrand factor and metabolic syndrome-diabetesR01HL085769 · NHLBI · BLOODWORKS · PI DONG, JING-FEI · 2008 to 2011
$1.5M
Stat3 Probes that Target Breast Cancer Stem CellsR21CA149783 · NCI · BAYLOR COLLEGE OF MEDICINE · PI TWEARDY, DAVID JOHN · 2010 to 2011
$362k
NCI NIH HHS CA149783NCI NIH HHS R21 CA149783NHLBI NIH HHS HL085769NHLBI NIH HHS HL71895NHLBI NIH HHS R01 HL071895NHLBI NIH HHS R01 HL085769
6 · The paper itself

Abstract

backgroundPiperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known.

objectiveWe conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen.

resultsPL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect.

conclusionsPL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals.

Indexed as

CollagenDioxolanesHumansJanus Kinase 2PiperidonesPlatelet ActivationPlatelet AggregationReactive Oxygen SpeciesSTAT3 Transcription FactorCollagenDioxolanesJAK2 protein, humanJanus Kinase 2PiperidonespiperlongumineReactive Oxygen SpeciesSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID26645674
PMCPMC4672935
OpenAlexW2194454497

What OpenQuestion holds

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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.