Evidence map›Paper›PMID 26134265›Full record

ArticleToxicology and applied pharmacology2015

Thymoquinone inhibits TNF-α-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation.

Sadiq Umar, Omar Hedaya, Anil K Singh, Salahuddin Ahmed

Abstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
20.7field-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

52 citing papers in PubMed, 103 citations in OpenAlex.

  1. Effect ofF1000Research · 2021
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  2. Foods (Basel, Switzerland) · 2026
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  14. Laryngoscope investigative otolaryngology · 2023
    Article
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  18. Review
  19. OralPharmaceutics · 2022
    Article
  20. Article
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 1 institution in 1 country.

Sadiq UmarDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA, USA.
Omar HedayaDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA, USA.
Anil K SinghDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA, USA.
Salahuddin AhmedDepartment of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA, USA. Electronic address: salah.ahmed@wsu.edu.
Washington State University Spokane · US

Funding

Regulation of IL-6 mediated inflammation and tissue destruction by EGCGR01AR063104 · NIAMS · WASHINGTON STATE UNIVERSITY · PI AHMED, SALAH-UDDIN · 2013 to 2017
$1.7M
NIAMS NIH HHS AR063104NIAMS NIH HHS R01 AR063104
6 · The paper itself

Abstract

Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine produced by monocytes/macrophage that plays a pathological role in rheumatoid arthritis (RA). In this study, we investigate the effect of thymoquinone (TQ), a phytochemical found in Nigella sativa, in regulating TNF-α-induced RA synovial fibroblast (RA-FLS) activation. Treatment with TQ (1-5μM) had no marked effect on the viability of human RA-FLS. Pre-treatment of TQ inhibited TNF-α-induced interleukin-6 (IL-6) and IL-8 production and ICAM-1, VCAM-1, and cadherin-11 (Cad-11) expression in RA-FLS (p<0.01). Evaluation of the signaling events showed that TQ inhibited TNF-α-induced phospho-p38 and phospho-JNK expression, but had no inhibitory effect on NF-κB pathway, in RA-FLS (p<0.05; n=4). Interestingly, we observed that selective down-regulation of TNF-α-induced phospho-p38 and phospho-JNK activation by TQ is elicited through inhibition of apoptosis-regulated signaling kinase 1 (ASK1). Furthermore, TNF-α selectively induced phosphorylation of ASK1 at Thr845 residue in RA-FLS, which was inhibited by TQ pretreatment in a dose dependent manner (p<0.01). Pre-treatment of RA-FLS with ASK1 inhibitor (TC ASK10), blocked TNF-α induced expression of ICAM-1, VCAM-1, and Cad-11. Our results suggest that TNF-α-induced ASK1-p38/JNK pathway is an important mediator of cytokine synthesis and enhanced expression of adhesion molecule in RA-FLS and TQ, by selectively inhibiting this pathway, may have a potential therapeutic value in regulating tissue destruction observed in RA.

Indexed as

Anti-Inflammatory AgentsArthritis, RheumatoidBenzoquinonesCell AdhesionCell Adhesion MoleculesCells, CulturedDose-Response Relationship, DrugEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFibroblastsHumansInflammation MediatorsInterleukin-6Interleukin-8MAP Kinase Kinase Kinase 5p38 Mitogen-Activated Protein KinasesAnti-Inflammatory AgentsBenzoquinonesCell Adhesion MoleculesCXCL8 protein, humanExtracellular Signal-Regulated MAP KinasesIL6 protein, humanInflammation MediatorsInterleukin-6Interleukin-8MAP3K5 protein, humanMAP Kinase Kinase Kinase 5p38 Mitogen-Activated Protein KinasesthymoquinoneTumor Necrosis Factor-alphaASK1MAP kinaseRheumatoid arthritisSynovial fibroblastsThymoquinoneTNF-α

Identifiers

PMID26134265
PMCPMC4549173
OpenAlexW755401697

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.