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November 29, 2018MetabolitesOpen Access

Urolithin A Is a Dietary Microbiota-Derived Human Aryl Hydrocarbon Receptor Antagonist

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Key result

Urolithin A attenuates AHR-mediated inflammatory signaling in vitro as a direct human-selective antagonist.

  • P<0.0001

Why the study?

The molecular mechanisms underlying the beneficial effects of urolithins, including their anti-inflammatory and anti-cancer effects, remain unclear.

Population

Caco-2 cells and cell-based reporter systems

Comparison

Urolithin A and B vs TCDD or control

Design

Preclinical cell-based experimental study

Authors

GMGulsum E. MukuIMIain A. MurrayJEJuan Carlos Espı́n

Discussion

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Overview

May inform AHR-targeted anti-inflammatory strategies; leaves open translation to human cardiovascular disease.

Structured PICO

P
Population
Caco-2 cells and cell-based reporter systems
I
Intervention
Urolithin A (UroA) and Urolithin B (UroB)
C
Comparator
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) or control
O
Outcome
AHR-mediated transcriptional activity and CYP1A1 mRNA levelssurrogate

Main Result

p-value: p=<0.0001

Urolithin A is identified as a dietary microbiota-derived human selective AHR antagonist, providing a molecular mechanism for its anti-inflammatory effects.

Limitations

  • In vitro study design
  • Clinical relevance and in vivo effects require further investigation

Cite This Study

Muku et al. (2018) studied this question. Urolithin A vs. Vehicle or TCDD alone was evaluated on AHR-mediated transcriptional activity and CYP1A1 mRNA levels (p=<0.0001). Urolithin A acts as a direct, human-selective aryl hydrocarbon receptor antagonist that attenuates TCDD-induced AHR-mediated transcriptional activity and inflammatory signaling in vitro.

synapsesocial.com/papers/6aadef4f0adfe422ba183502https://doi.org/10.3390/metabo8040086
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Also Consider

Synapse has enriched 2 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1The Uremic Toxin 3-Indoxyl Sulfate Is a Potent Endogenous Agonist for the Human Aryl Hydrocarbon Receptor2009 · 311 citations
  2. 2Aryl Hydrocarbon Receptor Activation Synergistically Induces Lipopolysaccharide-Mediated Expression of Proinflammatory Chemokine (c–c motif) Ligand 202015 · 36 citations