Evidence map›Paper›PMID 41498012›Full record

ReviewOxidative medicine and cellular longevity2025

Targeting NRF2 With Isoeugenol: A Promising Small Molecule for Neurodegenerative, Metabolic, and Chronic Inflammatory Disorders.

Ana Silva, Sónia Silva, Beatriz Rodrigues, Gonçalo Simões, Inês Dinis, Mafalda Freitas, Rosa Resende, Joana Bicker, Ana Fortuna, Maria M Silva and 5 more

Abstract readReview
In one paragraph

Review in Oxidative medicine and cellular longevity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Intranasal Administration of Isoeugenol Improves Memory Deficits in APP/PS1 Old Mice-A Role Beyond Nrf2 Activation?FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  2. Review
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

15 authors.

Ana SilvaCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0002-4041-0376
Sónia SilvaCNC, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0001-9869-8651
Beatriz RodriguesCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0009-0008-2613-744X
Gonçalo SimõesCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0009-0007-3121-8466
Inês DinisCNC, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.
Mafalda FreitasCNC, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.
Rosa ResendeCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0002-0504-5756
Joana BickerCNC, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0001-7500-1671
Ana FortunaCNC, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0001-6981-6639
Maria M SilvaCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0002-1938-4150
Armanda E SantosCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0003-1111-2481
Sónia A PinhoCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0002-7426-5197
Bruno NevesiBiMED, Department of Medical Sciences and Institute of Biomedicine, University of Aveiro, Aveiro, 3810-193, Portugal, ua.pt.ORCID 0000-0001-7391-3124
Cláudia Fragão PereiraCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0002-6630-5056
Maria Teresa CruzCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3000-548, Portugal, uc.pt.ORCID 0000-0001-9846-6754

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Oxidative stress, driven by an imbalance between oxidants and antioxidants, disrupts redox homeostasis and contributes to the development of chronic diseases, including cancer, diabetes, neurodegenerative disorders, and aging. The NRF2-KEAP1 pathway is a pivotal cellular defense mechanism against oxidative stress, regulating the transcription of cytoprotective genes. Pharmacological NRF2 activation has emerged as a promising strategy to mitigate oxidative stress-related pathologies; however, challenges regarding target specificity, pharmacodynamics, efficacy, and safety remain unresolved. Isoeugenol, a phenylpropanoid found in essential oils, has traditionally been recognized as a skin allergen but is now gaining attention for its potential as an NRF2 activator. Emerging evidence suggests that isoeugenol exerts antioxidant, anti-inflammatory, and neuroprotective effects and modulates metabolic disorders such as diabetes mellitus. Despite its therapeutic potential, the direct correlation between isoeugenol's effects and NRF2 activation remains underexplored. Existing studies indicate that isoeugenol may activate NRF2 through multiple mechanisms, including covalent modification of KEAP1 cysteine residues, increased AKT activation and GSK3β inactivation, and glutathione depletion leading to reactive oxygen species (ROS) generation. Understanding these activation pathways is critical for leveraging isoeugenol as a therapeutic agent. This review provides a comprehensive analysis of isoeugenol's role in modulating NRF2 activity and its implications for treating oxidative stress-driven diseases. By integrating current findings, this review highlights new insights into the therapeutic potential of isoeugenol in translational medicine. We propose future research directions to optimize its application in clinical settings, paving the way for more targeted and effective NRF2-based interventions in chronic disease management.

Indexed as

EugenolInflammationMetabolic DiseasesNeurodegenerative DiseasesNF-E2-Related Factor 2AnimalsChronic DiseaseHumansOxidative StressEugenolisoeugenolNF-E2-Related Factor 2Alzheimer’s diseasediabetesinflammationisoeugenolNRF2skin allergen

Identifiers

PMID41498012
PMCPMC12767388

What Socratic holds

Textmetadata
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 Socratic graph.