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Chemobrain as a Neuroimmune Syndrome: Mechanisms, Modifiers, and Emerging Multi-Target Therapeutic Strategies
Federica Carnemolla1, Sandeep Kumar Singh2, Leonardo Ceccherini1
1Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy.
Molecules (Basel, Switzerland)
|June 12, 2026
Summary
Dietary phenolic compounds may help mitigate chemotherapy-induced cognitive impairment (CICI), or "chemobrain," by targeting neurotoxic pathways. Further research is needed to confirm their efficacy in humans, especially for at-risk populations.
Area of Science:
- Neuroscience
- Pharmacology
- Nutritional Science
Background:
- Chemotherapy-induced cognitive impairment (CICI), or "chemobrain," is a prevalent neurotoxic side effect of cancer treatment.
- CICI manifests as deficits in memory, attention, and executive function, disproportionately affecting older adults and women.
- Aging and estrogen depletion are implicated in CICI vulnerability.
Purpose of the Study:
- To investigate the potential of dietary phenolic compounds in modulating CICI mechanisms.
- To synthesize preclinical and clinical evidence on phenolic compounds' effects on neurotoxicity pathways.
Main Methods:
- A narrative synthesis approach was employed.
- Reviewed evidence focused on major phenolic subclasses (flavonoids, phenolic acids, stilbenes, lignans, secoiridoids).
- Examined effects on pathways including redox balance, neuroinflammation, mitochondrial function, synaptic plasticity, and estrogen signaling.
Main Results:
- Phenolic compounds demonstrated potential to influence multiple pathways implicated in CICI.
- Effects appear structure-dependent, with significant heterogeneity in evidence.
- Most evidence originates from experimental models, with limited human data.
Conclusions:
- Selected dietary phenolic compounds may offer a safe, adjunctive strategy to mitigate CICI risk, particularly in older adults and women with low estrogen.
- Further rigorous clinical studies are essential to validate efficacy and elucidate mechanisms of action.
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