Phytochemicals as modulators of ferroptosis: a novel therapeutic avenue in cancer and neurodegeneration.

Publication date: Jun 25, 2025

Ferroptosis, a controlled cell death mechanism characterised by iron-dependent lipid peroxidation, has become a significant factor in the pathophysiology of cancer and neurodegenerative disorders. Its dual role as a tumor suppressor and mediator of neuronal damage highlights its significance as a therapeutic target. Phytochemicals, natural bioactive molecules in plants, have attracted interest for their ability to modulate ferroptosis through diverse mechanisms, including regulation of oxidative stress, iron metabolism, and antioxidant defense systems. This review examines the complex relationship between ferroptosis and disease mechanisms, emphasizing its relevance in treatment-resistant cancers and neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Information was taken from reputable databases such as PubMed, Scopus, and Web of Science. We thoroughly analyzed the current evidence on phytochemicals-including polyphenols like curcumin and epigallocatechin gallate, flavonoids like quercetin and luteolin, and alkaloids like berberine-as modulators of ferroptotic pathways. Despite their promising therapeutic potential, challenges such as limited bioavailability, pharmacokinetics, and clinical validation remain significant hurdles. Future research focusing on advanced delivery systems, synergistic approaches, and personalized medicine strategies could unlock the full potential of phytochemicals in ferroptosis-targeted therapies. This review underscores phytochemicals as a novel and versatile avenue in addressing the unmet therapeutic needs in cancer and neurodegenerative diseases.

Concepts Keywords
Cancers Animals
Hurdles Antioxidants
Parkinson Antioxidants
Pathophysiology Cancer
Pharmacokinetics Catechin
Catechin
epigallocatechin gallate
Ferroptosis
Ferroptosis
Humans
Iron
Iron
Iron overload
Lipid Peroxidation
Lipid peroxidation
Neoplasms
Neurodegenerative Diseases
Neurodegenerative diseases
Oxidative Stress
Phytochemicals
Phytochemicals
Phytochemicals

Semantics

Type Source Name
pathway KEGG Ferroptosis
disease MESH cancer
drug DRUGBANK Iron
disease MESH neurodegenerative disorders
disease MESH oxidative stress
pathway REACTOME Metabolism
drug DRUGBANK Curcumin
drug DRUGBANK Epigallocatechin gallate
drug DRUGBANK Quercetin
drug DRUGBANK Berberine
pathway REACTOME Neurodegenerative Diseases
drug DRUGBANK Cianidanol
disease MESH Iron overload

Original Article

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