Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis-A Systematic Review

Area of Science:

• Biochemistry and Molecular Biology
• Cell Biology
• Pharmacology

Background:

• Ferroptosis is a distinct form of programmed cell death characterized by iron accumulation, reactive oxygen species, glutathione depletion, and lipid peroxidation.
• Ferroptosis is implicated in various diseases, including neurodegenerative disorders, ischemia/reperfusion injury, cancer, and chronic kidney disease.
• Polyphenols, plant-derived compounds with diverse bioactivities, are increasingly studied for their role in modulating ferroptosis.

Purpose of the Study:

• To systematically review the literature on the influence of polyphenols on ferroptosis.
• To identify phenolic compounds that can induce or inhibit ferroptosis and elucidate their mechanisms of action.

Main Methods:

• An extensive literature search was conducted across Scopus, Web of Science, PubMed, ScienceDirect, and Springer from 2017 to November 2023.
• Keywords included 'ferroptosis' combined with various polyphenol classes (flavonoid, phenolic acid, stilbene, coumarin, anthraquinone, chalcone).
• 311 papers and 143 phenolic compounds were analyzed.

Main Results:

• Out of 143 phenolic compounds, 53 were found to induce ferroptosis, and 110 inhibited it.
• Twenty compounds demonstrated dual ability to induce and inhibit ferroptosis, depending on the experimental system.
• Shikonin, curcumin, quercetin, resveratrol, and baicalin were the most frequently researched compounds.

Conclusions:

• Polyphenols exhibit significant potential in modulating ferroptosis, with many compounds capable of inducing or inhibiting this cell death pathway.
• Common mechanisms involve the modulation of the Nrf2/GPX4 and Nrf2/HO-1 axes, as well as iron metabolism.
• These findings highlight polyphenols as promising candidates for therapeutic strategies targeting ferroptosis-related diseases.