Bee Pollen Potential to Modulate Ferroptosis: Phytochemical Insights for Age-Related Diseases.

Bee pollen (BP) is one of the richest known natural resources of micronutrients and bioactive phytochemicals. Some captivating bioactivities of BP compounds, although being largely investigated for the latter as individual molecules, remain very scarcely investigated or completely uninvestigated in bee pollen as a whole product. Among the most intriguing of these bioactivities, we identified ferroptosis as a major one. Ferroptosis, a recently discovered form of cell death (connecting oxidative stress and inflammation), is a complex pathophysiological process and one of the most crucial and perplexing events in current challenging human diseases such as cancer, neurodegeneration, and general aging diseases. Many BP compounds were found to intricately modulate ferroptosis depending on the cellular context by inducing this cell death mechanism in malignant cells and preventing it in non-malignant cells. Since research in both fields, i.e., BP and ferroptosis, is still recent, we deemed it necessary to undertake this review to figure out the extent of BP potential in modulating ferroptosis mechanisms. Our research proved that a wide range of BP compounds (polyphenols, phenolamides, carotenoids, vitamins, minerals, and others) substantially modulate diverse ferroptosis mechanisms. Accordingly, these phytochemicals and nutrients showed interesting potential in preclinical studies to lead to ferroptosis-mediated outcomes in important pathophysiological processes, including many aging-related disorders. One of the most paramount challenges that remain to be resolved is to determine how different BP compounds act on ferroptosis in different biological and pathophysiological contexts, either through synergistic or antagonistic behaviors. We hope that our current work constitutes a valuable incentive for future investigations in this promising and very relevant research avenue.