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Enhancing the biological activity of polyphenols based on understanding their chemistry

Aguilar-Carrillo AB, Garduño-Valdovinos SA, Nava GM, Sánchez-Quezada V, Madrigal-Perez LA

2026

Abstract

Polyphenols are compounds synthesized by plants as part of their chemical defense system to counteract biotic and abiotic stressors. These compounds share two key chemical characteristics: their aromatic groups make them insoluble in water, while hydroxy groups provide redox properties. These characteristics may explain how polyphenols interact with mitochondrial membranes (which are lipophilic) and participate in redox (electron scavenging) reactions of the electron transport chain, ultimately affecting ATP synthesis via oxidative phosphorylation. This interaction accounts for both the beneficial and adverse effects of polyphenols. However, no research has examined how hydroxyl groups or a lipophilic environment influence the biological activity of polyphenols. Therefore, this study aimed to explore the impact of hydroxy groups and a lipophilic environment on the biological activity of polyphenols. We tested four polyphenols (quercetin, naringenin, resveratrol, and gallic acid) with varying numbers of hydroxyl and other functional groups to determine how hydroxyl groups affect their biological activity (toxicity) in Saccharomyces cerevisiae . Additionally, we evaluated different fatty acids to understand how a lipophilic environment influences polyphenol biological activity. The results of this study support the two main ideas of our hypothesis: 1) a lipid solvent increases the toxicity of polyphenols, and 2) the molecule with the most hydroxyl groups is the most toxic (as…

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