Exploring absorption indices for a variety of polyphenols through Caco-2 cell model: insights from permeability studies and principal component analysis

Abstract

BACKGROUND: Phytochemicals have long been utilized as active ingredients in the developing of novel functional foods or drugs due to their diverse biological and pharmacological effects. Many studies have demonstrated that polyphenols exhibit low absorption rates and are extensively metabolized into various metabolites, resulting in significantly reduced bioavailability. RESULTS: Puerarin and diosmin exhibited the highest transport from the apical (AP) to basolateral (BL) direction, while diosmin and silybin showed the highest BL to AP transport. Most polyphenols demonstrated well-absorbed characteristics based on their apparent permeability coefficients (P-app), except for flavokawain A, phloretin, chrysin and dicoumarol, which displayed incomplete bidirectional absorption. Hesperetin exhibited a notable efflux ratio (ER) of 5.45, suggesting increased efflux compared to other compounds. A strong positive correlation was observed for P-app in both directions (Pearson correlation coefficient (PCC) = 0.53, P < 0.001), with a moderate correlation between ER and P-app(BL -> AP) (PCC = 0.49, P < 0.001). Principal component analysis highlighted P-app(BL -> AP) as the most influential indicator for polyphenol permeability, explaining a relatively wide portion of the data variance. Polyphenol compounds with a higher number of functional groups, such as -OH and -CH3, exhibited enhanced absorption due to increased binding affinity with intestinal cells and interactions with intracellular proteins. CONCLUSION: These findings offer valuable insights for expressing polyphenol permeability via Caco-2 cells and may contribute to strategies aimed at enhancing the biological activities of polyphenols. (c) 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.