Chromatographic separation of strawberry polyphenols identified pelargonidin as the primary, active permeation enhancer. (A) Of 22 fractions that resulted from MPLC separations of strawberry polyphenols, only the ε3 fraction enhanced the permeability of Caco-2 monolayers. “+” denotes fractions that were too small to examine at the otherwise standardized concentration of 1 mg/mL. (B) Similarly, of a large group of commercially purchased phenolic compounds known to occur in strawberries, only the pigment molecule pelargonidin significantly increased the permeability of calcein across cell monolayers. (C) Chemical structure of pelargonidin. (D) Pelargonidin permeabilized intestinal Caco-2 cells, as measured by TEER, and (E) improved calcein permeability in a dose-dependent manner. Error bars represent SEM (n = 3 or 4 replicate wells).