Cellular Transport of Esculin and Its Acylated Derivatives in Caco-2 Cell Monolayers and Their Antioxidant Properties in Vitro.

Esculin has many pharmacological effects, but these are difficult to observe after oral administration owing to poor lipid solubility. In our previous study, five acylated derivatives with different acyl chain lengths (EA, EP, EO, EL, and EM) were synthesized to improve the lipophilicity of esculin. In this study, the bioavailability and antioxidant activity of the five derivatives were investigated. The logP of esculin, EA, EP, EO, EL, and EM were -1.1 ± 0.1, -0.3 ± 0.14, 0.1 ± 0.17, 1.6 ± 0.09, 2.4 ± 0.11, and 2.8 ± 0.18, and their Papp were 0.71 ± 0.02, 1.24 ± 0.18, 1.74 ± 0.11, 11.6 ± 3.6, 4.11 ± 1.03, and 2.64 ± 0.97 × 10-6 cm/s, respectively. Besides, the bioavailability of EO, EL, and EM were seriously affected by carboxylesterase. The results of ABTS, ORAC, and DPPH assays indicated that the antiradical ability of the five derivatives did not exceed that of esculin. However, EA, EP, and EO showed more effective inhibition of AAPH-induced oxidative hemolysis than esculin did (p < 0.05), and EL and EM were less effective than esculin (p < 0.05). The mechanism was related to the distribution and localization of the derivatives in "oil-water interface" between the cytomembrane and the aqueous phase.