Acteoside and salidroside are major phenylethanoid glycosides (PhGs) in Osmanthus fragrans Lour. flowers with extensive pharmacological activities and poor oral bioavailability. The absorption mechanisms of these two compounds remain unclear. This study aimed to investigate the bioaccessibility of these compounds using an in vitro gastrointestinal digestion model and to examine the absorption and transport mechanisms of PhGs using the Caco-2 cell model. The in vitro digestion model revealed that the bioaccessibility of salidroside (98.7 ± 1.35%) was higher than that of acteoside (50.1 ± 3.04%), and the superior bioaccessibility of salidroside can be attributed to its stability. The absorption percentages of total phenylethanoid glycoside, salidroside, and acteoside were 1.42-1.54%, 2.10-2.68%, and 0.461-0.698% in the Caco-2 model, respectively. Salidroside permeated Caco-2 cell monolayers through passive diffusion. At the concentration of 200 μg/mL, the apparent permeability ( Papp) of salidroside in the basolateral (BL)-to-apical (AP) direction was 23.7 ± 1.33 × 10-7 cm/s, which was 1.09-fold of that in the AP-to-BL direction (21.7 ± 1.38 × 10-7 cm/s). Acteoside was poorly absorbed with low Papp (AP to BL) (4.75 ± 0.251 × 10-7 cm/s), and its permeation mechanism was passive diffusion with active efflux mediated by P-glycoprotein (P-gp). This study clarified the bioaccessibility, absorption, and transport mechanisms of PhGs. It also demonstrated that the low bioavailability of acteoside might be attributed to its poor bioaccessibility, low absorption, and P-gp efflux transporter.
Keywords: absorption mechanism; acteoside; bioaccessibility; salidroside; total phenylethanoid glycoside.