Liquiritin enhancing intestinal absorption of paeoniflorin in in situ single-pass intestinal perfusion and in vitro Caco-2 cell monolayer absorption models

Background: Paeoniflorin and liquiritin are the primary active components of Shaoyao-Gancao-tang (SGT), a classical prescription for reducing pains. However, the interaction of paeoniflorin and liquiritin during intestinal absorption needs to be further studied. Objectives: In this study, we aimed to determine the interaction of paeoniflorin and liquiritin during intestinal absorption. Materials and Methods: The interaction between paeoniflorin and liquiritin (100 μM) was studied using in situ single-pass intestinal perfusion (SPIP) model use the whole small intestine and in vitro Caco-2 cell monolayer bidirectional transport model. Results: In situ SPIP research demonstrated that liquiritin significantly increased the K_a, P_app, absorption rate, and cumulative amount of paeoniflorin up to 7.97, 8.98, 7.07, and 10.71 folds, respectively, even higher than that of verapamil, a specific P-gp inhibitor, and control. Furthermore, 18 β-glycyrrhetinic acid (18 β-GA) markedly increased the K_a, P_app, absorption rate, and cumulative amount of paeoniflorin up to 3.30, 3.27, 3.42, and 4.04 folds, respectively. Bidirectional transport studies indicated that liquiritin and paeoniflorin could prompt the absorption of each other by increasing the P_{app (AP-BL)} of paeoniflorin and liquiritin from (3.83 ± 0.51) ×10⁻⁷ to (5.60 ± 0.51) ×10⁻⁷ cm/s and (3.86 ± 0.34) ×10⁻⁷ to (8.26 ± 0.51) ×10⁻⁷ cm/s, respectively. The 18 β-GA significantly prompted the P_{app (AP-BL)} of paeoniflorin to (5.54 ± 0.92) ×10⁻⁷ cm/s. Conclusion: Liquiritin and paeoniflorin increased the absorption of each other. This could provide essential reference to predict the oral bioavailability, the pharmacokinetics, and the clinical application of coadministration of liquiritin-and paeoniflorin-containing SGT and other herbal formulas.