Absorption and Interaction of the Main Constituents from the Traditional Chinese Drug Pair Shaoyao-Gancao via a Caco-2 Cell Monolayer Model

Shaoyao-Gancao (Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma) is a traditional Chinese drug pair widely used in decoctions for relieving pains, especially abdominal pain. We aimed to determine the intestinal absorption and interaction of three active compounds (glycyrrhizic acid, liquiritin, and paeoniflorin) in this drug pair. We investigated the transport of these compounds across intestinal epithelial cells by using the Caco-2 cell monolayer in both the apical-to-basolateral (A-B) and B-A directions. All compounds could only travel through the Caco-2 cell monolayer at a low level when the cells were treated with single component solutions. In the presence of verapamil, an inhibitor of P-glycoprotein (P-gp), the absorptive permeability (P(AB)) of paeoniflorin and liquiritin increased significantly (p < 0.05) and efflux ratios decreased, while the absorption of glycyrrhizic acid did not change significantly, which indicated that paeoniflorin and liquiritin might be P-gp substrates. In addition, when liquiritin and glycyrrhizic acid in Gancao extract and paeoniflorin in Shaoyao extract were examined, P(AB) of paeoniflorin and liquiritin were significantly higher, while glycyrrhizic acid retained the same absorption level compared to the corresponding single component solutions, which suggested that some certain ingredients in the extracts can promote the absorption of paeoniflorin and liquiritin, but not that of glycyrrhizic acid. Furthermore, compared to the results of treatment with individual extracts, treatment of cells with a mixture of the two extracts considerably increased (p < 0.05) the absorption of glycyrrhizic acid and paeoniflorin and showed no change in the absorption of liquiritin, which implied that the transport of glycyrrhizic acid and paeoniflorin is increased by some ingredients from the complementary drug in the drug pair, while that of liquiritin remains unaffected.