Research on intestinal permeability of glycyrrhetinic acid in multicomponent environment / 中草药

ABSTRACT

Objective: To investigate the characteristics of intestinal absorption of glycyrrhetinic acid in rats in the multicomponent environment. Methods: The effect of multicomponent environment on intestinal absorption of glycyrrhetinic acid was investigated in rat model of in situ single-pass intestinal perfusion, HPLC was used to determine the concentration of glycyrrhetinic acid in intestinal perfusion fluid samples, the effective permeability coefficient (Peff), absorption rate constant (Ka), and absorption fraction (Fa) of glycyrrhetinic acid in rats ileum were calculated, the effects of glycyrrhetinic acid with different mass concentration and P-glycoprotein (P-gp) inhibitor verapamil, as well as the compatibility of different components on intestinal absorption of glycyrrhetinic acid were examined,. Results: The Peff, Ka, and Fa values of glycyrrhetinic acid perfusion liquid (10 and 20 µg/mL) in the ileum segment had no significant difference. Added with 100 µmol/L verapamil, Peff, and Fa values of 10 µg/mL glycyrrhetinic acid increased, which illustrated that the glycyrrhetinic acid might be the substrate of P-gp; In two components compatibility, the effect of baicalin on absorption of glycyrrhetinic acid was the most obvious, Peff value of glycyrrhetinic acid was from (4.05 ± 0.78) × 10-5 cm/s to (2.18 ± 0.63) × 10-5 cm/s, and the penetration of glycyrrhetinic acid was reduced. The puerarin consociation baicalin and berberine had no obvious effect on permeability of glycyrrhetinic acid. In the three components compatibility condition, the experimental results showed that after glycyrrhetinic acid combined with puerarin and berberine, the permeability coefficient did not change, while the permeability coefficient changed, but not obviously, glycyrrhetinic acid combined with baicalin and berberine had lower permeability, Peff values were from (4.05 ± 0.78) × 10-5 cm/s down to (1.35 ± 0.69) × 10-5 cm/s, and the effects of baicalin on glycyrrhetinic acid was evident. Conclusion: Glycyrrhetinic acid can be absorbed in the ileum of rats, and has no obvious influence on Peff and Ka values within a certain range of quality concentration. The absorption mechanism is determined to be passive diffusion, glycyrrhetinic acid is substrate of P-gp, and saturation phenomenon exists transporters; Baicalin has significant effects on glycyrrhetinic acid absorption, which may be related to the induction by P-pg expression, increasing the glycyrrhetinic acid from cell to the extracellular discharge, reducing the penetration of glycyrrhetinic acid, and influencing the absorption.