Assessment of intestinal absorption of vitexin-2-O-rhamnoside in hawthorn leaves flavonoids in rat using in situ and in vitro absorption models

The purpose of this study was to investigate the absorption mechanism of vitexin-2-O-rhamnoside, the index component in hawthorn leaves flavonoids (HLF) in the rat intestine, using two different absorption models, the in situ single-pass intestinal perfusion and the in vitro everted gut sac model. The effective permeability coefficients (P-eff) in the in situ single-pass intestinal perfusion experiments and the apparent permeability coefficients (P-app) in the in vitro everted gut sac experiments were calculated. Furthermore, the influences of the P-glycoprotein inhibitors, verapamil and digoxin, on the intestinal absorption of vitexin-2-O-rhamnoside in HLF were studied using the above-mentioned two models. Results showed that there were no significant differences in the absorption of vitexin-2-O-rhamnoside in HLF in four segments of the rat intestine, duodenum, jejunum, ileum, and colon, and at different concentrations of HLF ranging from 0.05 mg/ml to 0.5 mg/ml (P > 0.05). The P-eff values for vitexin-2-O-rhamnoside in the rat jejunal perfusion at the concentration of 0.05, 0.1, 0.25, and 0.5 mg/ml were (2.48 +/- 0.33) x 10(-5); (2.23 +/- 0.67) x 10(-5); (2.18 +/- 0.48) x 10(-5); and (2.25 +/- 0.17) x 10(-5) cm/s, respectively. But there was significant difference between absence and presence of verapamil or digoxin (P < 0.05). P-eff and P-app values of vitexin-2 ''-O-rhamnoside in HLF were increased in the presence of verapamil or digoxin. In conclusion, vitexin-2-O-rhamnoside can be classified into high permeability class drug according to the biopharmaceutical classification system. Passive diffusion dominates the absorptive transport behavior of vitexin-2-O-rhamnoside in HLF. The absorption and secretion are mediated by the efflux transport system, P-gp. The absorption of vitexin-2-O-rhamnoside in HLF can be enhanced administered together with P-gp inhibitors.