Transport characteristics of hydroxysafflor yellow A across Caco-2 cell monolayer model / 中草药

ABSTRACT

Objective: To investigate the transport characteristics of hydroxysafflor yellow A (HSYA) in Danhong Injection across Caco-2 cell monolayer. Methods: Safe concentration range of HSYA against Caco-2 cell monolayer model was selected by MTT method; The effects of time, drug concentration, temperature, pH, P-gp inhibitor (Verapamil), and energy metabolism inhibitor (sodium azide) on the absorption of HSYA were observed by Caco-2 cell monolayer model; The multidrug resistance (MDR1) gene expression in Caco-2 cells was analyzed by the RT-PCR method. Results: The Papp of HSYA transport from apical (AP) side to basolateral (BL) side was in 2 × 10-6-5 × 10-6 cm/s, which showed a medium absorption. The transport of HSYA was positively correlated with time and concentration. The Papp of HSYA transport at 37°C has significant differences with those at 4 and 25°C (P < 0.01). The Papp of HSYA transport under pH 9.0 has significant differences with those under pH 5.0 and 7.4 (P < 0.01). The gene expression of MDR1 was significantly reduced by Verapamil, but the transport of HSYA was not influenced by Verapamil and sodium azide, the number of Papp(BL→AP)/Papp(AP→BL) was between 1 and 1.5, so the absorption of HSYA was basically in line with the passive diffusion. Conclusion: The transport of HSYA across Caco-2 cell monolayer model is passive diffusion, and is not influenced by the change of P-gp and energy metabolism. Low temperature and alkaline environment are not conducive to the absorption of HSYA.