Influence and Mechanism of Bioactive Ingredients of Ligusticum chuan-xiong Hort. on the Transport of Gastrodin in MDCK-MDR1 Monolayer Cells / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the influence and mechanism of bioactive ingredients of Ligusticum chuanxiong Hort. on the transport of gastrodin based on cell culture model in vitro. METHODS: Cell toxicity of gastrodin, ligustilide, senkyunolide I and senkyunolide A were detected by MTT assay. The transport mechanism of gastrodin and the influence of ligustilide, senkyunolide I and senkyunolide A on the transport of gastrodin were studied in MDCK-MDR1 monolayer cells. The changed expressions of P-gp caused by ligustilide, senkyunolide I and senkyunolide A were analyzed by Western blotting. RESULTS: Gastrodin showed relatively poor absorption in MDCK-MDR1 cells for its apparent permeability coefficients were less than 1×10-6 cm·s-1. P-gp inhibitor made the Papp(B→A)/Papp(A→B) of gastrodin reduced from 1.29 to 0.79, which indicated that the transport of gastrodin was influenced by P-gp. In the presence of ligustilide(30 μg·mL-1) or senkyunolide I(120 μg·mL-1), the Papp(A→B) of gastrodin in MDCK-MDR1 were significantly increased(P<0.01). In the presence of senkyunolide A(120 μg·mL-1), the Papp(A→B) of gastrodin in MDCK-MDR1 were markedly increased(P<0.05). High, medium and low dose of ligustilide, senkyunolide A and senkyunolide I could significantly inhibit the expression of P-gp protein. CONCLUSION: The results indicate that the transport mechanism of gastrodin might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. Ligustilide, senkyunolide A and senkyunolide I increase the transport of gastrodin attribute to down-regulate P-gp expression.