Abstract��
OBJECTIVE To study the effect of tetramethylpyrazine and ginsenoside Rgl on the function and expression of p- glycoprotein in Caco-2 cells.METHODS HPLC-UV was used to detect the concentration of rhodamine-123,which was a substrate of p-glycoprotein.Flow cytometry was used to analyze the expression of p-glycoprotein in Caco-2 cell monolayers.RESULTS The cellular concentrations of rhodamine-123 were 1.7-fold and 8.2-fold as that of controls when being treated with tetramethylpyrazine at middle and high dose(120 and 240 mg��L-1).The p-glycoprotein protein levels were down-regulated by 53.6% and 38.8% compare with the controls,when being incubated with tetramethylpyrazine for 72 h.The total quantity of rhodamine-123 in receiver chambers of transwell at 1.5 h were increased by 30% and 80%,compared with the controls.Ginsenoside Rgl in high dose(20 mg��L-1) increased the cellular concentrations of rhodamine-123 to 3.5-fold as that of control,and was observed to increase the transport of rhodamine-by 30% and longer term(72 h) co-incubation of the Caco-2 cells with ginsenoside Rgl had no effect on the cellular p-glycoprotein protein levels.The cellular concentration of rhodamine-123 was 20.6-fold as that of the control when combining tetramethylpyrazine (120 mg��L-1)with ginsenoside Rgl(10 mg��L-1)in middle concentration.Longer term (72 h)co-incubation of the Caco-2 cells down-regulated the cellular p-glycoprotein protein levels by 61.8%,increased the total quantity of rhodamine-123 in receiver chambers at 1.5 h by 60%,compared with the control.CONCLUSION Tetramethylpyrazine is a substrate and inhibitor of p-glycoprotein,and it could significantly inhibit the function of p-glycoprotein,and seemed to act directly on the activity of p- glycoprotein or be a binding site competitor of rhodamine-123.Tetramethytpyrazine could significantly decrease the expression of p- glycoprotein after being incubated with Caco-2 cells in 72 h.Ginsenoside Rgl may be an inhibitor of p-glycoprotein.It could significantly inhibit the activity of p-glycoprotein at high concentration.Longer term (72 h) co-incubation of the Caco-2 cell monolayer with ginsenoside Rgl had no effect on p-glycoprotein levels.Ginsenoside Rgl inhibited the activity of p-glycoprotein without decreasing the expression of Caco-2 cell monolayer.Combining tetramethylpyrazine with ginsenoside Rgl showed a great synergistic effect on p- glyeoprotein mediated efflux and transport of rhodamine-123 in the cells but no synergistic effect on p-glyeoprotein's expression.
.Effects of Tetramethylpyrazine and Ginsenoside Rgl on p-Glycoprotein Function and Expression in Caco-2 Cells [J] Chinese Pharmaceutical Journal, 2008,V43(13): 987-991
2008, Vol. 43 
