Effects of Coscinium Fenestratum stem extract on function and expression of P-Glycoprotein

Abstract

This study aimed to investigate the effects of Coscinium fenestratum stem extract on P-glycoprotein (Pgp) function and MDR1 expression in porcine renal epithelial (LLC-PK1) and its MDR1 transfected (LLC-MDR1) and its vinblastine (VBL)-induced MDR1 transfected (LLC-VBL) cell lines. C. fenestratum stems were extracted by maceration with 80% ethanol. The result showed that the non-toxic concentration of C. fenestratum extract (100 µg/ml) potentiated the effect of VBL (Pgp-substrate)-induced cytotoxicity in LLC-VBL and LLC-MDR1 cells. This effect was stronger in LLC-VBL cells than in LLC-MDR1 cells which it was well correlated with significantly increase accumulation of intracellular fluorescent rhodamine 123, a Pgp-substrate. Interestingly, the C. fenestratum extract decreased Pgp-ATPase activity in both Pgp-overexpressed cells. The major compound in C. fenestratum extract, berberine, at the non-toxic concentration of 1 µg/ml significantly potentiated the effect of VBL-induced cytotoxicity in LLC-VBL cells, but it did not affect LLC-MDR1 cells. It had no effect on rhodamine 123 accumulation and Pgp-ATPase activity in both Pgp-overexpression cells. However, both C. fenestratum extract and berberine had no effect on Pgp expression determined by Western blot analysis. Taken together, our findings indicated that C. fenestratum ethanolic stem extract is a P-glycoprotein inhibitor by inhibiting ATPase activity without affecting Pgp-expression. Therefore, co-administration of Pgp-substrate medicines with C. fenestratum extract may lead to undesirable drug-herb interaction.