Mulberroside A suppresses PXR‐mediated transactivation and gene expression of P‐gp in LS174T cells

Mulberroside A (Mul A) is the main bioactive constituents of Sangbaipi, which is officially listed in the Chinese Pharmacopoeia. The pregnane X receptor (PXR) has been recognized as the critical mediator of human P‐glycoprotein (P‐gp) gene transactivation. In this study, the effect of Mul A on PXR‐mediated transactivation and gene expression of P‐gp was investigated. It was found that Mul A significantly suppressed PXR‐mediated P‐gp luciferase activity induced by rifampicin (Rif). Furthermore, Rif induced an elevation of P‐gp expression and transport activity, which was apparently suppressed by Mul A. However, Mul A did not suppress the P‐gp luciferase activity, P‐gp expression, and function in the absence of Rif. These findings suggest that Mul A suppresses PXR‐mediated transactivation and P‐gp expression induced by Rif. This should be taken into consideration to predict any potential herb–drug interactions when Mul A or Sangbaipi are co‐administered with Rif or other PXR agonist drugs.