NR1H4 and cholestasis: C. Shih, a herbal medicine withcostunolide as a major constituent, structurally interacts with FXRto prevent cholestasis.53 The binding ofthe compound to FXR significantly activated the FXR/SHP pathway; inhibitedCYP7A1 and CYP27A1 to control the bile acid synthetic process; andupregulated BSEP, MRP2, and NTCP to promote bile acid transport, consequentlyameliorating bile accumulation in the liver.