Xiaochao Ma

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, USA

Nuclear receptors are a class of transcription factors that are critical for the development, homeostasis, and metabolism of the organism.  Functions of nuclear receptors are predominantly ligand-dependent.  Many chemicals in herbal products have been identified as ligands of constitutive androstane receptor (CAR) and pregnane X receptor (PXR), the two important nuclear receptors that modulate metabolism of endobiotics and xenobiotics.  The efficacy of Yin Zhi Huang for treatment of neonatal jaundice is dependent on CAR, which upregulates the expression of bilirubin glucuronyl transferase and increases bilirubin clearance.  6,7-Dimethylesculetin, a CAR activator, is an active component of Yin Zhi Huang.  The PXR regulates the genes encoding drug metabolizing enzymes and transporters, such as cytochrome P450 3A4 and P-glycoprotein.  Activation of PXR is associated with both bioactivation and detoxification, which may lead to herb-drug interactions and adverse drug reactions.  Hyperforin, the main active ingredient of hypericum perforatum (St. John's Wort), is a potent PXR activator.  N-methylcytisine in sophora flavescens has also been identified as a PXR activator.  In summary, nuclear receptors are important targets of herbal products, which potentially affect the efficacy and safety of herbal products.