Pregnane X receptor and natural products: beyond drug-drug interactions.
The pregnane X receptor (PXR, NR1I2) is a member of the nuclear receptor superfamily that is activated by a myriad of compounds and natural products in clinical use. Activation of PXR represents the basis for several clinically important drug-drug interactions. Although PXR activation has undesirable effects in patients on combination therapy, it also mediates the hepatoprotective effects exhibited by some herbal remedies. This review focuses on PXR activation by natural products and the potential therapeutic opportunities presented. In particular, the biological effects of St. John's Wort, gugulipid, kava kava, Coleus forskolii, Hypoxis, Sutherlandia, qing hao, wu wei zi, gan cao and other natural products are discussed. The impact of these natural products on drug metabolism and hepatoprotection is highlighted in the context of activation and antagonism of PXR.
Staudinger
Jeff L
JL
University of Kansas, Department of Pharmacology and Toxicology, 5044 Malott Hall, Lawrence, KS 66045, USA. stauding@ku.edu
Ding
Xunshan
X
Lichti
Kristin
K
D000818:Animals; D001688:Biological Products / Q000378:metabolism / Q000494:pharmacology*; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D000077297:Pregnane X Receptor; D011485:Protein Binding / Q000502:physiology; D011987:Receptors, Steroid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism / Q000494:pharmacology*
D001688:Biological Products; C000625852:NR1I2 protein, human; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D047488:Retinoid X Receptors; D015262:Xenobiotics