title: A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR.
abstract: Yin Zhi Huang, a decoction of Yin Chin (Artemisia capillaris) and three other herbs, is widely used in Asia to prevent and treat neonatal jaundice. We recently identified the constitutive androstane receptor (CAR, NR1I3) as a key regulator of bilirubin clearance in the liver. Here we show that treatment of WT and humanized CAR transgenic mice with Yin Zhi Huang for 3 days accelerates the clearance of intravenously infused bilirubin. This effect is absent in CAR knockout animals. Expression of bilirubin glucuronyl transferase and other components of the bilirubin metabolism pathway is induced by Yin Zhi Huang treatment of WT mice or mice expressing only human CAR, but not CAR knockout animals. 6,7-Dimethylesculetin, a compound present in Yin Chin, activates CAR in primary hepatocytes from both WT and humanized CAR mice and accelerates bilirubin clearance in vivo. We conclude that CAR mediates the effects of Yin Zhi Huang on bilirubin clearance and that 6,7-dimethylesculetin is an active component of this herbal medicine. CAR is a potential target for the development of new drugs to treat neonatal, genetic, or acquired forms of jaundice.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Wendong
authors.initials: W
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: David D
authors.initials: DD
authors.lastname: Moore
mesh_terms: D000818:Animals; D019306:Artemisia; D001628:Beverages; D001663:Bilirubin / Q000378:metabolism*; D000090702:Constitutive Androstane Receptor; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000517:prevention & control; D008657:Metabolic Clearance Rate; D051379:Mice; D008822:Mice, Transgenic; D008517:Phytotherapy; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D000090702:Constitutive Androstane Receptor; D004365:Drugs, Chinese Herbal; C000716327:NR1I3 protein, human; C000716328:Nr1i3 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D001663:Bilirubin