A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR
Wendong Huang, … , Jun Zhang, David D. Moore
Wendong Huang, … , Jun Zhang, David D. Moore
Published January 1, 2004
Citation Information: J Clin Invest. 2004;113(1):137-143. https://doi.org/10.1172/JCI18385.
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Article Hepatology

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

Wendong Huang, Jun Zhang, David D. Moore

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Yin Zhi Huang treatment stimulates bilirubin clearance in WT, but not CA...
Yin Zhi Huang treatment stimulates bilirubin clearance in WT, but not CAR, knockout mice. (a) Groups of four WT or CAR–/– mice were gavaged with either saline (PBS), control (CO), or Yin Zhi Huang (YZH) decoction (10 ml/kg/day) for 3 days. On the fourth day, mice were subjected to an acute bilirubin clearance assay, and total serum bilirubin was determined as described. *P < 0.05 relative to the control mice. (b) Total liver RNA was prepared from the animals as in (a). Equivalent amounts of RNA were pooled from four individuals, and 15 μg of each RNA sample was used for Northern hybridization with different probes as indicated. (c) Four groups of humanized CAR mice were treated with either PBS or increasing concentrations of YZH (2.5, 5 or 10 ml/kg/day) for 3 days. An acute bilirubin clearance assay, as well as Northern hybridization with CYP2B10 and human CAR probes, was carried out.