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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Categories: 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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Figure 1

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CAR coordinately regulates the bilirubin clearance pathway. (a) Mice wer...
CAR coordinately regulates the bilirubin clearance pathway. (a) Mice were pretreated with different compounds (CO: corn oil control, TC: TCPOBOP, PCN, TCDD, and WY: WY-14,643) as indicated for 3 days. A single dose of bilirubin (10 mg/kg) was intravenously injected via the tail vein; total bilirubin was determined 60 minutes after the injection. *P < 0.01 relative to the control mice. (b) Total liver bilirubin from the same mice was determined. The average value of total bilirubin from each treatment is presented as a percentage relative to the value from the control treatment. *P < 0.01 relative to the control mice. (c) Total liver RNA was prepared from the same mice used in (a) and (b), and equivalent amounts of RNA from three individuals were pooled. Fifteen micrograms of each RNA sample were used for Northern hybridization with different probes as indicated.