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Open AccessArticle

Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats

1
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China
2
Department of Pharmacy, Eye Ear Nose Throat Hospital of Fudan University, Shanghai 200031, China
3
Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
*
Author to whom correspondence should be addressed.
Molecules 2017, 22(11), 1809; https://doi.org/10.3390/molecules22111809
Received: 20 September 2017 / Accepted: 23 October 2017 / Published: 25 October 2017
(This article belongs to the Collection Herbal Medicine Research)
Our previous study showed that kurarinone was the main hepatotoxic ingredient of Sophora flavescens, accumulating in the liver. This study characterized the mechanism of Sophora flavescens extract (ESF) hepatotoxicity and hepatic accumulation of kurarinone. ESF impaired hepatic function and caused fat accumulation in the liver after oral administration (1.25 and 2.5 g/kg for 14 days in rats). Serum metabolomics evaluation based on high-resolution mass spectrometry was conducted and real-time PCR was used to determine the expression levels of CPT-1, CPT-2, PPAR-α, and LCAD genes. Effects of kurarinone on triglyceride levels were evaluated in HL-7702 cells. Tissue distribution of kurarinone and kurarinone glucuronides was analyzed in rats receiving ESF (2.5 g/kg). Active uptake of kurarinone and kurarinone glucuronides was studied in OAT2-, OATP1B1-, OATP2B1-, and OATP1B3-transfected HEK293 cells. Our results revealed that after oral administration of ESF in rats, kurarinone glucuronides were actively transported into hepatocytes by OATP1B3 and hydrolyzed into kurarinone, which inhibited fatty acid β-oxidation through the reduction of l-carnitine and the inhibition of PPAR-α pathway, ultimately leading to lipid accumulation and liver injury. These findings contribute to understanding hepatotoxicity of kurarinone after oral administration of ESF. View Full-Text
Keywords: Sophora flavescens; kurarinone; hepatotoxicity; metabolomics; steatosis; transporter Sophora flavescens; kurarinone; hepatotoxicity; metabolomics; steatosis; transporter
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MDPI and ACS Style

Jiang, P.; Zhang, X.; Huang, Y.; Cheng, N.; Ma, Y. Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats. Molecules 2017, 22, 1809. https://doi.org/10.3390/molecules22111809

AMA Style

Jiang P, Zhang X, Huang Y, Cheng N, Ma Y. Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats. Molecules. 2017; 22(11):1809. https://doi.org/10.3390/molecules22111809

Chicago/Turabian Style

Jiang, Peng; Zhang, Xiuwen; Huang, Yutong; Cheng, Nengneng; Ma, Yueming. 2017. "Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats" Molecules 22, no. 11: 1809. https://doi.org/10.3390/molecules22111809

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