PT  - JOURNAL ARTICLE
AU  - Hang Zeng
AU  - Dongshun Li
AU  - Xiaoling Qin
AU  - Pan Chen
AU  - Huasen Tan
AU  - Xuezhen Zeng
AU  - Xi Li
AU  - Xiaomei Fan
AU  - Yiming Jiang
AU  - Yawen Zhou
AU  - Yixin Chen
AU  - Ying Wang
AU  - Min Huang
AU  - Huichang Bi
TI  - Hepatoprotective Effects of <em>Schisandra sphenanthera</em> Extract against Lithocholic Acid–Induced Cholestasis in Male Mice Are Associated with Activation of the Pregnane X Receptor Pathway and Promotion of Liver Regeneration
AID  - 10.1124/dmd.115.066969
DP  - 2016 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 337--342
VI  - 44
IP  - 3
4099  - http://dmd.aspetjournals.org/content/44/3/337.short
4100  - http://dmd.aspetjournals.org/content/44/3/337.full
SO  - Drug Metab Dispos2016 Mar 01; 44
AB  - We previously reported that the ethanol extract of Schisandra sphenanthera [Wuzhi (WZ) tablet] significantly protects against acetaminophen-induced hepatoxicity. However, whether WZ exerts a protective effect against cholestasis remains unclear. In this study, the protective effect of WZ on lithocholic acid (LCA)–induced intrahepatic cholestasis in mice was characterized and the involved mechanisms were investigated. WZ pretreatment (350 mg/kg) with LCA significantly reversed liver necrosis and decreased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activity. More importantly, serum total bile acids and total bilirubin were also remarkably reduced. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis showed that hepatic expression of pregnane X receptor (PXR) target genes such as CYP3A11 and UDP-glucuronosyltransferase (UGT) 1A1 were significantly increased by WZ treatment. Luciferase assays performed in LS174T cells illustrated that WZ extract and its six bioactive lignans could all activate human PXR. In addition, WZ treatment significantly promoted liver regeneration via inhibition of p53/p21 to induce cell proliferation–associated proteins such as cyclin D1 and proliferating cell nuclear antigen. In conclusion, WZ has a protective effect against LCA-induced intrahepatic cholestasis, partially owing to activation of the PXR pathway and promotion of liver regeneration.