Hepatoprotective Effects of Schisandra sphenanthera Extract against Lithocholic Acid–Induced Cholestasis in Male Mice Are Associated with Activation of the Pregnane X Receptor Pathway and Promotion of Liver Regeneration

• DOI: 10.1124/dmd.115.066969
• Publication Date: 2015-12-11T03:23:41Z
• Authors: Hang Zeng; Dongshun Li; Xiaoling Qin; Pan Chen; Huasen Tan; Xuezhen Zeng; Xi Li; Xiaomei Fan; Yiming Jiang; Yawen Zhou; Yixin Chen; Ying Wang; Min Huang; Huichang Bi
• Keywords: Pregnane X receptor; Schisandra; Constitutive androstane receptor; Lithocholic acid; Small heterodimer partner; Liver Regeneration; Farnesoid X receptor; Acetaminophen

We previously reported that the ethanol extract of <i>Schisandra sphenanthera</i> [Wuzhi (WZ) tablet] significantly protects against acetaminophen-induced hepatoxicity. However, whether WZ exerts a protective effect cholestasis remains unclear. In this study, on lithocholic acid (LCA)–induced intrahepatic in mice was characterized and involved mechanisms were investigated. pretreatment (350 mg/kg) with LCA reversed liver necrosis decreased serum alanine aminotransferase, aspartate alkaline phosphatase activity. More importantly, total bile acids bilirubin also remarkably reduced. Quantitative reverse-transcription polymerase chain reaction Western blot analysis showed hepatic expression pregnane X receptor (PXR) target genes such as CYP3A11 UDP-glucuronosyltransferase (UGT) 1A1 increased by treatment. Luciferase assays performed LS174T cells illustrated its six bioactive lignans could all activate human PXR. addition, treatment promoted regeneration via inhibition p53/p21 to induce cell proliferation–associated proteins cyclin D1 proliferating nuclear antigen. conclusion, has LCA-induced cholestasis, partially owing activation PXR pathway promotion regeneration.