壮药是我国药材资源的重要组成部分, 其中的南五味子属植物黑老虎根在民间广泛应用。挖掘民族药物资源，探索抗非酒精性脂肪性肝病（NAFLD）的药物及作用机制具有重要的社会经济效益。我们前期研究工作表明：黑老虎根提取物对大鼠NAFLD具有明显改善作用，所含Gomisin E是NAFLD防治靶标—孕烷X受体（PXR）的强效拮抗剂，且对hPXR和mPXR无选择性。本项目拟进一步运用天然产物分离纯化、光谱结构鉴定技术从黑老虎根中活性追踪和分离制备新的联苯环辛烯类等成分，以稳定转染hPXR/rPXR和荧光素酶报告基因的DPX2/rPXR细胞系为工具发现强效低毒的新型PXR拮抗剂。采用FFA诱导的体外肝细胞脂肪变性和STZ+HFD诱导野生型与人源化PXR基因的C57BL/6J小鼠NAFLD模型，围绕甘油三酯代谢与炎症信号通路，探讨药物作用特点与机制, 为黑老虎的合理开发并应用于防治NAFLD提供科学依据。

Zhuang medicine is an important part of medicinal resources in China, and the Radix Kadsurae Coccineae which is originated from Kadsura genus has been wildly used in popular. Mining ethical medicine resources and exploring the effective drug and action mechanism towards nonalcoholic fatty liver disease (NAFLD) has important social and economic benefits. Our previous research indicated that Radix Kadsurae Coccineae extraction can significantly ameliorate rats with NAFLD, and the containing constituent lignan gomisin E is a potent antagonist of human and rodent pregnane X receptor (PXR) which is an effective target towards NAFLD. Furtherly this project intends to use natural product separation and purification as well as spectral technology to track and prepare more bioactive dibenzocyclooctadiene lignan and other constituents from Radix Kadsurae Coccinea. We will adopt the DPX2 cell line which is derived from HepG2 cells with the stable transfection of human PXR and a luciferase reporter gene linked with a human PXR response element identified in the CYP3A4 gene promoter and rPXR cell lines to find potent and low toxic PXR antagonist with prospects of development. With in vitro hepatic steatosis cells induced by FFA and in vivo NAFLD model using C57BL/6J wild type and humanized PXR engineering mice on a C57BL/6J background treated with STZ+HFD, triglyceride metabolism and inflammatory signaling pathways were checked and drug action characteristic and mechanism were analyzed. This project can also provide scientific evidence for the rational development and use of Kadsuracoccinea (Lem.)A. C. Smith to prevent and treat NAFLD.