18β-Glycyrrhetinic acid protects against alphanaphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway
文献类型：期刊论文
| 作者 | Wu Shouyan2; Cui Shichao1; Wang Le2; Zhang Yiting2; Yan Xiaoxia2; Lu Henglei2; Xing Guozhen2; Ren Jin2 ; Gong Likun2
|
| 刊名 | Acta Pharmacologica Sinica
 |
| 出版日期 | 2018 |
| 卷号 | 39期号:12页码:1865 |
| 关键词 | hepatoprotective effect cholestatic liver injury 18β-glycyrrhetinic acid (18b-GA) FXR Sirt1 bile acid transporters |
| ISSN号 | 1671-4083 |
| 英文摘要 | Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. Recently, 18β-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was reported to protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. However, its protective mechanism remains unclear. We hypothesized that 18b-GA may stimulate the signaling pathway of bile acid (BA) transportation in hepatocytes, resulting its hepatoprotective effect. According to the results, 18b-GA markedly attenuated ANIT-induced liver injury as indicated the hepatic plasma chemistry index and histopathology examination. In addition, the expression levels of nuclear factors, including Sirt1, FXR and Nrf2, and their target efflux transporters in the liver, which mainly mediate bile acid homeostasis in hepatocytes, significantly increased. Furthermore, we first revealed that 18b-GA treatment significantly activated FXR, and which can be significantly reduced by EX-527 (a potent and selective Sirt1 inhibitor), indicating that 18b-GA activates FXR through Sirt1. Taken together, 18b-GA confers hepatoprotection against ANITinduced cholestasis by activating FXR through Sirt1, which promotes gene expression of the efflux transporter, and consequently attenuates dysregulation of bile acid homeostasis in hepatocyte compartments. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/292715]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国科学院大学 2.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Wu Shouyan,Cui Shichao,Wang Le,et al. 18β-Glycyrrhetinic acid protects against alphanaphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway[J]. Acta Pharmacologica Sinica,2018,39(12):1865. |
| APA | Wu Shouyan.,Cui Shichao.,Wang Le.,Zhang Yiting.,Yan Xiaoxia.,...&Gong Likun.(2018).18β-Glycyrrhetinic acid protects against alphanaphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway.Acta Pharmacologica Sinica,39(12),1865. |
| MLA | Wu Shouyan,et al."18β-Glycyrrhetinic acid protects against alphanaphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway".Acta Pharmacologica Sinica 39.12(2018):1865. |
入库方式： OAI收割
来源：上海药物研究所
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