18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway
| العنوان: | 18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway |
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| المؤلفون: | Cui Shichao, Yi-ting Zhang, Likun Gong, Le Wang, Henglei Lu, Guozhen Xing, Xiao-xia Yan, Jin Ren, Shou-yan Wu |
| المصدر: | Acta Pharmacologica Sinica. 39:1865-1873 |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, NF-E2-Related Factor 2, medicine.drug_class, Receptors, Cytoplasmic and Nuclear, Pharmacology, Protective Agents, Article, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Sirtuin 1, Cholestasis, medicine, Animals, Pharmacology (medical), Enterohepatic circulation, Liver injury, Bile acid, Chemistry, General Medicine, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, 1-Naphthylisothiocyanate, Hepatoprotection, 030220 oncology & carcinogenesis, Hepatocyte, Glycyrrhetinic Acid, Signal transduction, Homeostasis, Signal Transduction |
| الوصف: | 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 ANIT-induced 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. |
| تدمد: | 1745-7254 1671-4083 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::595139fd88bc023c5c7657e0cfedcf9cTest https://doi.org/10.1038/s41401-018-0110-yTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....595139fd88bc023c5c7657e0cfedcf9c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17457254 16714083 |
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