4.5 Article

Salvianolic acid B protects against chronic alcoholic liver injury via SIRT1-mediated inhibition of CRP and ChREBP in rats

期刊

TOXICOLOGY LETTERS
卷 267, 期 -, 页码 1-10

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2016.12.010

关键词

Salvianolic acid B; SIRT1; Alcoholic liver injury; ChREBP; CRP

资金

  1. Chinese National Natural Science Foundation [81473266, 81372037, 81501699]

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Salvianolic acid B (SalB), a water-soluble polyphenol extracted from Radix Salvia miltiorrhiza, has been reported to possess many pharmacological activities. This study investigated the hepatoprotective effects of SaIB in chronic alcoholic liver disease (ALD) and explored the related signaling mechanisms. In vivo, SalB treatment significantly attenuated ethanol-induced liver injury by blocking the elevation of serum aminotransferase activities and markedly decreased hepatic lipid accumulation by reducing serum and liver triglyceride (TG) and total cholesterol (TC) levels. Moreover, SalB treatment ameliorated ethanol induced hepatic inflammation by decreasing the levels of hepatotoxic cytokines such as tumor necrosis factor-alpha. (TNF-alpha) and interleukin-6 (IL-6). Importantly, SalB pretreatment significantly increased the expression of SIRT1 and downregulated the expression of inflammatory mediator C-reactive protein (CRP) and lipoprotein carbohydrate response element-binding protein (ChREBP). In vitro, SaIB significantly reversed ethanol-induced down-regulation of SIRT1 and increased CRP and ChREBP expression. Interestingly, the effects of SaIB on SIRT1, CRP and ChREBP were mostly abolished by treatment with either SIRT1 siRNA or EX527, a specific inhibitor of SIRT1, indicating that SaIB decreased CRP and ChREBP expression by activating SIRT1. SaIB exerted anti-steatotic and anti-inflammatory effects against alcoholic liver injury by inducing SIRT1-mediated inhibition of CRP and ChREBP expression. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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