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

Toxicol Lett. 2017 Feb 5:267:1-10. doi: 10.1016/j.toxlet.2016.12.010. Epub 2016 Dec 15.

Abstract

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 SalB 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-α (TNF-α) 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, SalB significantly reversed ethanol-induced down-regulation of SIRT1 and increased CRP and ChREBP expression. Interestingly, the effects of SalB on SIRT1, CRP and ChREBP were mostly abolished by treatment with either SIRT1 siRNA or EX527, a specific inhibitor of SIRT1, indicating that SalB decreased CRP and ChREBP expression by activating SIRT1. SalB exerted anti-steatotic and anti-inflammatory effects against alcoholic liver injury by inducing SIRT1-mediated inhibition of CRP and ChREBP expression.

Keywords: Alcoholic liver injury; CRP; ChREBP; SIRT1; Salvianolic acid B.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Benzofurans / pharmacology*
  • Biomarkers / blood
  • Carbazoles / pharmacology
  • Carrier Proteins / metabolism*
  • Chronic Disease
  • Cytokines / metabolism
  • Cytoprotection
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hep G2 Cells
  • Hepatocyte Nuclear Factor 1-alpha / metabolism
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Inflammation Mediators / metabolism
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Liver Diseases, Alcoholic / enzymology
  • Liver Diseases, Alcoholic / genetics
  • Liver Diseases, Alcoholic / pathology
  • Liver Diseases, Alcoholic / prevention & control*
  • Male
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Transfection

Substances

  • 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
  • Anti-Inflammatory Agents
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Benzofurans
  • Biomarkers
  • Carbazoles
  • Carrier Proteins
  • Crp protein, rat
  • Cytokines
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Histone Deacetylase Inhibitors
  • Inflammation Mediators
  • Mlxipl protein, rat
  • RNA, Small Interfering
  • salvianolic acid B
  • SIRT1 protein, human
  • Sirt1 protein, rat
  • Sirtuin 1