New insights into salvianolic acid A action: Regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways ameliorates HFD-induced NAFLD in rats

Sci Rep. 2016 Jun 27:6:28734. doi: 10.1038/srep28734.

Abstract

Salvianolic acid A (SalA), one of the most efficacious polyphenol compounds extracted from Radix Salvia miltiorrhiza (Danshen), has been shown to possess many potential pharmacological activities. This study aimed to investigate whether SalA has hepatoprotective effects against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and to further explore the mechanism underlying this process. SalA treatment significantly attenuated HFD-induced obesity and liver injury, and markedly decreased lipid accumulation in HFD-fed rat livers. Moreover, SalA treatment ameliorated HFD-induced hepatic inflammation and oxidative stress by decreasing hepatotoxic levels of cytokines, suppressing the overproduction of reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) and preventing the decreased expression of superoxide dismutase (SOD). Importantly, SalA reversed the HFD- or palmitic acid (PA)-induced activation of the NLRP3 inflammasome, the nuclear translocation of ChREBP and the up-regulation of FAS, and these effects were accompanied by TXNIP down-regulation. However, TXNIP siRNA treatment partially abrogated the above-mentioned effects of SalA in PA-treated HepG2 cells. Together, our results demonstrated, for the first time, that SalA protects against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation, and these protective effects may partially due to regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / pharmacology*
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Dietary Fats / adverse effects*
  • Dietary Fats / pharmacology
  • Hep G2 Cells
  • Humans
  • Lipid Metabolism / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Non-alcoholic Fatty Liver Disease* / chemically induced
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Non-alcoholic Fatty Liver Disease* / prevention & control
  • Polyphenols / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Alkenes
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Carrier Proteins
  • Cell Cycle Proteins
  • Dietary Fats
  • Mlxipl protein, rat
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Polyphenols
  • TXNIP protein, rat
  • salvianolic acid