Baicalin attenuates non-alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, inflammation and fibrosis in mice

Life Sci. 2018 Jan 1:192:46-54. doi: 10.1016/j.lfs.2017.11.027. Epub 2017 Nov 20.

Abstract

Aims: Baicalin (BA), an active flavonoid compound originating from the herb of Scutellaria baicalensis Georgi, has been previously shown to exert anti-inflammation and anti-oxidant effects in liver diseases. However, the potential role of BA in the regulation of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we newly explored the hepatoprotective effects of BA in MCD diet-induced NASH by ameliorating hepatic steatosis, inflammation, fibrosis and apoptosis.

Main methods: NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4weeks. The mice were simultaneously treated with or without BA for 4weeks. Serum liver functional markers and inflammatory indicators were assessed by biochemical and ELISA methods, respectively. The livers were histologically examined using H&E, Oil Red O and Masson's trichrome staining methods. The qRT-PCR, IHC and Western blotting assays were applied to analyze mechanisms underlying BA protection.

Key findings: BA treatment significantly attenuated MCD diet-induced hepatic lipid accumulation partly through regulating the expression of SREBP-1c, FASN, PPARα and CPT1a. BA treatment dramatically suppressed MCD diet-induced hepatic inflammation, which was associated with decrease in serum TNF-α, IL-1β and MCP-1 production, macrophage influx and suppression of nuclear factor-κB activation. Additionally, BA was proved to prevent liver fibrosis, which appears to be mediated by inhibition of α-SMA, TGF-β1 and Col1A1. Furthermore, BA markedly inhibited hepatocyte apoptosis and cleaved caspase-3 protein expression in MCD diet-induced mice.

Significance: These results provide a possible basis of the underlying mechanism for the application of BA in the treatment of NASH.

Keywords: Apoptosis; Baicalin; Fibrosis; Inflammation; Lipid metabolism; Non-alcoholic steatohepatitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Chemokine CCL2 / antagonists & inhibitors
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / genetics
  • Choline Deficiency / drug therapy
  • Choline Deficiency / pathology
  • Diet
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / genetics
  • Lipid Metabolism / drug effects*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / pathology
  • Liver Function Tests
  • Male
  • Methionine / deficiency
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Flavonoids
  • Interleukin-1beta
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • baicalin
  • Methionine
  • Casp3 protein, mouse
  • Caspase 3