Aucubin and its hydrolytic derivative attenuate activation of hepatic stellate cells via modulation of TGF-β stimulation

Environ Toxicol Pharmacol. 2017 Mar:50:234-239. doi: 10.1016/j.etap.2017.02.012. Epub 2017 Feb 8.

Abstract

Eucommia ulmoides is an important traditional Chinese medicine and has been used as a tonic with a long history. Aucubin is an active component extracted from Eucommia ulmoides, which has liver-protection effects. However the mechanisms are still unclear. To investigate the inhibitory effects and the underlying mechanisms of aucubin on TGF-β1-induced activation of hepatic stellate cells and ECM deposition, Human hepatic stellate cells (LX-2 cells) were incubated with TGF-β1 to evaluate the anti-fibrotic effect of aucubin. Western blot was used to investigate the expression of α-SMA, Col I, Col III, MMP-2 and TIMP-1. ROS production was monitored using DCFH-DA probe, and NOX4 expression was detected by Real-time PCR. Results indicated that TGF-β1 stimulated the activation and ECM deposition of LX-2 cells. Compared with the control group, aucubin and aucubigenin both reduced the protein expression of α-SMA, Col I, Col III and MMP-2 in LX-2 cells. Aucubin and aucubigenin also suppressed the generation of ROS and down-regulated the NOX4 mRNA expression. Taken together, aucubin and aucubigenin both inhibit the activation and ECM deposition of LX-2 cells activated by TGF-β1. Aucubin and aucubigenin are potential therapeutic candidate drugs for liver fibrosis.

Keywords: Aucubigenin; Aucubin; Extracellular matrix; Human hepatic stellate cells; TGF-β1.

MeSH terms

  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Extracellular Matrix / drug effects
  • Gene Expression Regulation / drug effects
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / drug effects*
  • Hepatic Stellate Cells / metabolism
  • Humans
  • Iridoid Glucosides / pharmacology*
  • NADPH Oxidase 4
  • NADPH Oxidases / genetics
  • Pyrans / pharmacology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • Iridoid Glucosides
  • Pyrans
  • Reactive Oxygen Species
  • Transforming Growth Factor beta1
  • aucubin
  • aucubigenin
  • NADPH Oxidase 4
  • NADPH Oxidases
  • NOX4 protein, human