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

- The effects and mechanisms of aucubin and aucubigenin on liver fibrosis were investigated.
- Aucubin and aucubigenin both suppressed TGF-β1-stimulated activation of LX-2 cells and ECM deposition.
- Aucubin and aucubigenin also attenuated the generation of ROS stimulated by TGF-β1 through suppressing the activity of Nox4.
- Aucubin and aucubigenin would be promising therapeutic candidates for liver fibrosis.

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.

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