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

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

Author information

1
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China; Department of Pharmacy, The Affiliated Zhongshan Hospital, Xiamen University, Fujian 361004, China.
2
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China; Department of Pharmacy, Henan Province People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
3
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China.
4
Department of Pharmacy, The Affiliated Zhongshan Hospital, Xiamen University, Fujian 361004, China.
5
School of Pharmaceutical Sciences, Central South Univesity, Changsha 410013, China.
6
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
7
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China. Electronic address: ouyangyj@163.com.

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

PMID:
28199906
DOI:
10.1016/j.etap.2017.02.012
[Indexed for MEDLINE]

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