title: Aucubin and its hydrolytic derivative attenuate activation of hepatic stellate cells via modulation of TGF-β stimulation.
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.
authors.affiliation: 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.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Lv
authors.affiliation: 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.
authors.forename: Han
authors.initials: H
authors.lastname: Feng
authors.affiliation: 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.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The Affiliated Zhongshan Hospital, Xiamen University, Fujian 361004, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Qin
authors.affiliation: School of Pharmaceutical Sciences, Central South Univesity, Changsha 410013, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Ouyang
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D057888:Iridoid Glucosides / Q000494:pharmacology*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics; D011714:Pyrans / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D057888:Iridoid Glucosides; D011714:Pyrans; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; C006650:aucubin; C036921:aucubigenin; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human
keywords: Aucubigenin; Aucubin; Extracellular matrix; Human hepatic stellate cells; TGF-β1