TITLE: Levistilide A inhibits liver fibrosis and angiogenesis |
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AUTHORS (FIRST NAME, LAST NAME): Zhimin Zhao1, Ye Tan1, Tao Guo1, Chenghai Liu1, 2 |
Institutional Author(s): |
INSTITUTIONS (ALL): 1. Institute of Liver Disease, ShuGuang Hospital, Shanghai University of Traditional Chinese Medicine, of Shanghai Academy of Traditional Chinese Medicine, 201203, China;, Shanghai, China.
2. E-Institute of Traditional Chinese Medicine Internal Medicine, Shanghai, 201203, China;, Shanghai, China.
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ABSTRACT BODY: Background and Aimevistilide A (the molecular weight is 380.48 and the formula is C24H28O4) is derived from Angelica Sinensis which has action of protecting liver injury in our previous works. In this study, we investigated its effects on liver fibrosis and angiogenesis in vivo and in vitro. Methods: Liver fibrosis was induced by hypodermic injection of CCl4 for 6 weeks in rats, and treated with 3 mg/kg and 6 mg/kg of Levistilide A from the 4th week of CCl4 intoxication to the end of experiment. Liver inflammation and fibrosis were observed by H&E and Sirius red staining, liver microvasculature was examined by synchrotron radiation X-ray two-dimensional imaging. Sinusoidal fenestration was detected by scanning electron microscope. SK-HEP-1 cells, a hepatic endothelial cell line, was hypoxia-induced by CoCl2. Cell viability was analyzed by MTT assay. vWF expression was examined by immunofluorescent staining. The levels of NO and NOS were observed by fluorescence probe. Tube formation assay and transgenic Zebrafish model were also performed. Results: Levistilide A attenuated liver inflammation and fibrosis in CCl4 rats. It could reduce hepatic microvessel texture and improve sinusoidal capillarization in vivo. It also could inhibit tube formation and the formation of functional vessels in transgenic zebrafish. It could protect SK-HEP-1 cells from the hypoxia injury, and decrease vWF protein expression but promote NO production in vitro. Conclusion: Levistilide A had potent effects against liver fibrosis and angiogenesis in vivo and in vitro. Keywords: Levistilide A; fibrosis; angiogenesis
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Effects of Levistilide A on Liver fibrosis and angiogenesis. (A) Sirius red staining. (B) Synchrotron radiation 2-d imaging. (C) Scanning electron microscope. (D) Transgenic Zebrafish. (E) The structure of Levistilide A.
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Co-Author Disclosure Status |
The following authors have completed their AASLD 2013 disclosure: Zhimin Zhao: Disclosure completed | Ye Tan: Disclosure completed | Tao Guo: Disclosure completed | Chenghai Liu: Disclosure completed |