期刊
FITOTERAPIA
卷 95, 期 -, 页码 203-213出版社
ELSEVIER
DOI: 10.1016/j.fitote.2014.03.020
关键词
Helenalin; Centipeda minima; Alcohol; Hepatic fibrosis
资金
- National Natural Science Foundation of China [81260674, 81260505]
- Guangxi Natural Science Foundation [2013GXNSFAA019146, 2013GXNSFAA019150]
A compound was isolated from Centipeda minima using bioassay-guided screening. The structure of this compound was elucidated based on its spectral data, and it was identified as helenalin. The hepatoprotective effect of helenalin was evaluated using a liver fibrosis model induced by intragastric administration with alcohol within 24 weeks in rats. The results revealed that helenalin significantly prevented alcohol-induced hepatic injury and fibrogenesis, as evidenced by the decrease in serum aminotransferase, the attenuation of histopathological changes, and the inhibition of the hepatic fibrosis indicators, such as hyaluronic acid, type III precollagen, laminin, hydroxyproline and collagen alpha type I. Mechanistically, studies showed that helenalin expedited ethanol metabolism by enhancing the alcohol and aldehyde dehydrogenase activities. Furthermore, helenalin alleviated lipid peroxidation, recruited the antioxidative defense system, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TGF-beta 1, TNF-alpha, IL-6 and IL-1 beta and myeloperoxidase, via down-regulation of NF-kappa B. Helenalin significantly decreased collagen deposition by reducing the profibrotic cytokines like transforming growth factor-beta, platelet-derived growth factor-beta and connective tissue growth factor, and promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9. In addition, helenalin inhibited HSC activation as evidenced by the down-regulation of alpha-SMA and TGF-beta levels. In conclusion, helenalin had a significant protective effect on chronic ethanol-induced hepatic fibrosis and may be a major bioactive ingredient of C. minima. (C) 2014 Elsevier B.V. All rights reserved.
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