Helenalin attenuates alcohol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and suppressing HSC activation.
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 α 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-β1, TNF-α, IL-6 and IL-1β and myeloperoxidase, via down-regulation of NF-κB. Helenalin significantly decreased collagen deposition by reducing the profibrotic cytokines like transforming growth factor-β, platelet-derived growth factor-β 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 α-SMA and TGF-β 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.
Guangxi Medical University, Nanning 530021, China.
Xing
X
Lin
Guangxi Medical University, Nanning 530021, China.
Shijun
S
Zhang
Guangxi Medical University, Nanning 530021, China.
Renbin
R
Huang
Guangxi Medical University, Nanning 530021, China.
Ling
L
Wei
Guangxi Medical University, Nanning 530021, China.
Shimei
S
Tan
The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
Shuang
S
Liang
The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
Yuanchun
Y
Tian
The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
Xiaoyan
X
Wu
The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
Zhongpeng
Z
Lu
The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China. Electronic address: hqf00@126.com.
Quanfang
Q
Huang
D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane; D013047:Specific Pathogen-Free Organisms
D016207:Cytokines; D016328:NF-kappa B; D010936:Plant Extracts; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D000431:Ethanol; C001329:helenalin
Alcohol; Centipeda minima; Helenalin; Hepatic fibrosis