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Ethyl acetate fraction of Amomum xanthioides improves bile duct ligation-induced liver fibrosis of rat model via modulation of pro-fibrogenic cytokines.
- Source :
-
Scientific reports [Sci Rep] 2015 Sep 28; Vol. 5, pp. 14531. Date of Electronic Publication: 2015 Sep 28. - Publication Year :
- 2015
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Abstract
- We investigated anti-hepatofibrotic effects of ethyl acetate fraction of Ammomum xanthoides (EFAX) using bile duct ligation (BDL)-induced hepatic fibrosis in a rat model. Male SD rats (6 weeks old) underwent BDL followed by 15 days of orall administration of EFAX (12.5, 25 or 50 mg/kg) or ursodeoxycholic acid (25 mg/kg). BDL caused animal death, ascites formation, alterations in serum biochemistries, and severe hepatic injury with excessive collagen deposition, whereas EFAX treatment significantly attenuated these effects. BDL markedly increased the pro-fibrogenic cytokines (TGF-β, PDGF-β, and CTGF) and the extracellular matrix indicators α-SMA, TIMP-1 and collagen type 1 in hepatic proteins and gene expression levels, which were notably normalized by EFAX treatment. EFAX also markedly normalized pro-fibrogenic signaling molecules including Smad2/3, Smad7, Akt, p44/42, and p38. We further explored EFAX mechanisms of actions using LX-2 cells (human derived hepatic stellate cell line). Pre-treatment with EFAX drastically attenuated the activation of α-SMA and Smad2/3, which are downstream molecules of TGF-β. These findings suggest that EFAX may be a potent anti-hepatofibrotic agent, and its corresponding mechanisms primarily involve the modulation of pro-fibrogenic cytokines.
- Subjects :
- Acetates chemistry
Actins genetics
Actins metabolism
Animals
Bile Ducts surgery
Body Weight drug effects
Collagen metabolism
Cytokines genetics
Disease Models, Animal
Gene Expression Regulation drug effects
Hepatic Stellate Cells drug effects
Hepatic Stellate Cells metabolism
Ligation
Lipid Peroxidation drug effects
Liver Cirrhosis drug therapy
Liver Cirrhosis mortality
Liver Cirrhosis pathology
Liver Function Tests
Male
Organ Size drug effects
Plant Extracts chemistry
Rats
Signal Transduction drug effects
Acetates pharmacology
Amomum chemistry
Cytokines metabolism
Liver Cirrhosis etiology
Liver Cirrhosis metabolism
Plant Extracts pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26412144
- Full Text :
- https://doi.org/10.1038/srep14531