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Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2014 Jun 01; Vol. 277 (2), pp. 210-20. Date of Electronic Publication: 2014 Mar 20. - Publication Year :
- 2014
-
Abstract
- The anti-fibrotic effect of morin was examined in LX-2 cells (culture-activated human hepatic stellate cells) and in diethylnitrosamine induced rat model of liver fibrosis. The in vitro study was designed to determine whether morin affects the survival of cultured LX-2 cells, while the in vivo study was designed to evaluate the antioxidant and anti-fibrotic efficacy of morin on diethylnitrosamine induced liver fibrosis in male albino Wistar rat. The activities of liver function enzymes in serum, liver lipid peroxide levels, activities of serum antioxidant enzymes and liver architecture were monitored to cast light on the antioxidant and hepatoprotective nature of morin. To establish the anti-fibrotic effects of morin, the levels of key Wnt signaling molecules which are strongly associated with the signal transduction pathway of HSC activation were measured. Overall, from the in vitro results, it was observed that morin at 50 μM concentration inhibited the proliferation of cultured LX-2 cells, inhibited Wnt signaling and induced G1 cell cycle arrest. The in vivo results further confirmed that morin by downregulating the expressions of GSK-3β, β-catenin and cyclin D1 ameliorated DEN-induced liver fibrosis. Hence morin could be employed as a promising chemopreventive natural supplement for liver fibrosis.<br /> (Copyright © 2014. Published by Elsevier Inc.)
- Subjects :
- Animals
Cell Line
Cell Survival drug effects
Cyclin D1 metabolism
Cytoprotection
Diethylnitrosamine
Dose-Response Relationship, Drug
G1 Phase Cell Cycle Checkpoints drug effects
Glycogen Synthase Kinase 3 metabolism
Glycogen Synthase Kinase 3 beta
Hepatic Stellate Cells metabolism
Hepatic Stellate Cells pathology
Humans
Lipid Peroxidation drug effects
Liver metabolism
Liver pathology
Liver Cirrhosis, Experimental chemically induced
Liver Cirrhosis, Experimental metabolism
Liver Cirrhosis, Experimental pathology
Male
Oxidative Stress drug effects
Rats
Rats, Wistar
Time Factors
Cell Proliferation drug effects
Flavonoids pharmacology
Hepatic Stellate Cells drug effects
Liver drug effects
Liver Cirrhosis, Experimental prevention & control
Wnt Signaling Pathway drug effects
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 277
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 24657339
- Full Text :
- https://doi.org/10.1016/j.taap.2014.03.008