title: Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling.
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.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: MadanKumar
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: NaveenKumar
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
authors.forename: Samidurai
authors.initials: S
authors.lastname: Manikandan
authors.affiliation: Department of Zoology, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
authors.forename: Halagowder
authors.initials: H
authors.lastname: Devaraj
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India. Electronic address: niranjali@yahoo.com.
authors.forename: Sivasithamparam
authors.initials: S
authors.lastname: NiranjaliDevaraj
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D019610:Cytoprotection; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism*; D047309:Flavones
chemical_list: D019938:Cyclin D1; D004052:Diethylnitrosamine; D005419:Flavonoids; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D051176:beta Catenin; C495270:CTNNB1 protein, human; C530106:Ccnd1 protein, rat; C495268:Ctnnb1 protein, rat; C008548:morin; D047309:Flavones; C000605506:GSK3B protein, human; C000605508:Gsk3b protein, rat
keywords: Diethylnitrosamine; G1 cell cycle arrest; LX-2 cells; Liver fibrosis; Morin; β-Catenin