Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling

MadanKumar, Perumal; NaveenKumar, Perumal; Manikandan, Samidurai; Devaraj, Halagowder; NiranjaliDevaraj, Sivasithamparam

doi:10.1016/J.TAAP.2014.03.008

Title: Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling

Full Record
Other Related Research

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. - Highlights: • In vivomore »« less

Authors:

MadanKumar, Perumal; NaveenKumar, Perumal; Manikandan, Samidurai ^[1]; Devaraj, Halagowder ^[2]; NiranjaliDevaraj, Sivasithamparam ^[1]

Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu (India)
Department of Zoology, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu (India)

Publication Date:: Sun Jun 01 00:00:00 EDT 2014

OSTI Identifier:: 22439732

Resource Type:: Journal Article

Journal Name:: Toxicology and Applied Pharmacology

Additional Journal Information:: Journal Volume: 277; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; CELL CULTURES; CELL CYCLE; CELL PROLIFERATION; CONCENTRATION RATIO; ENZYMES; FIBROSIS; HUMAN POPULATIONS; IN VITRO; IN VIVO; LIPIDS; LIVER; MOLECULES; MORIN; PEROXIDES; RATS

Citation Formats


                    MadanKumar, Perumal, NaveenKumar, Perumal, Manikandan, Samidurai, Devaraj, Halagowder, and NiranjaliDevaraj, Sivasithamparam. Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling.  United States: N. p., 2014. 
        Web.  doi:10.1016/J.TAAP.2014.03.008.

Copy to clipboard


                    MadanKumar, Perumal, NaveenKumar, Perumal, Manikandan, Samidurai, Devaraj, Halagowder, & NiranjaliDevaraj, Sivasithamparam. Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling.  United States.  https://doi.org/10.1016/J.TAAP.2014.03.008

Copy to clipboard


                    MadanKumar, Perumal, NaveenKumar, Perumal, Manikandan, Samidurai, Devaraj, Halagowder, and NiranjaliDevaraj, Sivasithamparam. 2014.  
        "Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling".  United States.  https://doi.org/10.1016/J.TAAP.2014.03.008.

Copy to clipboard


                    
@article{osti_22439732,

  title        = {Morin ameliorates chemically induced liver fibrosis in vivo and inhibits stellate cell proliferation in vitro by suppressing Wnt/β-catenin signaling},

  author       = {MadanKumar, Perumal and NaveenKumar, Perumal and Manikandan, Samidurai and Devaraj, Halagowder and NiranjaliDevaraj, Sivasithamparam},

  abstractNote = {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. - Highlights: • In vivo and in vitro results revealed the active participation of Wnt signaling. • Morin at 50 μM inhibited LX-2 cell proliferation by suppressing Wnt signaling. • Morin exhibited hepatoprotective effects against DEN induced liver fibrosis. • Morin inhibited HSC activation in vivo by downregulating Wnt/β-catenin signaling.},

  doi          = {10.1016/J.TAAP.2014.03.008},

  url          = {https://www.osti.gov/biblio/22439732},
  journal      = {Toxicology and Applied Pharmacology},

  issn         = {0041-008X},

  number       = 2,

  volume       = 277,

  place        = {United States},

  year         = {Sun Jun 01 00:00:00 EDT 2014},

  month        = {Sun Jun 01 00:00:00 EDT 2014}

}

Copy to clipboard

Journal Article:

https://doi.org/10.1016/J.TAAP.2014.03.008

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Similar records in OSTI.GOV collections:

TRPM7 channel regulates PDGF-BB-induced proliferation of hepatic stellate cells via PI3K and ERK pathways

Journal Article Fang, Ling; Zhan, Shuxiang; Huang, Cheng; ... - Toxicology and Applied Pharmacology

TRPM7, a non-selective cation channel of the TRP channel superfamily, is implicated in diverse physiological and pathological processes including cell proliferation. Recently, TRPM7 has been reported in hepatic stellate cells (HSCs). Here, we investigated the contribution role of TRPM7 in activated HSC-T6 cell (a rat hepatic stellate cell line) proliferation. TRPM7 mRNA and protein were measured by RT-PCR and Western blot in rat model of liver fibrosis in vivo and PDGF-BB-activated HSC-T6 cells in vitro. Both mRNA and protein of TRPM7 were dramatically increased in CCl{sub 4}-treated rat livers. Stimulation of HSC-T6 cells with PDGF-BB resulted in a time-dependent increasemore »« less
https://doi.org/10.1016/J.TAAP.2013.08.009
Ligustrazine attenuates oxidative stress-induced activation of hepatic stellate cells by interrupting platelet-derived growth factor-β receptor-mediated ERK and p38 pathways

Journal Article Zhang, Feng; Ni, Chunyan; Kong, Desong; ... - Toxicology and Applied Pharmacology

Hepatic fibrosis represents a frequent event following chronic insult to trigger wound healing reactions with accumulation of extracellular matrix (ECM) in the liver. Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrogenesis. Compelling evidence indicates that oxidative stress is concomitant with liver fibrosis irrespective of the underlying etiology. Natural antioxidant ligustrazine exhibits potent antifibrotic activities, but the mechanisms are poorly understood. Our studies were to investigate the ligustrazine effects on HSC activation stimulated by hydrogen peroxide (H{sub 2}O{sub 2}), an in vitro model mimicking the oxidative stress in liver fibrogenesis, and to elucidate the possible mechanisms.more »« less
https://doi.org/10.1016/J.TAAP.2012.09.016
1,25-(OH){sub 2}-vitamin D{sub 3} prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4{sup −/−} model

Journal Article Hohenester, Simon; Nagel, Jutta; Wimmer, Ralf; ... - Biochemical and Biophysical Research Communications

Background/Purpose of the study: Vitamin D{sub 3}-deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D{sub 3}-administration has thus been proposed as a therapeutic approach. Vitamin D{sub 3} has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various mechanisms of action have been proposed, experimental evidence is limited. Here we test the hypothesis that active 1,25-(OH){sub 2}-vitamin D{sub 3} inhibits activation of hepatic stellate cells (HSC) in vitro and modulates liver-injury in vivo. Methods: Proliferation and activation of primary murine HSC were assessed by BrdU- and PicoGreen{sup ®}-assays, immunoblotting, immunofluorescence-microscopy, quantitative-PCR, andmore »« less
https://doi.org/10.1016/J.BBRC.2015.02.074
Targeted inhibition of disheveled PDZ domain via NSC668036 depresses fibrotic process

Journal Article Wang, Cong; Dai, Jinghong; Sun, Zhaorui; ... - Experimental Cell Research

In this study, we determined the effects of transforming growth factor-beta (TGF-β) and Wnt/β-catenin signaling on myofibroblast differentiation of NIH/3T3 fibroblasts in vitro and evaluated the therapeutic efficacy of NSC668036 in bleomycin-induced pulmonary fibrosis murine model. In vitro study, NSC668036, a small organic inhibitor of the PDZ domain in Dvl, suppressed β-catenin-driven gene transcription and abolished TGF-β1-induced migration, expression of collagen I and α-smooth muscle actin (α-SMA) in fibroblasts. In vivo study, we found that NSC668036 significantly suppressed accumulation of collagen I, α-SMA, and TGF-β1 but increased the expression of CK19, Occludin and E-cadherin that can inhibit pulmonary fibrogenesis. Becausemore »« less
https://doi.org/10.1016/J.YEXCR.2014.10.023
Ramalin, an antioxidant compound derived from Antarctic lichen, prevents progression of liver fibrosis induced by dimethylnitrosamine (DNM) in rats

Journal Article Kim, Min-Kyoung; Kim, Min; Yim, Joung; ... - Biochemical and Biophysical Research Communications

Highlights: • New chemical substance, “Ramalin”, derived from Antarctic lichen, acts as a powerful antioxidant and ROS scavenger. • Ramalin significantly reduces hepatic stellet cell activation, while also reducing malondialdehyde (MDA), and hydroxyproline (HP). • Ramalin offers hepatoprotection effect by ameliorating DMN-induced oxidative stress and hepatotoxicity. Hepatic fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM), primarily collagen, within the liver. Because reactive oxygen species (ROS) has been implicated in its pathogenesis, the use of antioxidants as a potential treatment has been broadly explored. Here, we investigated the hepatoprotective properties of ramalin (RM), a compound extracted from themore »« less
https://doi.org/10.1016/J.BBRC.2018.08.103

Similar Records