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      Hepatoprotective effects of Limonium tetragonum, edible medicinal halophyte growing near seashores

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          Abstract

          Background:

          During the process of hepatic fibrosis, the activation of hepatic stellate cells (HSCs) is responsible for the increased formation and reduced degradation of extracellular matrix in the liver. By employing the hepatic stellate cell line, HSC-T6, it was found that the methanol extract of Limonium tetragonum, a halophyte living in salt marsh near south and western seashores of Korea significantly inhibited the proliferation of HSC-T6 cells.

          Objective:

          In the present study, we attempted to investigate the antifibrotic effects of the mathanolic extract of L. tetragonum (MELT) in the activated HSC-T6 cells.

          Materials and Methods:

          The proliferation of HSC-T6 was stimulated by culturing environment or platelet-derived growth factor (PDGF-BB) insult, and then the inhibitory activities of MELT were measured.

          Results:

          It was found that MELT suppressed the proliferation of the activated HSC-T6 in concentration- and time-dependent manners. The increased collagen deposition in the activated HSC-T6 cells was also decreased by the treatment of MELT. The maximal dose of MELT, however, had little effect on primary cultured rat hepatocytes. Wlammatory cytokine, tumor necrosis factor alpha (TNF-α) produced by lipopolysaccharide-stimulated RAW264.7 macrophages was inhibited by MELT.

          Conclusion:

          Collectively, the above results demonstrated that MELT suppressed HSCs proliferation but not in hepatocytes, implying that L. tetragonum may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis.

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          Most cited references30

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          Liver fibrosis.

          Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-beta1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies.
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            Regulation of PDGF and its receptors in fibrotic diseases.

            Platelet-derived growth factor (PDGF) isoforms play a major role in stimulating the replication, survival, and migration of myofibroblasts during the pathogenesis of fibrotic diseases. During fibrogenesis, PDGF is secreted by a variety of cell types as a response to injury, and many pro-inflammatory cytokines mediate their mitogenic effects via the autocrine release of PDGF. PDGF action is determined by the relative expression of PDGF alpha-receptors (PDGFRalpha) and beta-receptors (PDGFRbeta) on the surface of myofibroblasts. These receptors are induced during fibrogenesis, thereby amplifying biological responses to PDGF isoforms. PDGF action is also modulated by extracellular binding proteins and matrix molecules. This review summarizes the literature on the role of PDGF and its receptors in the development of fibrosis in a variety of organ systems, including lung, liver, kidney, and skin.
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              Macrophages and tissue injury: agents of defense or destruction?

              The past several years have seen the accumulation of evidence demonstrating that tissue injury induced by diverse toxicants is due not only to their direct effects on target tissues but also indirectly to the actions of resident and infiltrating macrophages. These cells release an array of mediators with cytotoxic, pro- and anti-inflammatory, angiogenic, fibrogenic, and mitogenic activity, which function to fight infections, limit tissue injury, and promote wound healing. However, following exposure to toxicants, macrophages can become hyperresponsive, resulting in uncontrolled or dysregulated release of mediators that exacerbate acute tissue injury and/or promote the development of chronic diseases such as fibrosis and cancer. Evidence suggests that the diverse activity of macrophages is mediated by distinct subpopulations that develop in response to signals within their microenvironment. Understanding the precise roles of these different macrophage populations in the pathogenic response to toxicants is key to designing effective treatments for minimizing tissue damage and chronic disease and for facilitating wound repair.
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                Author and article information

                Journal
                Pharmacogn Mag
                Pharmacogn Mag
                PM
                Pharmacognosy Magazine
                Medknow Publications & Media Pvt Ltd (India )
                0973-1296
                0976-4062
                August 2014
                : 10
                : Suppl 3
                : S563-S568
                Affiliations
                [1] College of Pharmacy, Pusan National University, Busan, Korea
                [1 ] Gyeongnam Department of Environment & Toxicology, Korea Institute of Toxicology, Jegok-gil, Munsan-eup, Gyeongnam, Korea
                [2 ] College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul, Korea
                [3 ] Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju, Korea
                Author notes
                Address for correspondence: Prof. Eun Ju Jeong, Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju-660-758, Korea. E-mail: ejjeong@ 123456gntech.ac.kr
                Article
                PM-10-563
                10.4103/0973-1296.139783
                4189273
                afca7ec6-2f18-4fde-87c7-d8ac5762a609
                Copyright: © Pharmacognosy Magazine

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 April 2014
                : 09 June 2014
                : 30 August 2014
                Categories
                Original Article

                Pharmacology & Pharmaceutical medicine
                antifibrotic,hsc-t6,halophyte,limonium tetragonum,raw264.7
                Pharmacology & Pharmaceutical medicine
                antifibrotic, hsc-t6, halophyte, limonium tetragonum, raw264.7

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