Abstract
CPS-F, a polysaccharide derived from Cordyceps sinensis, is a potential anti-inflammatory and anti-oxidative agent. We demonstrated that CPS-F not only inhibits platelet-derived growth factor BB (PDGF-BB)-induced intracellular reactive oxygen species (ROS) generation, and up-regulation of tumor necrosis factor-α (TNF-α), TNF-α receptor 1 (TNFR1), and monocyte chemotactic protein-1 (MCP-1), but also acts synergistically in combination with MAPK/ERK inhibitor U0126 and PI3K/Akt inhibitor LY294002. Additionally, up-regulation of pro-inflammatory factors was reversed by use of a combination of CPS-F and NADPH oxidase (NOX) inhibitor diphenyleneiodonium chloride (DPI) or silencing of NOX1. Furthermore, CPS-F prevents the PDGF receptor β (PDGFRβ) promoter activity induced by PDGF-BB in transfected cells and ameliorates increased levels of TNF-α, TNFR1, and MCP-1 when PDGFRβ is silenced, thereby suggesting that CPS-F possesses a bidirectional regulatory function. Our findings suggest CPS-F may exert its therapeutic effect for the treatment of glomerulonephritis related to human mesangial cells (HMCs) through the ERK1/2/Akt pathways.
Keywords:
Cordyceps sinensis; Inflammation; NADPH oxidase; Polysaccharide; Reactive oxygen species.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology*
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Antioxidants / chemistry
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Antioxidants / pharmacology*
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Becaplermin
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Butadienes / pharmacology
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Cell Line
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism
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Chromones / pharmacology
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Cordyceps / chemistry*
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Fungal Polysaccharides / chemistry
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Fungal Polysaccharides / pharmacology*
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Humans
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Mesangial Cells / drug effects*
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Mesangial Cells / metabolism
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Morpholines / pharmacology
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NADPH Oxidase 1
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NADPH Oxidases / genetics
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NADPH Oxidases / metabolism
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Nitriles / pharmacology
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Onium Compounds / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins c-sis / metabolism*
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Reactive Oxygen Species / metabolism
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents
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Antioxidants
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Butadienes
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CCL2 protein, human
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Chemokine CCL2
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Chromones
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Fungal Polysaccharides
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Morpholines
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Nitriles
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Onium Compounds
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-sis
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Reactive Oxygen Species
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Receptors, Tumor Necrosis Factor
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Tumor Necrosis Factor-alpha
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U 0126
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Becaplermin
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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diphenyleneiodonium
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NADPH Oxidase 1
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NADPH Oxidases
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NOX1 protein, human