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      Ganoderma lucidum Polysaccharides Reduce Lipopolysaccharide-Induced Interleukin-1 β Expression in Cultured Smooth Muscle Cells and in Thoracic Aortas in Mice

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          Abstract

          The expression of inflammatory cytokines on vascular walls is a critical event in vascular diseases and inflammation. The aim of the present study was to examine the effects of an extract of Ganoderma lucidum (Reishi) polysaccharides (EORPs), which is effective against immunological disorders, on interleukin- (IL-) 1 β expression by human aortic smooth muscle cells (HASMCs) and the underlying mechanism. The lipopolysaccharide- (LPS-) induced IL-1 β expression was significantly reduced when HASMCs were pretreated with EORP by Western blot and immunofluorescent staining. Pretreatment with 10  μ g/mL EORP decreased LPS-induced ERK, p38, JNK, and Akt phosphorylation. But the increase in IL-1 β expression with LPS treatment was only inhibited by pretreatment with the ERK1/2 inhibitor, while the JNK and p38 inhibitors had no effect. In addition, EORP reduced the phosphorylation and nuclear translocation of nuclear factor- (NF-) κ B p65 in LPS-treated HASMCs. Furthermore, in vivo, IL-1 β expression was strongly expressed in thoracic aortas in LPS-treated mice. Oral administration of EORP decreased IL-1 β expression. The level of IL-1 β expression in LPS-treated or in LPS/EORP-treated group was very low and was similar to that of the saline-treated group in toll-like receptor 4-deficient (TLR4 −/−) mice. These findings suggest that EORP has the anti-inflammatory property and could prove useful in the prevention of vascular diseases and inflammatory responses.

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          MAPK signalling in cardiovascular health and disease: molecular mechanisms and therapeutic targets.

          Intracellular MAPK (mitogen-activated protein kinase) signalling cascades probably play an important role in the pathogenesis of cardiac and vascular disease. A substantial amount of basic science research has defined many of the details of MAPK pathway organization and activation, but the role of individual signalling proteins in the pathogenesis of various cardiovascular diseases is still being elucidated. In the present review, the role of the MAPKs ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase) and p38 MAPK in cardiac hypertrophy, cardiac remodelling after myocardial infarction, atherosclerosis and vascular restenosis will be examined, with attention paid to genetically modified murine model systems and to the use of pharmacological inhibitors of protein kinases. Despite the complexities of this field of research, attractive targets for pharmacological therapy are emerging.
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            Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum.

            Ganoderma lucidum is a popular medicinal mushroom, which has been used in the Traditional Chinese medicine for the prevention or treatment of a variety of diseases. In the present study we evaluated the anti-inflammatory effects of the triterpene extract from G. lucidum (GLT) in LPS-stimulated macrophages. Here we show that GLT markedly suppressed the secretion of inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and inflammatory mediator nitric oxide (NO) and prostaglandin E(2) (PGE(2)) from lipopolysaccharide (LPS)-stimulated murine RAW264.7 cells. GLT also down-regulated LPS-dependent expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in RAW264.7 cells. The anti-inflammatory effects of GLT were mediated by the inhibition of transcription factor NF-kappaB as demonstrated by decreased NF-kappaB-DNA binding activity, and the suppression of p65 phosphorylation in LPS-stimulated macrophages treated with GLT. Moreover, GLT inhibited LPS-dependent AP-1-DNA binding activity and down-regulated expression of AP-1 subunit c-Jun. In addition, GLT suppressed the activity of MAP kinases as observed by the down-regulation of LPS-induced phosphorylation of ERK1/2 and JNK but not p38. In vivo experiments clearly demonstrated that GLT also inhibited the production of TNF-alpha and IL-6 in LPS-induced endotoxemic mice. Apart from its anti-inflammatory activity, GLT suppressed cell proliferation of RAW264.7 cells through cell cycle arrest at G0/G1-G2M, which was mediated by the down-regulation of expression of cell cycle regulatory proteins cyclin D1, CDK4 and cyclin B1, respectively. In conclusion, the anti-inflammatory and anti-proliferative effects of GLT on macrophages are mediated through the inhibition of NF-kappaB and AP-1 signaling pathways.
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              Novel antioxidant peptides from fermented mushroom Ganoderma lucidum.

              Oxidative stress has been linked with the pathogenesis of many human diseases including cancer, aging, and atherosclerosis. The present study investigates the antioxidant activities of peptides isolated from the medicinal mushroom, Ganoderma lucidum. G. lucidum has been shown to possess potent antioxidant activity with little or no side effects. Polysaccharide, polysaccharide-peptide complex, and phenolic components of G. lucidum have been proposed to be responsible for this antioxidant effect. However, research has shown that the G. lucidum peptide (GLP) is the major antioxidant component of G. lucidum. The objective of this study was to evaluate the antioxidant activity of this peptide using different oxidation systems. GLP showed potent antioxidant activities in both lightproof soybean oil and lard systems, assessed by lipid peroxidant value. Compared to butylated hydroxytoluene, GLP showed a higher antioxidant activity in the soybean oil system. Soybean lipoxygenase activity was blocked by GLP in a dose-dependent manner with an IC50 value of 27.1 microg/mL. GLP showed scavenging activity toward hydroxyl radicals produced in a deoxyribose system with an IC50 value of 25 microg/mL, and GLP effectively quenched superoxide radical anion produced by pyrogallol autoxidation in a dose-dependent manner. Malondialdehyde level has been used as the oxidation index in many biological systems. GLP showed substantial antioxidant activity in the rat liver tissue homogenates and mitochondrial membrane peroxidation systems. The auto-hemolysis of rat red blood cells was also blocked by GLP in a dose-dependent manner. On the basis of these results, it is concluded that GLP is the major constituent responsible for the antioxidant activity of G. lucidum. GLP could play an important role in the inhibition of lipid peroxidation in biological systems through its antioxidant, metal chelating, and free radical scavenging activities. Copyright 2004 American Chemical Society
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi Publishing Corporation
                1741-427X
                1741-4288
                2014
                4 March 2014
                4 March 2014
                : 2014
                : 305149
                Affiliations
                1Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Ren-Ai Road, Taipei 100, Taiwan
                2Department of Nursing, Division of Basic Medical Sciences, Chiayi Campus, Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 303, Taiwan
                3Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
                4Graduate Institute of Integrated Medicine, China Medical University, Taichung 404, Taiwan
                5Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung 404, Taiwan
                6Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei 112, Taiwan
                7Department of Obstetrics and Gynecology, Hsinchu Cathay General Hospital, Hsinchu 300, Taiwan
                8Institute of Clinical Medical Science, China Medical University, No. 91 Hsueh-Shih Road, Taichung 404, Taiwan
                Author notes

                Academic Editor: Xingjiang Xiong

                Author information
                http://orcid.org/0000-0002-7619-1902
                http://orcid.org/0000-0002-6498-4008
                Article
                10.1155/2014/305149
                3960732
                24723958
                bfa8b68c-fdb6-4587-8421-c62603214920
                Copyright © 2014 Chan-Jung Liang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 November 2013
                : 7 January 2014
                : 28 January 2014
                Funding
                Funded by: http://dx.doi.org/10.13039/501100001868 National Science Council Taiwan
                Award ID: NSC 99-2320-B-002-022-MY3
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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