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      Phyllostachys edulis Compounds Inhibit Palmitic Acid-Induced Monocyte Chemoattractant Protein 1 (MCP-1) Production

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          Abstract

          Background

          Phyllostachys edulis Carriere (Poaceae) is a bamboo species that is part of the traditional Chinese medicine pharmacopoeia. Compounds and extracts from this species have shown potential applications towards several diseases. One of many complications found in obesity and diabetes is the link between elevated circulatory free fatty acids (FFAs) and chronic inflammation. This study aims to present a possible application of P. edulis extract in relieving inflammation caused by FFAs. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is a pro-inflammatory cytokine implicated in chronic inflammation. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1) are transcription factors activated in response to inflammatory stimuli, and upregulate pro-inflammatory cytokines such as MCP-1. This study examines the effect of P. edulis extract on cellular production of MCP-1 and on the NF-κB and AP-1 pathways in response to treatment with palmitic acid (PA), a FFA.

          Methodology/Principal Findings

          MCP-1 protein was measured by cytometric bead assay. NF-κB and AP-1 nuclear localization was detected by colorimetric DNA-binding ELISA. Relative MCP-1 mRNA was measured by real-time quantitative PCR. Murine cells were treated with PA to induce inflammation. PA increased expression of MCP-1 mRNA and protein, and increased nuclear localization of NF-κB and AP-1. Adding bamboo extract (BEX) inhibited the effects of PA, reduced MCP-1 production, and inhibited nuclear translocation of NF-κB and AP-1 subunits. Compounds isolated from BEX inhibited MCP-1 secretion with different potencies.

          Conclusions/Significance

          PA induced MCP-1 production in murine adipose, muscle, and liver cells. BEX ameliorated PA-induced production of MCP-1 by inhibiting nuclear translocation of NF-κB and AP-1. Two O-methylated flavones were isolated from BEX with functional effects on MCP-1 production. These results may represent a possible therapeutic application of BEX and its compounds toward alleviating chronic inflammation caused by elevated circulatory FFAs.

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          Most cited references45

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          MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.

          Adipocytes secrete a variety of bioactive molecules that affect the insulin sensitivity of other tissues. We now show that the abundance of monocyte chemoattractant protein-1 (MCP-1) mRNA in adipose tissue and the plasma concentration of MCP-1 were increased both in genetically obese diabetic (db/db) mice and in WT mice with obesity induced by a high-fat diet. Mice engineered to express an MCP-1 transgene in adipose tissue under the control of the aP2 gene promoter exhibited insulin resistance, macrophage infiltration into adipose tissue, and increased hepatic triglyceride content. Furthermore, insulin resistance, hepatic steatosis, and macrophage accumulation in adipose tissue induced by a high-fat diet were reduced extensively in MCP-1 homozygous KO mice compared with WT animals. Finally, acute expression of a dominant-negative mutant of MCP-1 ameliorated insulin resistance in db/db mice and in WT mice fed a high-fat diet. These findings suggest that an increase in MCP-1 expression in adipose tissue contributes to the macrophage infiltration into this tissue, insulin resistance, and hepatic steatosis associated with obesity in mice.
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            The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer.

            Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.
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              AP-1 function and regulation.

              AP-1 (activating protein-1) is a collective term referring to dimeric transcription factors composed of Jun, Fos or ATF (activating transcription factor) subunits that bind to a common DNA site, the AP-1-binding site. As the complexity of our knowledge of AP-1 factors has increased, our understanding of their physiological function has decreased. This trend, however, is beginning to be reversed due to the recent studies of gene-knockout mice and cell lines deficient in specific AP-1 components. Such studies suggest that different AP-1 factors may regulate different target genes and thus execute distinct biological functions. Also, the involvement of AP-1 factors in functions such as cell proliferation and survival has been made somewhat clearer as a result of such studies. In addition, there has been considerable progress in understanding some of the mechanisms and signaling pathways involved in the regulation of AP-1 activity. In addition to regulation by heterodimerization between Jun, Fos and ATF proteins, AP-1 activity is regulated through interactions with specific protein kinases and a variety of transcriptional coactivators.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                18 September 2012
                27 September 2012
                : 7
                : 9
                : e45082
                Affiliations
                [1 ]Department of Cell and Molecular Biology, University of Hawaii John A. Burns School of Medicine, Honolulu, Hawaii, United States of America
                [2 ]Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii, United States of America
                University of Leuven, Rega Institute, Belgium
                Author notes

                Competing Interests: The authors maintain that there is no conflict of interest with regards to the cited patent (Chinese invention patent, CN1287848A). The patent belongs to Golden Basin Bio-Tech, and we have no ownership of their patent. The bamboo extract used in this study was donated to us by Golden Basin. We have no ownership or financial investment in Golden Basin, nor are receiving any remuneration or compensation from Golden Basin for our studies. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: JKH JP. Performed the experiments: JKH ZL. Analyzed the data: JKH ZL. Contributed reagents/materials/analysis tools: PW JP. Wrote the paper: JKH JP.

                Article
                PONE-D-12-04402
                10.1371/journal.pone.0045082
                3445604
                23028772
                0b714211-bc41-478b-86ac-8a38af2cde85
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 February 2012
                : 17 August 2012
                Page count
                Pages: 11
                Funding
                This work was supported by grants R21 AT003874 (Panee) and R21 AT005139 (Panee) from the National Center for Complementary and Alternative Medicine (NCCAM); grant U54RR022762 (RTRN Small Grant Program) from the National Center for Research Resources; grants from the National Center for Research Resources (5 G12 RR003061) and the National Institute on Minority Health and Health Disparities (8 G12 MD007601) from the National Institutes of Health; grants from the National Center for Research Resources (5P20RR016467-11) and the National Institute of General Medical Sciences (8 P20 GMl 03466-11) from the National Institutes of Health; and grant 5P20 MD000173-08 from National Center on Minority Health and Health Disparities (NCMHD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biochemistry
                Lipids
                Fatty Acids
                Drug Discovery
                Immunology
                Immune System
                Cytokines
                Immunity
                Inflammation
                Molecular Cell Biology
                Signal Transduction
                Signaling in Cellular Processes
                Chemistry
                Phytochemistry
                Phytochemicals
                Phytopharmacology
                Medicine
                Clinical Immunology
                Immune System
                Cytokines
                Immunity
                Inflammation
                Complementary and Alternative Medicine
                Drugs and Devices
                Drug Research and Development
                Drug Discovery
                Nutrition
                Obesity

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                Uncategorized

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