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Cyanidin-3-O-Glucoside Ameliorates Lipopolysaccharide-Induced Injury Both In Vivo and In Vitro Suppression of NF-κB and MAPK Pathways

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Abstract

Cyanidin-3-O-glucoside (C3G), an anthocyanin belonging to the flavonoid family and commonly present in food and vegetables in human diet, has exhibited anti-inflammatory and anti-oxidant effects. This study aimed to investigate the protective ability of C3G against inflammatory and oxidative injuries, as well as to clarify the possible mechanism in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) in vitro and acute respiratory distress syndrome mouse model in vivo. HUVECs or male Kunming mice were pretreated with C3G 1 h before LPS stimulation. C3G significantly inhibited the production of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL) -6, and IL-1β) in cell supernatants and bronchoalveolar lavage fluid (BALF) as determined by enzyme-linked immunosorbent assay. Histopathologic examination with hematoxylin and eosinstaining showed that C3G pretreatment substantially suppressed inflammatory cell infiltration, alveolar wall thickening, and interstitial edemain lung tissues. C3G markedly prevented LPS-induced elevation of malondialdehyde and myeloperoxidase levels in lung tissue homogenates, wet to dry ratio of lung tissues, total cells, and inflammatory cells (neutrophils and macrophages) in BALF. Moreover, C3G reduced superoxide dismutase activity in the lung tissue homogenates. Western blot assay also showed that C3G pretreatment significantly suppressed LPS-induced activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by blocking the phosphorylation of inhibitor κB-α, NF-κB/P65, extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase in the lung tissues. In summary, C3G may ameliorate LPS-induced injury, which results from inflammation and oxidation, by inhibiting NF-κB and MAPK pathways and playing important anti-inflammatory and anti-oxidative roles.

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Acknowledgments

This work has received funding from the Natural Science Foundation of Shandong Province, (ZR2014HM112 and ZR2014HL004), the Science and Technology Development Plan of Shandong Province (2011GSF11830), and Taishan Scholar project of Shandong Province.

Conflict of Interest

None of the authors of this study has any financial or commercial conflicts of interest.

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    Authors and Affiliations

    1. Department of Respirator Medicine and Intensive Care Unit, Affiliated Hospital of Binzhou Medical University, Binzhou, 256603, Shandong Province, China

      Ming-Ming Ma, Yan Li, Wei-Wei Zhu, Gui-Qing Kong, Xiao Huang, Li-Peng Wang & Xiao-Zhi Wang

    2. Department of Cell Biology, Binzhou Medical University, Yantai, 264003, Shandong Province, China

      Xiang-Yong Liu

    3. Pediatric Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou, 256603, Shandong Province, China

      Xiang Ren

    4. Cell Morphology Room, Affiliated Hospital of Binzhou Medical University, Binzhou, 256603, Shandong Province, China

      Li-Qing Luo

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    1. Ming-Ming Ma
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    Correspondence to Xiang-Yong Liu or Xiao-Zhi Wang.

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    Ming-Ming Ma and Yan Li contributed equally to this work.

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    Ma, MM., Li, Y., Liu, XY. et al. Cyanidin-3-O-Glucoside Ameliorates Lipopolysaccharide-Induced Injury Both In Vivo and In Vitro Suppression of NF-κB and MAPK Pathways. Inflammation 38, 1669–1682 (2015). https://doi.org/10.1007/s10753-015-0144-y

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