title: Inhibitory effects of astragalin on lipopolysaccharide-induced inflammatory response in mouse mammary epithelial cells.
abstract: BACKGROUND
  Tea brewed from the leaves of persimmon or Rosa agrestis have several medical functions including treating allergy, antiatopic dermatitis, and anti-inflammatory effects. The objective of this study was to investigate the molecular mechanisms of astragalin, a main flavonoid component isolated from these herbs, in modifying lipopolysaccharide (LPS)-induced signaling pathways in primary cultured mouse mammary epithelial cells (mMECs).
  
  
  METHODS
  The mMECs were treated with LPS in the absence or presence of different concentrations of astragalin. The expression of proinflammatory cytokines tumor necrosis factor α, and interleukin 6, as well as nitric oxide production were determined by enzyme-linked immunosorbent assay and Griess reaction, respectively. Cyclooxygenase-2, inducible nitric oxide synthase, toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), inhibitor protein of NF-κB (IκBα), P38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase were measured by Western blot.
  
  
  RESULTS
  The results showed that astragalin suppressed the expression of tumor necrosis factor α, interleukin 6, and nitric oxide in a dose-dependent manner in mMECs. Western blot results showed that the expression of inducible nitric oxide synthase and cyclooxygenase-2 was inhibited by astragalin. Besides, astragalin efficiently decreased LPS-induced TLR4 expression, NF-κB activation, IκBα degradation, and the phosphorylation of p38, extracellular signal-regulated kinase in BMECs.
  
  
  CONCLUSIONS
  Our results indicated that astragalin exerts anti-inflammatory properties possibly via the inactivation of TLR4-mediated NF-κB and mitogen-activated protein kinases signaling pathways in LPS-stimulated mMECs. Thus, astragalin may be a potential therapeutic agent for bovine mastitis.
authors: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
authors: Fengyang
authors: F
authors: Li
authors: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
authors: Wei
authors: W
authors: Wang
authors: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
authors: Yongguo
authors: Y
authors: Cao
authors: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
authors: Dejie
authors: D
authors: Liang
authors: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
authors: Wenlong
authors: W
authors: Zhang
authors: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
authors: Zecai
authors: Z
authors: Zhang
authors: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
authors: Haichao
authors: H
authors: Jiang
authors: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China.
authors: Mengyao
authors: M
authors: Guo
authors: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, People's Republic of China. Electronic address: zhangns@jlu.edu.cn.
authors: Naisheng
authors: N
authors: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D029788:Diospyros / Q000737:chemistry; D004347:Drug Interactions; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D044949:Kaempferols / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008413:Mastitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D028321:Plant Preparations / Q000737:chemistry / Q000494:pharmacology*; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D044949:Kaempferols; D008070:Lipopolysaccharides; D028321:Plant Preparations; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; C082161:lipopolysaccharide A; D009569:Nitric Oxide; C001579:astragalin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Astragalin; Cytokine; LPS; Mastitis; NF-κB; TLR4