title: Suppression of inflammatory response and endothelial nitric oxide synthase downregulation in hyperlipidaemic C57BL/6J mice by eugenosedin-A.
abstract: OBJECTIVE
  Eugenosedin-A has been found to ameliorate high-fat diet (HFD)-induced hyperglycaemia and hyperlipidaemia in C57BL/6J mice. This study aimed to investigate the mechanisms of action of eugenosedin-A on endothelial function and inflammation in hyperlipidaemic mice.
  
  
  METHODS
  C57BL/6J mice were randomly divided into two control groups and two treatment groups. The control mice received either a regular diet or HFD, and the treatment groups were fed HFD with either 5 mg/kg eugenosedin-A or atorvastatin for eight weeks.
  
  
  RESULTS
  Mice fed a HFD had higher concentrations of nitrate (NO) but not prostaglandin E2 (PGE2), increased tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) mRNA and inducible nitric oxide synthase (iNOS) proteins, but decreased endothelial nitric oxide synthase (eNOS) proteins. HFD-induced upregulation of iNOS is associated with p38, extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), PI3K and Akt/IKKα/p65. Eugenosedin-A and atorvastatin reduced HFD-induced TNF-α and IFN-γ mRNA, NO generation, upregulation of iNOS protein, and down-regulation of eNOS protein. Both agents inhibited p38, ERK, JNK and Akt/IKKα/p65 protein levels in the aorta. However, eugenosedin-A did not significantly reduce p38 in the liver.
  
  
  CONCLUSIONS
  Our results showed an association between obesity-induced inflammation and altered levels of TNF-α, IFN-γ, p38, ERK, JNK and Akt/IKKα/p65. Eugenosedin-A, like atorvastatin, could inhibit p38, ERK, JNK, Akt/IKKα/p65 proteins, as well as TNF-α and IFN-γ mRNA during the regulation of the obesity-induced inflammatory process.
authors.affiliation: Department of Early Childhood Care and Education, Meiho Institute of Technology, Pingtung, Taiwan.
authors.forename: Kuo-Ping
authors.initials: KP
authors.lastname: Shen
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Lin
authors.forename: Wen-Tsan
authors.initials: WT
authors.lastname: Chang
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: An
authors.forename: Ing-Jun
authors.initials: IJ
authors.lastname: Chen
authors.forename: Bin-Nan
authors.initials: BN
authors.lastname: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D000069059:Atorvastatin; D004041:Dietary Fats / Q000009:adverse effects; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009765:Obesity / Q000150:complications; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004041:Dietary Fats; D006538:Heptanoic Acids; D010879:Piperazines; D011758:Pyrroles; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C496985:eugenosedin-A; D009569:Nitric Oxide; D007371:Interferon-gamma; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III; D020928:Mitogen-Activated Protein Kinases