title: Eugenosedin-A prevents high-fat diet increased adhesion molecules through inhibition of MAPK- and p65-mediated NF-κB pathway in rat model.
abstract: OBJECTIVE
  Previous studies have shown eugenosedin-A, a 5-HT(1B/2A) and α(1)/α(2)/β(1)-adrenergic blocker, is able to decrease cholesterol levels, hyperglycaemia and inflammation in hyperlipidaemic mice induced by high-fat diet (HFD). The aim of this study is to examine the effects of eugenosedin-A on the inhibition of adhesion molecules of platelets, the aorta and acyl-coenzymeA:cholesterol acyltransferase-1 (ACAT-1) of macrophages in a hyperlipidaemic rat model.
  
  
  METHODS
  Six-week-old Sprague-Dawley rats were randomly divided into two control and treatment groups. The control rats received either a regular diet or HFD and the treatment groups were fed HFD with either 5 mg/kg eugenosedin-A or atorvastatin for a 10-week period.
  
  
  RESULTS
  Compared with the two control groups, the HFD group had lower levels of high-density lipoprotein, higher concentrations of triglycerides, total cholesterol, low-density lipoprotein and insulin. The expression of adhesion molecules in platelets, aorta and monocyte-macrophage were enhanced by HFD. HFD also increased upstream proteins and their phosphorylated form in the aorta. In treatment groups, eugenosedin-A and atorvastatin improved HFD-induced hyperlipidaemia and levels of insulin. Eugenosedin-A reduced the upregulation of P-selectin, ICAM-1, ICAM-2, ICAM-3, VCAM, PECAM in platelets and inhibited E-selectin, ICAM-1, ICAM-2, ICAM-3, VCAM and PECAM protein levels in the aorta. Eugenosedin-A reduced the ACAT-1 protein expression of monocyte-macrophages. The expression of PKCα, MAPKs, IKKα and p65 and their phosphorylated form were reduced in treatment groups.
  
  
  CONCLUSIONS
  Taken together, hyperlipidaemia enhances the expression of adhesion molecules and ACAT-1 protein, and eugenosedin-A ameliorates those increases. Through inhibition of MAPK- and p-65-mediated NF-κB pathway, eugenosedin-A decreases the quantity of adhesion molecules.
authors.affiliation: Department of Food Science and Nutrition, Meiho University, Pingtung, Taiwan.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Lin
authors.forename: Kuo-Ping
authors.initials: KP
authors.lastname: Shen
authors.forename: Wen-Tsan
authors.initials: WT
authors.lastname: Chang
authors.forename: Jou-Chun
authors.initials: JC
authors.lastname: Lin
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: D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D010879:Piperazines; C498145:Rela protein, rat; D051996:Transcription Factor RelA; C496985:eugenosedin-A; D000101:Acetyl-CoA C-Acetyltransferase; D020929:Mitogen-Activated Protein Kinase Kinases