title: Inhibitory effects of epi-sesamin on endothelial protein C receptor shedding in vitro and in vivo.
abstract: OBJECTIVE
  Endothelial protein C receptor (EPCR) plays a pivotal role in augmenting Protein C activation by the thrombin-thrombomodulin complex. The activity of EPCR is markedly changed by ectodomain cleavage and release as the soluble protein (sEPCR). The EPCR shedding is mediated by the tumor necrosis factor-α converting enzyme (TACE). Epi-sesamin (ESM), from the roots of Asarum siebodlii, is known to exhibit anti-allergic and anti-fungal activities. However, little is known about the effects of ESM on EPCR shedding.
  
  
  METHODS
  We investigated this issue by monitoring the effects of ESM on phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and cecal ligation and puncture (CLP)-mediated EPCR shedding.
  
  
  RESULTS
  Data showed that ESM induced potent inhibition of PMA, TNF-α, IL-1β, and CLP-induced EPCR shedding, likely through suppression of TACE expression. In addition, treatment with ESM resulted in a reduction of PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK).
  
  
  CONCLUSIONS
  Given these results, ESM should be viewed as a candidate therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of EPCR shedding.
authors.affiliation: Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.forename: Hayoung
authors.initials: H
authors.lastname: Yoo
authors.forename: Chang-Kyun
authors.initials: CK
authors.lastname: Han
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism*; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology*; D000074283:Endothelial Protein C Receptor; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D004149:Dioxoles; D000074283:Endothelial Protein C Receptor; D053583:Interleukin-1beta; D017705:Lignans; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; C054125:sesamin