title: Emodin-6-O-β-D-glucoside down-regulates endothelial protein C receptor shedding.
abstract: Endothelial protein C receptor (EPCR) plays an important role in the protein C anticoagulation pathway and in the cytoprotective pathway. Previously, EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). Soluble EPCR levels are increased in patients with systemic inflammatory diseases. Recently, we reported that a new active compound, emodin-6-O-β-D-glucoside (EG) from Reynoutria japonica, has anti-inflammatory activities. However, little is known of the effects of EG on EPCR shedding. Here, we investigated this issue by monitoring the effects of EG on the phorbol-12-myristate 13-acetate (PMA) or the cecal ligation and puncture (CLP)-mediated EPCR shedding and its underlying mechanisms. Data showed that EG potently inhibited the PMA and CLP-induced EPCR shedding by suppressing TACE expression. Given these results, EG could be used as a candidate therapeutic for the treatment of vascular inflammatory diseases.
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Republic of Korea.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D004642:Emodin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D011956:Receptors, Cell Surface / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D018805:Sepsis / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; D005960:Glucosides; C478370:PROCR protein, human; C080248:Procr protein, mouse; D011956:Receptors, Cell Surface; C583240:emodin-6-O-glucoside; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse; D004642:Emodin