title: Ameliorative Effect of Vicenin-2 and Scolymoside on TGFBIp-Induced Septic Responses.
abstract: Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-β. TGFBIp is released by the human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, two active compounds in C. subternata against TGFBIp-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of vicenin-2 or scolymoside were determined by measuring permeability, human neutrophils adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated HUVECs and mice. According to the results, vicenin-2 or scolymoside effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, vicenin-2 or scolymoside suppressed the production of tumor necrosis factor-α and interleukin 6 and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by TGFBIp. Vicenin-2 or scolymoside reduced cecal ligation and puncture (CLP)-induced septic mortality and pulmonary injury. Collectively, these results indicate that vicenin-2 and scolymoside could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway.
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu, 702-701, Republic of Korea.|Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu, 702-701, Republic of Korea.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu, 702-701, Republic of Korea. baejs@knu.ac.kr.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D047310:Apigenin / Q000302:isolation & purification / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D053998:Cyclopia Plant / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins / Q000276:immunology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D047311:Luteolin / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011654:Pulmonary Edema / Q000276:immunology / Q000517:prevention & control; D018805:Sepsis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D000099222:betaIG-H3 Protein
chemical_list: D000893:Anti-Inflammatory Agents; D047310:Apigenin; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D005960:Glucosides; D018836:Inflammation Mediators; D047311:Luteolin; D010936:Plant Extracts; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C530449:apigenin-6,8-di-C-glycopyranoside; C458139:scolymoside
keywords: HUVEC; TGFBIp; inflammation; scolymoside; sepsis; vicenin-2