title: Antiseptic effect of vicenin-2 and scolymoside from Cyclopia subternata (honeybush) in response to HMGB1 as a late sepsis mediator in vitro and in vivo.
abstract: Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, which are 2 active compounds from C. subternata that act against high mobility group box 1 (HMGB1)-mediated septic responses in human umbilical vein endothelial cells (HUVECs) and mice. The antiseptic activities of vicenin-2 and scolymoside were determined by measuring permeability, neutrophil adhesion and migration, and activation of proinflammatory proteins in HMGB1-activated HUVECs and mice. According to the results, vicenin-2 and scolymoside effectively inhibited lipopolysaccharide-induced release of HMGB1, and suppressed HMGB1-mediated septic responses such as hyperpermeability, the adhesion and migration of leukocytes, and the expression of cell adhesion molecules. In addition, vicenin-2 and 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 HMGB1. Collectively, these results indicate that vicenin-2 and scolymoside could be a potential therapeutic agents for the treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
authors.affiliation: a College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu 702-701, Republic of Korea.|b 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: a College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu 702-701, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Yoon
authors.affiliation: c Division of Plant Biosciences, School of Applied BioSciences, College of Agriculture and Life Science, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: d Department of Ophthalmology, School of Medicine, Kyungpook National University, 50 Samduk-dong-2-ga, Jung-gu, Daegu 700-721, Republic of Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Park
authors.affiliation: a College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu 702-701, Republic of Korea.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047310:Apigenin / Q000302:isolation & purification / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D053998:Cyclopia Plant / Q000737:chemistry; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D047311:Luteolin / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy; D010946:Plants, Medicinal; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000891:Anti-Infective Agents, Local; D000893:Anti-Inflammatory Agents; D005960:Glucosides; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C530449:apigenin-6,8-di-C-glycopyranoside; C440499:lipopolysaccharide, Escherichia coli O111 B4; C458139:scolymoside; D047310:Apigenin; D047311:Luteolin
keywords: HMGB1; inflammation; scolymoside; sepsie; sepsis; vicenin-2; vicenine-2