title: Emodin-6-O-β-D-glucoside inhibits HMGB1-induced inflammatory responses in vitro and in vivo.
abstract: High mobility group box 1 (HMGB1) protein acts as a potent proinflammatory cytokine and is involved in the pathogenesis of several vascular diseases, such as, systemic vasculitis and sepsis. Emodin-6-O-β-D-glucoside (EG) is a new active compound from Reynoutria japonica, and its biologic activities have not been previously investigated. In this study, we first investigated the antiinflammatory activities of EG on HMGB1-mediated proinflammatory responses in human umbilical vein endothelial cells (HUVECs) and in a murine cecal ligation and puncture (CLP)-model of sepsis in mice. EG was found to suppress the release of HMGB1, the production of tumor necrosis factor (TNF)-α, and the activation of nuclear factor-κB (NF-κB) by HMGB1 in HUVECs, and to inhibit HMGB1-mediated hyperpermeability and leukocyte migration in mice. In the CLP model, HMGB1 was highly released, but this release was prevented by EG. Furthermore, EG also increased the survival times of CLP administered mice. Collectively, this study shows EG can protect barrier integrity and inhibit HMGB1-mediated inflammatory responses, which suggests a potential use as a therapy for sepsis or septic shock.
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, School of Medicine, Kyungpook National University, 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: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002432:Cecum / Q000601:surgery; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004195:Disease Models, Animal; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000009:adverse effects* / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008026:Ligation; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000401:mortality; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005960:Glucosides; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C583240:emodin-6-O-glucoside; D004642:Emodin