title: Forsythoside B protects against experimental sepsis by modulating inflammatory factors.
abstract: The present study investigated the effects of Forsythoside B on an experimental model of sepsis induced by caecal ligation and puncture (CLP) in rats and elucidated the potential mechanism in cultured RAW 264.7 cells. Results showed that Forsythoside B concentration-dependently down-regulated the levels of TNF-α, IL-6 and high-mobility group-box 1 protein (HMGB1) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, inhibited the IκB kinase (IKK) pathway and modulated nuclear factor (NF)- κB. Intravenous injection (i.v.) of Forsythoside B alone or plus Imipenem reduced serum levels of TNF-α, IL-6, HMGB1, triggering receptor expressed on myeloid cells (TREM-1) and endotoxin, while the serum level of IL-10 was up-regulated and myeloperoxidase (MPO) in lung, liver and small intestine was reduced. Meanwhile, i.v. of Forsythoside B alone or plus Imipenem reduced CLP-induced lethality in rats. These data indicated that the antisepsis effect of Forsythoside B is mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. Its antisepsis mechanism may be that Forsythoside B binds to LPS and reduces the biological activity of serum LPS, and inhibits NF-κB activition. Our studies enhance the case for the use of Forsythoside B in sepsis. Forsythoside B itself has promise as a therapy for the treatment of sepsis in humans.
authors.affiliation: College of Pharmacy and Institute of Material Medica, Binzhou Medical University, Yantai, PR China.
authors.forename: Wang-Lin
authors.initials: WL
authors.lastname: Jiang
authors.lastname: Yong-Xu
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Zhang
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Zhu
authors.lastname: Jian-Hou
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D005960:Glucosides / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D015378:Imipenem / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D005960:Glucosides; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011971:Receptors, Immunologic; C547511:TREM1 protein, rat; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; C552409:forsythoside B; D016753:Interleukin-10; D015378:Imipenem; D009195:Peroxidase; D051550:I-kappa B Kinase