title: Bupleurum polysaccharides attenuates lipopolysaccharide-induced inflammation via modulating Toll-like receptor 4 signaling.
abstract: BACKGROUND
  Bupleurum polysaccharides (BPs), isolated from Bupleurum smithii var. parvifolium, possesses immunomodulatory activity, particularly on inflammation. Bacterial endotoxin lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor 4 (TLR4) on host cell membrane. The present study was performed to evaluate whether the therapeutic efficacy of BPs on suppression of LPS's pathogenecity could be associated with the modulating of TLR4 signaling pathway.
  
  
  RESULTS
  LPS stimulated expression and activation of factors in the TLR4 signaling system, including TLR4, CD14, IRAK4, TRAF6, NF-κB, and JNK, determined using immunocytochemical and/or Western blot assays. BPs significantly inhibited these effects of LPS. LPS increased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12p40, and IFN-β) and NO production, evaluated using ELISA and Griess reaction assays, respectively. BPs antagonized these effects of LPS. Interestingly, BPs alone augmented secretion of some pro-inflammatory cytokines of non-LPS stimulated macrophages and enhanced phagocytic activity towards fluorescent E.coli bioparticles. In a rat model of acute lung injury (ALI) with pulmonary hemorrhage and inflammation, BPs ameliorated lung injuries and suppressed TLR4 expression.
  
  
  CONCLUSIONS
  The therapeutic properties of BPs in alleviating inflammatory diseases could be attributed to its inhibitory effect on LPS-mediated TLR4 signaling.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Yun-Yi
authors.initials: YY
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Dao-Feng
authors.initials: DF
authors.lastname: Chen
mesh_terms: D000818:Animals; D029972:Bupleurum / Q000737:chemistry*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D048670:MAP Kinase Kinase 4 / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D048029:TNF Receptor-Associated Factor 6 / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011134:Polysaccharides; D048029:TNF Receptor-Associated Factor 6; C493487:Tlr4 protein, mouse; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D053592:Interleukin-1 Receptor-Associated Kinases; C507774:Irak4 protein, mouse; D048670:MAP Kinase Kinase 4