title: Immuno-stimulatory activity of a polysaccharide-enriched fraction of Sutherlandia frutescens occurs by the toll-like receptor-4 signaling pathway.
abstract: BACKGROUND
  Sutherlandia frutescens (L.) R. Br. is an indigenous plant of southern Africa that has been traditionally used for various cancers, infections, and inflammatory conditions.
  
  
  OBJECTIVE
  Our aim was to investigate the potential immuno-stimulatory activity of a polysaccharide-enriched fraction (SFPS) from a decoction of S. frutescens.
  
  
  METHODS
  RAW 264.7 cells (a murine macrophage cell line) were used to determine the activities of SFPS on macrophage function. The production of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines were evaluated in the cells treated with or without SFPS. CLI-095, a toll-like receptor (TLR) 4-specific inhibitor, was used to identify whether or not SFPS exerts its effects through TLR4. An antagonist of endotoxin, polymyxin B, was used to evaluate whether endotoxin present in SFPS contributed to its immune-stimulatory activity.
  
  
  RESULTS
  SFPS exhibited potent immune-stimulatory activity by macrophages. The production of ROS, NO, and tumor necrosis factor (TNF-α) were increased upon exposure to SFPS in a dose-dependent manner. All of these activities were completely blocked by co-treatment with CLI-095, but only partially diminished by polymyxin B.
  
  
  CONCLUSIONS
  We demonstrate for the first time potent immune-stimulatory activity in a decoction prepared from S. frutescens. We believe that this immune stimulatory activity is due, in part, to the action of polysaccharides present in the decoction that acts by way of TLR4 receptors and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. These findings provide a plausible mechanism through which we can understand some of the medicinal properties of S. frutescens.
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Browning
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Peggy A
authors.initials: PA
authors.lastname: Eichen
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Chi-Hua
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Valeri V
authors.initials: VV
authors.lastname: Mossine
authors.affiliation: Veterinary Medical Diagnostic Laboratory, University of Missouri, Columbia, MO 65211, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Rottinghaus
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Folk
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Lubahn
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA. Electronic address: FritscheK@missouri.edu.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Fritsche
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D007887:Fabaceae / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D016488:Medicine, African Traditional; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology*; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D010936:Plant Extracts; D011134:Polysaccharides; D017382:Reactive Oxygen Species; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide
keywords: Endotoxin; Macrophage; Polysaccharides; Sutherlandia frutescens; Toll-like receptor 4