title: Immunomodulatory activity of polysaccharides isolated from Alchornea cordifolia.
abstract: BACKGROUND
  Extracts of leaves from different species of the genus Alchornea have been used for centuries to treat a variety of medicinal problems in tropical Africa. However, little is known about the high-molecular weight active components conferring therapeutic properties to these extracts.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the immunomodulatory activity of polysaccharides isolated from the leaves of Alchornea cordifolia.
  
  
  METHODS
  Water-soluble polysaccharides from leaves of Alchornea cordifolia were extracted and fractionated by DEAE-cellulose, Diaion HP-20, and size-exclusion chromatography. Molecular weight, sugar analysis, and other physical and chemical characterization of the fractions were performed. Immunomodulatory activity of the polysaccharide fractions was evaluated by determining their ability to induce monocyte/macrophage nitric oxide (NO) and cytokine production. Activation of mitogen activated protein kinases (MAPK) was also assessed using a phospho-MAPK array. Activation of nuclear factor κB (NF-κB) was measured using an alkaline phosphatase reporter gene assay in THP1-Blue monocytic cells.
  
  
  RESULTS
  Six polysaccharide fractions from Alchornea cordifolia were isolated. Fractions containing type II arabinogalactan had potent immunomodulatory activity. Particularly, the parent fraction AP-AU and its high-molecular weight sub-fraction AP-AU1 (average M(r) was estimated to be 39.5kDa) induced production of NO and cytokines [interleukin (IL)-1β, -6, -10, tumor necrosis factor (TNF)-α, and granulocyte-macrophage-colony stimulating factor (GM-CSF)] in human peripheral blood mononuclear cells and human and murine monocyte/macrophages cell lines in vitro. Furthermore, treatment with AP-AU1 induced phosphorylation of Akt2, p38δ/p38γ, p70S6K1, RSK2, and mTOR, as well as stimulation of NF-κB transcriptional activity.
  
  
  CONCLUSIONS
  Our results provide a molecular basis to explain a portion of the beneficial therapeutic properties of water extracts from Alchornea cordifolia leaves in traditional folk medicine of Africa.
authors.affiliation: Laboratoire d'Endocrinologie et Biologie de la Reproduction, Université de Cocody-Abidjan, Côte d'Ivoire.
authors.forename: Koffi
authors.initials: K
authors.lastname: Kouakou
authors.forename: Igor A
authors.initials: IA
authors.lastname: Schepetkin
authors.forename: Ahoua
authors.initials: A
authors.lastname: Yapi
authors.forename: Liliya N
authors.initials: LN
authors.lastname: Kirpotina
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jutila
authors.forename: Mark T
authors.initials: MT
authors.lastname: Quinn
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D019665:Euphorbiaceae; D006801:Humans; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D016488:Medicine, African Traditional; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D016328:NF-kappa B; D010936:Plant Extracts; D011134:Polysaccharides; D009569:Nitric Oxide; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases