title: Unraveling the adipocyte inflammomodulatory pathways activated by North American ginseng.
abstract: BACKGROUND
  North American (NA) ginseng (Panax quinquefolius) is a popular natural health product (NHP) that has been demonstrated to regulate immune function, inflammatory processes and response to stress and fatigue. Recent evidence suggests that various extracts of NA ginseng may have different bioactivities because of distinct profiles of ginsenosides and polysaccharides. To date, the bioactive role of ginseng on adipocytes remains relatively unexplored.
  
  
  OBJECTIVE
  The goal of this work was to study the extract-specific bioactivity of NA ginseng on differentiated preadipocyte gene expression and adipocytokine secretion.
  
  
  METHODS
  In vitro differentiated 3T3-L1 preadipocytes were treated with 25 and 50 μg ml of either crude ethanol (EtOH) or aqueous (AQ) NA ginseng extracts, or polysaccharide and ginsenoside extracts isolated from the AQ extract. Global gene expression was studied with microarrays and the resulting data were analyzed with functional pathway analysis. Adipocytokine secretion was also measured in media.
  
  
  RESULTS
  Pathway analysis indicated that the AQ extract, and in particular the polysaccharide extract, triggered a global inflammomodulatory response in differentiated preadipocytes. Specifically, the expression of Il-6 (interleukin 6), Ccl5 (chemokine (C-C motif) ligand 5), Nfκb (nuclear factor-kappaB) and Tnfα (tumor necrosis factor alpha) was increased. These effects were also reflected at the protein level through the increased secretion of IL-6 and CCL5. No effect was seen with the EtOH extract or ginsenoside extract. Using a specific toll-like receptor 4 (TLR4) inhibitor reduced the upregulation of inflammatory gene expression, indicating the relevance of this pathway for the signaling capacity of NA ginseng polysaccharides.
  
  
  CONCLUSIONS
  This work emphasizes the distinct bioactivities of different ginseng extracts on differentiated preadipocyte signaling pathways, and highlights the importance of TLR4 for mediating the inflammomodulatory role of ginseng polysaccharides.
authors.affiliation: Department of Human Health and Nutritional Sciences, The University of Guelph, Guelph, Ontario, Canada.
authors.forename: S A F
authors.initials: SA
authors.lastname: Wilson
authors.forename: M H T
authors.initials: MH
authors.lastname: Wong
authors.forename: C
authors.initials: C
authors.lastname: Stryjecki
authors.forename: A
authors.initials: A
authors.lastname: De Boer
authors.forename: E M K
authors.initials: EM
authors.lastname: Lui
authors.forename: D M
authors.initials: DM
authors.lastname: Mutch
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018925:Chemokines; D015850:Interleukin-6; D052002:NF-kappa B p50 Subunit; C079995:Panax quinquefolium saponin; D010936:Plant Extracts; D011134:Polysaccharides; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; C073701:Nfkb1 protein, mouse; D000431:Ethanol