title: The ginger component 6-shogaol prevents TNF-α-induced barrier loss via inhibition of PI3K/Akt and NF-κB signaling.
abstract: Anti-inflammatory properties of the ginger-derived pungent component 6-shogaol (6-SG) have been studied intensively in recent years. Purpose of this study was to characterize the influence of 6-SG on inflammation-related intestinal barrier dysfunction, especially its paracellular component.
  
  
  
  The effect of 6-SG was studied in the human intestinal cell models HT-29/B6 and Caco-2 either under control conditions or challenged by the pro-inflammatory cytokine tumor necrosis factor α (TNF-α). Electrophysiological measurements, freeze-fracture electron microscopy, and protein analyses were performed. 6-SG partially prevented both, the TNF-α-induced decrease in transepithelial resistance and the rise in fluorescein permeability. By inhibiting phosphatidylinositol-3-kinase/Akt signaling 6-SG prevented the TNF-α-induced increase in protein expression of claudin-2, a channel-forming tight junction protein. In addition, the TNF-α-induced disassembly of the sealing tight junction protein claudin-1 was attenuated, the latter of which was due to TNF-α-triggered phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB).
  
  
  
  6-SG has barrier-protective effects by affecting TNF-α-induced claudin-2 upregulation and claudin-1 disassembly via inhibition of phoshatidylinositol-3-kinase/Akt and nuclear factor kappa light chain enhancer of activated B-cell signaling. Therefore, 6-SG-containing food might be beneficial for barrier preservation during intestinal inflammation.
authors.affiliation: Nutritional Medicine and Clinical Physiology, Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Luettig
authors.affiliation: Nutritional Medicine and Clinical Physiology, Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Rosenthal
authors.affiliation: Nutritional Medicine and Clinical Physiology, Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: In-Fah M
authors.initials: IM
authors.lastname: Lee
authors.affiliation: Nutritional Medicine and Clinical Physiology, Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Krug
authors.affiliation: Nutritional Medicine and Clinical Physiology, Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Schulzke
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000378:metabolism; D018938:Caco-2 Cells; D002396:Catechols / Q000494:pharmacology*; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism; D057167:Claudins / Q000235:genetics / Q000378:metabolism; D020939:Zingiber officinale / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; C568108:CLDN1 protein, human; C491875:CLDN2 protein, human; D002396:Catechols; D062445:Claudin-1; D057167:Claudins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C040115:shogaol; D019869:Phosphatidylinositol 3-Kinases
keywords: 6-Shogaol; Ginger; Intestinal barrier; TNF-α; Tight junction