title: Anti-inflammatory Effects of Ganoderma lucidum Triterpenoid in Human Crohn's Disease Associated with Downregulation of NF-κB Signaling.
abstract: BACKGROUND
  Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Current medications have potentially serious side effects. Hence, there is increasing interest in alternative therapies. We previously demonstrated the anti-inflammatory effects of Food Allergy Herbal Formula-2 in vitro on peripheral blood mononuclear cells (PBMCs) and mucosa from CD subjects. Here, we investigated the anti-inflammatory effects of a bioactive compound isolated from Ganoderma lucidum (G. lucidum), a key herbal constituent of Food Allergy Herbal Formula-2, in CD in vitro.
  
  
  METHODS
  Triterpene ganoderic acid C1 (GAC1) was isolated from G. lucidum. Stimulated RAW 264.7 macrophages were treated with GAC1. Human PBMCs and colonic biopsies were obtained from children with CD and cultured with or without GAC1. TNF-α and other proinflammatory cytokine levels were measured in the culture supernatant. NF-κB signaling was investigated in PBMCs and colonic mucosa treated with GAC1 by In-Cell Western and Western blot analysis.
  
  
  RESULTS
  GAC1 decreased TNF-α production by macrophages and PBMCs from CD subjects. GAC1 significantly decreased TNF-α, IFN-γ, and IL-17A production by inflamed colonic biopsies from CD subjects. These effects were due to downregulation of the NF-κB signaling pathway.
  
  
  CONCLUSIONS
  GAC1 inhibited production of TNF-α and other proinflammatory cytokines by PBMCs and inflamed CD colonic mucosa due to blockage of NF-κB activation. GAC1 is a key beneficial constituent in G. lucidum and the Food Allergy Herbal Formula-2 in suppressing the inflammatory cytokines found in CD and warrants clinical investigation for the treatment of CD.
authors.affiliation: *Department of Pediatrics, Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, New York; †Division of Gastroenterology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York; and ‡The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Changda
authors.initials: C
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Dunkin
authors.forename: Joanne
authors.initials: J
authors.lastname: Lai
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Clare
authors.initials: C
authors.lastname: Ceballos
authors.forename: Keith
authors.initials: K
authors.lastname: Benkov
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D002648:Child; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D020940:Reishi / Q000737:chemistry*; D015398:Signal Transduction; D014315:Triterpenes / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C556862:ganoderic acid