title: A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity- and Cancer-Related Genes in Whole Blood of Humans.
abstract: BACKGROUND
  Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease.
  
  
  OBJECTIVE
  We designed a study to probe the mechanisms of garlic action in humans.
  
  
  METHODS
  We conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15 g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was collected before and 3 h after test meal consumption for gene expression analysis in whole blood. Illumina BeadArray was used to screen for genes of interest, followed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6 cells were treated with a purified garlic extract (0.5 μL/mL), and mRNA was measured by qRT-PCR at 0, 3, 6, and 24 h.
  
  
  RESULTS
  The following 7 genes were found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1α (HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1), oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog (REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1) (P < 0.05). The mRNA levels of 5 of the 7 genes that were upregulated in the human trial were also upregulated in cell culture at 3 and 6 h: AHR, HIF1A, JUN, OSM, and REL. Fold-increases in mRNA transcripts in cell culture ranged from 1.7 (HIF1A) to 12.1 (JUN) (P < 0.01). OSM protein was measured by ELISA and was significantly higher than the control at 3, 6, and 24 h (24 h: 19.5 ± 1.4 and 74.8 ± 1.4 pg/mL for control and garlic, respectively). OSM is a pleiotropic cytokine that inhibits several tumor cell lines in culture.
  
  
  CONCLUSIONS
  These data indicate that the bioactivity of garlic is multifaceted and includes activation of genes related to immunity, apoptosis, and xenobiotic metabolism in humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as NCT01293591.
authors.affiliation: Beltsville Human Nutrition Research Center and.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Charron
authors.affiliation: Beltsville Human Nutrition Research Center and.
authors.forename: Harry D
authors.initials: HD
authors.lastname: Dawson
authors.affiliation: Beltsville Human Nutrition Research Center and.
authors.forename: George P
authors.initials: GP
authors.lastname: Albaugh
authors.affiliation: Beltsville Human Nutrition Research Center and.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Solverson
authors.affiliation: Biometrical Consulting Services, USDA, Agricultural Research Service, Beltsville, MD.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Vinyard
authors.affiliation: Beltsville Human Nutrition Research Center and.
authors.forename: Gloria I
authors.initials: GI
authors.lastname: Solano-Aguilar
authors.affiliation: Beltsville Human Nutrition Research Center and.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Molokin
authors.affiliation: Beltsville Human Nutrition Research Center and janet.novotny@ars.usda.gov.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Novotny
mesh_terms: D000284:Administration, Oral; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000097:blood / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood / Q000235:genetics; D002460:Cell Line; D018592:Cross-Over Studies; D005260:Female; D005737:Garlic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D053683:Oncostatin M / Q000097:blood / Q000235:genetics; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000097:blood / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D051996:Transcription Factor RelA / Q000097:blood / Q000235:genetics; D015854:Up-Regulation
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D053683:Oncostatin M; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D051996:Transcription Factor RelA; C111235:AHR protein, human; C497396:ARNT protein, human; C497442:HIF1A protein, human; C000715470:MAS1 protein, human; C475087:NFAM1 protein, human; C508351:OSM protein, human; C498143:RELA protein, human
keywords: Mono Mac 6; cancer; garlic; gene expression; immunity