A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity- and Cancer-Related Genes in Whole Blood of Humans

J Nutr. 2015 Nov;145(11):2448-55. doi: 10.3945/jn.115.215392. Epub 2015 Sep 30.

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.

Conclusion: 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.

Keywords: Mono Mac 6; cancer; garlic; gene expression; immunity.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral*
  • Aryl Hydrocarbon Receptor Nuclear Translocator / blood
  • Aryl Hydrocarbon Receptor Nuclear Translocator / genetics
  • B-Lymphocytes / immunology*
  • Basic Helix-Loop-Helix Transcription Factors / blood
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Line
  • Cross-Over Studies
  • Female
  • Garlic*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / blood
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Male
  • Membrane Proteins / blood
  • Membrane Proteins / genetics
  • Middle Aged
  • Oncostatin M / blood
  • Oncostatin M / genetics
  • Proto-Oncogene Proteins c-jun / blood
  • Proto-Oncogene Proteins c-jun / genetics
  • RNA, Messenger / blood
  • RNA, Messenger / metabolism
  • Receptors, Aryl Hydrocarbon / blood
  • Receptors, Aryl Hydrocarbon / genetics
  • T-Lymphocytes / immunology*
  • Transcription Factor RelA / blood
  • Transcription Factor RelA / genetics
  • Up-Regulation

Substances

  • AHR protein, human
  • ARNT protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Membrane Proteins
  • NFAM1 protein, human
  • OSM protein, human
  • Proto-Oncogene Proteins c-jun
  • RELA protein, human
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Transcription Factor RelA
  • Oncostatin M
  • Aryl Hydrocarbon Receptor Nuclear Translocator

Associated data

  • ClinicalTrials.gov/NCT01293591