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.

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.

• Authors: Craig S Charron, Harry D Dawson, George P Albaugh, Patrick M Solverson, Bryan T Vinyard, Gloria I Solano-Aguilar, Aleksey Molokin, Janet A Novotny
• Journal: The Journal of nutrition (J Nutr) Vol. 145 Issue 11 Pg. 2448-55 (Nov 2015) ISSN: 1541-6100 [Electronic] United States
• PMID: 26423732 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015 American Society for Nutrition.

Chemical References

• AHR protein, human
• ARNT protein, human
• Basic Helix-Loop-Helix Transcription Factors
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• MAS1 protein, human
• Membrane Proteins
• NFAM1 protein, human
• OSM protein, human
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-jun
• RELA protein, human
• RNA, Messenger
• Receptors, Aryl Hydrocarbon
• Transcription Factor RelA
• Oncostatin M
• Aryl Hydrocarbon Receptor Nuclear Translocator

Topics

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