Charron Craig S, Dawson Harry D, Albaugh George P, Solverson Patrick M, Vinyard Bryan T, Solano-Aguilar Gloria I, Molokin Aleksey, Novotny Janet A
Beltsville Human Nutrition Research Center and.
Biometrical Consulting Services, USDA, Agricultural Research Service, Beltsville, MD.
J Nutr. 2015 Nov;145(11):2448-55. doi: 10.3945/jn.115.215392. Epub 2015 Sep 30.
Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease.
We designed a study to probe the mechanisms of garlic action in humans.
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.
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.
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.
临床前和流行病学研究表明,摄入大蒜与癌症和心血管疾病的进展呈负相关。
我们设计了一项研究来探究大蒜对人体的作用机制。
我们进行了一项随机交叉喂养试验,17名志愿者在食用10天的控制饮食(不含大蒜)后,食用含大蒜餐(100克白面包、15克黄油和5克生蒜末)或不含大蒜的对照餐(100克白面包和15克黄油)。在食用测试餐后0小时和3小时采集血液,用于全血基因表达分析。使用Illumina BeadArray筛选感兴趣的基因,随后对选定基因进行实时定量逆转录聚合酶链反应(qRT-PCR)。为了补充人体研究结果,用纯化的大蒜提取物(0.5μL/mL)处理单核细胞增多性李斯特菌6细胞,并在0、3、6和24小时通过qRT-PCR测量mRNA。
发现以下7个基因因摄入大蒜而上调:芳烃受体(AHR)、芳烃受体核转运体(ARNT)、缺氧诱导因子1α(HIF1A)、原癌基因c-Jun(JUN)、活化T细胞核因子(NFAT)激活蛋白免疫受体酪氨酸基活化基序1(NFAM1)、抑瘤素M(OSM)和V-rel禽网状内皮组织增生病毒癌基因同源物(REL)。mRNA转录本的增加倍数范围为1.6(HIF1A)至3.0(NFAM1)(P<0.05)。在人体试验中上调的7个基因中的5个基因的mRNA水平在细胞培养的3小时和6小时也上调:AHR、HIF1A、JUN、OSM和REL。细胞培养中mRNA转录本的增加倍数范围为1.7(HIF1A)至12.1(JUN)(P<0.01)。通过ELISA测量OSM蛋白,在3、6和24小时时显著高于对照(24小时时:对照和大蒜组分别为19.5±1.4和74.8±1.4 pg/mL)。OSM是一种多效细胞因子,可抑制培养中的几种肿瘤细胞系。
这些数据表明,大蒜的生物活性是多方面的,包括激活与人类和单核细胞增多性李斯特菌6细胞中的免疫、凋亡和外源性物质代谢相关的基因。该试验已在clinicaltrials.gov上注册,注册号为NCT01293591。