Table 4.
Overview of the significant gene expression changes attributed to the intervention with specific foods or derived products containing bioactive compounds and reported in different cells and tissue samples (p-value < 0.05).
| Reference | Cells 1 | Groups Compared | Potential Bioactive Compounds (Specifically Indicated in the Article) | Upregulated Genes | Downregulated Genes | Genes not Changing or with a Not Significant Change | Association with Metabolites | Effect on Protein Levels | Main biological Message Reported |
|---|---|---|---|---|---|---|---|---|---|
| Olive oil and derived products | |||||||||
| Farràs M et al., 2013 [31] | White blood cells 1 | High vs. moderate polyphenol olive oil (post-) | Olive oil polyphenols | ABCA1, SCARB1, PPARG, PPARA, PPARD, MED1, CD36, PTGS1 | - | (NC) ABCG1, PTGS2 | ↑HTyr acetate in plasma with ↑ABCA1 | NR | Enhancement of cholesterol efflux from cells |
| Konstantinidou V et al., 2010 [28] | Mononuclear cells | Med diet + olive oil (polyphenols) vs control diet (post-) |
Mix compounds present in the Med diet and the olive oil (fatty acids, polyphenols, vitamins etc.) | - | ADRB2, ARHGAP15, IL7R, POLK, IFNG | - | ↓IFNG with ↑Tyr in urine (highest dose of olive oil) | ↓ IFNγ in plasma (post- vs. pre-) | Regulation of atherosclerosis-related genes, improvement of oxidative stress and inflammatory status |
| Camargo A et al., 2010 [27] | Mononuclear cells | High vs. low polyphenol olive oil (post-) | Olive oil polyphenols | - | EGR1, IL1B | (NS↓) JUN, PTGS2 | NR | NR | Lessening of deleterious inflammatory profile |
| Castañer O et al., 2012 [30] | Mononuclear cells | High vs. low polyphenol olive oil (post-) | Olive oil polyphenols | - | CD40LG, IL23A, IL7R, CXCR2, OLR1, ADRB2, CCL2 | (NS↓) IFNG, VEGFB, ICAM1 (NC) ALOX5AP, TNFSF10 |
↓OLR1 with the ↑Tyr and ↑HTyr in urine | ↓CCL2 | Reduction of atherogenic and inflammatory processes |
| Hernáez Á et al., 2015 [34] | Mononuclear cells | High vs. low polyphenol olive oil (post-) | Olive oil polyphenols | - | - | (NS↑) LPL | NR | NR | Reduction of LDL concentrations and of LDL atherogenicity |
| Martín-Peláez S et al., 2015 [35] | Mononuclear cells | High vs. low polyphenol olive oil (post-) | Olive oil polyphenols | - | ACE, NR1H2, CXCR2 | (NS↓) CXCR1, ADRB2, MPO, ACE (NC) ECE2, OLR1 |
NR | NR | Modulation of the renin-angiotensin-aldosterone system and systolic blood pressure |
| Crespo MC et al., 2015 [63] | Mononuclear cells | Olive mill waste water extract Hytolive (enriched in HTyr) vs. placebo (post-) | Olive waste polyphenols (HTyr) | - | - | (NC) Phase II enzymes: NQO1,2, GSTA1,4, GSTK1, GSTM1-5, GSTO1,2, GSTP1, GSTM1,2, HNMT, INMT, MGST1-3 | NR | NR | Hormesis hypothesis of activation of phase II enzymes by polyphenols |
| Boss A et al., 2016 [64] | Mononuclear cells | Olive leaf extract (oleuropein, HTyr) vs. placebo (post-) | Olive leaf polyphenols (oleuropein, HTyr) | ID3 | EGR1, PTGS2 | - | NR | NR | Regulation of inflammatory and lipid metabolism pathways |
| Kruse M et al., 2015 [36] | Adipose tissue | Olive oil (MUFA) (post- vs. pre-, postpandrial) | Mix olive oil bioactive compounds | CCL2 | - | (NS↓) IL6, IL8 (NS↑) IL10, TNF (NC) IL1β, ADGRE1, SERPINE1 |
NR | (NC) MCP-1 (CCL2) | Acute inflammatory and metabolic response related genes |
| Broccoli and derived products | |||||||||
| Atwell LL et al., 2015 [25] | Blood | Broccoli sprout (SFGluc) vs. Myrosinase-treated broccoli sprout extract (SFGluc) (post- vs. pre-) |
SFGluc | - | - | (NC) CDKN1A, HMOX1 | NR | (NC) plasma levels of HMOX1 (HO-1) | Search for chemopreventive targets |
| Doss JF et al., 2016 [26] | Blood | Broccoli (SFGluc) | SFGluc | HBG1, HMOX1 | - | (NS↑) NQO1 | NR | (NC) Hbg1 or HbF | Gene expression studies in sickle cell disease (oxidative stress related) |
| Riso P et al., 2010 [24] | Mononuclear cells | Broccoli (SFGluc, Lut, β-car, VitC) (post- vs. pre-) |
SFGluc, Lut, β-car, VitC |
- | - | (NC) OGG1, NUDT1, HMOX1 | NR | NR | Antioxidant protection related to DNA repairing enzymes |
| Yanaka A et al., 2009 [23] | Polymorpho-nuclear granulocytes | Broccoli sprout (SFGluc) (post- vs. pre-) |
SFGluc | HMOX1 | - | - | NR | NR | Protective effect against bacterial infection (anti-oxidative, anti-inflammatory) |
| Gasper AV et al., 2007 [21] | Gastric antrum | Broccoli drink (containing SFGluc) (post- vs. pre-) |
SFGluc | GCLM, TXNRD1 | - | (NC) CDKN1A | NR | NR | Effect on xenobiotic metabolism |
| Riedl MA et al., 2009 [22] | Cells from nasal lavage | Broccoli sprout (SFGluc) (different doses) vs. control (alfalfa sprout) |
SFGluc | GSTM1, GSTP1, NQO1, HMOX1 | - | - | NR | NR | Effect on Phase II metabolism |
| Grape products and compounds (Res) | |||||||||
| Weseler AR et al., 2011 [49] | Blood | Flavanols isolated from grape seeds (post- vs. pre-) | Flavanols | - | IL6, TNF, IL10 | (NS↓) CAT, GSR, HMOX1 (NC) IL1β, CXCL8, NOS2, NFKBIA, ICAM1, VCAM1, GPX1, GPX4, SOD2 |
NR | Plasma: ↓TNF (NC) IL10 |
Anti-inflammatory effects in blood |
| Barona J et al., 2012 [50] | Mononuclear cells | Grape powder vs. placebo | Mix compounds in grape (flavonoids) | NOS2 (individuals without dyslipidemia) | - | (NC) CYBB, SOD1, SOD2, GPX1, GPX4 | NR | NR | Anti-oxidative and anti-inflammatory response |
| Tomé-Carneiro J et al., 2013 [51] | Mononuclear cells | Grape extract vs Grape extract + Res (post- vs. pre-) |
Polyphenols, Res | LRRFIP1 | IL1β, TNF, CCL3, NFKBIA | (NC) NFKB1 | NR | NC in TNF levels in PBMC or serum | Beneficial immune-modulatory effect |
| Nguyen AV et al., 2009 [48] | Colon tissue (cancer and normal) | Low concentration of grape powder (post- vs. pre-) | Res, flavanols, flavans, anthocyanins, catechin | Normal tissue MYC Cancer tissue MYC, CCND1 |
Normal tissue CCND1, AXIN2 |
- | NR | NR | Effect on cancer related pathway |
| Mansur AP et al., 2017 [78] | White blood cells | Res (post- vs. pre-; T vs. C) |
Res | - | - | (NC) SIRT1 | NR | ↑ Serum hSIRT1 | Comparative study with caloric restriction |
| Chachay VS et al., 2014 [76] | Mononuclear cells | Res (from Polygonium cuspidatum) | Res | - | - | (NC) NQO1, PTP1B, IL6, HMOX1 | NR | ↓plasma IL6 | Effects on non-alcoholic fatty liver disease |
| Yiu EM et al., 2015 [77] | Mononuclear cells | Res (two doses) (post- vs. pre-) | Res | - | - | (NC) FXN (dose 1) (NS↓) FXN (dose 2) |
NR | (NC) FXN in PBMC | Effect on the neurodegenerative disease (Friedreich ataxia) |
| Olesen J et al., 2014 [75] | Skeletal muscle | Res (post- vs. pre-; T vs. C) |
Res | - | - | (NC) PPARGC1A, TNF, NOS2 | NR | (NC) TNF, iNOS in muscle and plasma |
Metabolic and inflammatory status |
| Yoshino J et al., 2012 [73] | Skeletal muscle and adipose tissue | Res (post- vs. pre-; T vs. C) |
Res | - | - | (NC) SIRT1, NAMPT, PPARGC1A, UCP3 | NR | NR | Metabolic effects |
| Poulsen MM et al., 2013 [74] | Skeletal muscle and adipose tissue | Res (post- vs. pre-) | Res | - | Muscle SLC2A4 |
Muscle (NC) PPARGC1A Adipose (NC) TNF, NFKB1 |
NR | NR | Metabolic and inflammatory effects |
1 White blood cells or Leukocytes: mononuclear cells agranulocytes (lymphocytes and monocytes) and polymorphonuclear granulocytes (neutrophils, eosinophils, basophils, mast cells). Table abbreviations (in alphabetical order): β-car, β-carotene; HTyr, hydroxytyrosol; LDL, low-density lipoprotein; Lut, lutein; Med, Mediterranean; NC, no change; NR, not reported; NS, not significant; MUFA, monounsaturated fatty acids; PBMC, peripheral blood mononuclear cells; post-, after treatment; pre-, baseline or before treatment; Res, resveratrol; SFGluc, sulphoraphane glucosinolates; Tyr, tyrosol; VitC, vitamin C. Genes nomenclature from GeneCards [92] (in alphabetical order): ABCA1, ATP binding cassette subfamily A member 1; ABCG1, ATP binding cassette subfamily G member 1; ACE, angiotensin I converting enzyme; ADRB2, adrenoceptor beta 2; ADGRE1, adhesion G protein-coupled receptor E1 (alias: EMR1); ALOX5AP, arachidonate 5-lipoxygenase activating protein; ARHGAP15, rho GTPase activating protein 15; CAT, catalase; CCL2, C-C motif chemokine ligand 2 (alias: MCP-1, monocyte chemotactic protein 1); CCL3, C-C motif chemokine ligand 3; CCND1, cyclin D1; CD36, CD36 molecule; CD40LG, CD40 ligand; CDKN1A, cyclin dependent kinase inhibitor 1A (alias: p21); CXCL8, C-X-C motif chemokine ligand 8 (alias: IL8); CXCR1, C-X-C motif chemokine receptor 1; CXCR2, C-X-C motif chemokine receptor 2 (alias: IL8RA); CYBB, cytochrome B-245 beta chain (alias: NOX2, GP91-Phox); ECE2, endothelin converting enzyme 2; EGR1, early growth response 1; EMR1, FXN, frataxin, Friedreich ataxia protein; GCLC, glutamate-cysteine ligase catalytic subunit (alias: γGCL); GPX1, glutathione peroxidase 1; GPX4, glutathione peroxidase 4; GSTA1, glutathione S-transferase alpha 1; GSTA4, glutathione S-transferase alpha 4; GSTK1, glutathione S-transferase kappa 1; GSTM1, glutathione S-transferase Mu 1; GSTM2, glutathione S-transferase Mu 2; GSTM3, glutathione S-transferase Mu 3; GSTM4, glutathione S-transferase Mu 4; GSTM5, glutathione S-transferase Mu 5; GSTO1, glutathione S-transferase omega 1; GSTO2, glutathione S-transferase omega 2; GSTP1, glutathione S-transferase Pi 1; GSR, glutathione-disulfide reductase (alias: GRD1); HBG1, hemoglobin subunit gamma 1; HMOX1, heme oxygenase 1 (alias:HO-1); HNMT, histamine N-methyltransferase; ICAM1, intercellular adhesion molecule 1; ID3, inhibitor of DNA binding 3, HLH protein; IFNG, interferon gamma; IL1B, interleukin 1 beta; IL6, interleukin 6; IL7R, interleukin 7 receptor; IL8, interleukin 8; IL10, interleukin 10; IL23A, interleukin 23 subunit alpha; INMT, indolethylamine N-methyltransferase; JUN, jun proto-oncogene, AP-1 transcription factor subunit; LPL, lipoprotein lipase; LRRFIP1, LRR binding FLII interacting protein 1; MED1, mediator complex subunit 1 (alias: PPARBP); MGST1,microsomal glutathione S-transferase 1; MGST2, microsomal glutathione S-transferase 2; MGST3, microsomal glutathione S-transferase 3; MPO, myeloperoxidase; MYC, MYC proto-oncogene, BHLH transcription factor; NAMPT, nicotinamide phosphoribosyltransferase; NFKB1, nuclear factor kappa B subunit 1; NFKBIA, NFKB inhibitor alpha; NQO1, NAD(P)H quinone dehydrogenase 1; NQO2, N-ribosyldihydronicotinamide: quinone reductase 2; NOS2, nitric oxide synthase 2 (alias: iNOS); NR1H2, nuclear receptor subfamily 1 group H member 2; NUDT1, nudix hydrolase 1; OGG1, 8-oxoguanine DNA glycosylase; OLR1, oxidized low density lipoprotein receptor 1; POLK, DNA polymerase kappa; PPARA, peroxisome proliferator activated receptor alpha; PPARD, peroxisome proliferator activated receptor delta; PPARG, peroxisome proliferator activated receptor gamma; PPARGC1A, PPARG coactivator 1 alpha (alias: PGC1α); PTGS1, prostaglandin-endoperoxide synthase 1 (alias: COX1); PTGS2, prostaglandin-endoperoxide synthase 2 (alias: COX2); PTPN1, protein tyrosine phosphatase, non-receptor type 1 (alias: PTP1B); SCARB1, scavenger receptor class B member 1 (alias: SRB1); SERPINE1, Serpin Family E Member 1; SIRT1, sirtuin 1; SLC2A4, solute carrier family 2 member 4 (alias: GLUT4); SOD1, superoxide dismutase 1 (alias: Cu/ZnSOD); SOD2, superoxide dismutase 2 (alias: MnSOD); TNF, tumor necrosis factor (alias: TNFα); TNFSF10, TNF Superfamily Member 10; TXNRD1, thioredoxin reductase 1 (alias: TR1); UCP3, uncoupling protein 3; VCAM1, vascular cell adhesion molecule 1; VEGFB, vascular endothelial growth factor B. Orange color: upregulated genes; green color: downregulated genes.