Table 1.
Summary of the most relevant effects of flavanol and flavanol-rich product treatments on immunity, inflammation and metabolism in cultured cells a.
| Reference | Cellular Model | Flavanol/Food | Concentration | Duration | Main Outcomes |
|---|---|---|---|---|---|
| [68] | HAEC cells + 25 mM glucose | EGCG | 1 µM | 72 h | ↓monocyte adhesion to HAEC, ↓NF-κB. |
| [69] | THP-1 cells (human monocytes) + 25 mM glucose | EC | 5 µM | 24 h | ↓TNF-α, ↓NF-κB, ↓acetyl CBP/p300, ↓HDAC4, ↓H3K9ac/H3, ↓H3K4m2/H3, ↑H3K9me2/H3 |
| [72] | PBMC (from 20 obese volunteers) induced with PMA | Red grape polyphenolic extract | 1, 3, 5 µg/mL | 24 h (co-treatment) | ↓IL-21, ↓IL-1β, ↓IL-6, =IL-17, =TNF-α, ↑IL-10, =IFN-γ, =IL-4, =IL-2 |
| [73] | Macrophages LPS-induced (U937 monocytes) | GPE | 0, 30, 60, 100 µg/mL | 4 h (GPE, 1 h + 100 ng/mL LPS, 3 h) | ↓TNF-α, ↓IL-6, ↓IL-1β, ↓IL-8, ↓IP-10, ↓MCP-1, ↓COX-2, ↓JNK, ↓p38, ↓NF-κB, ↓cJun, ↓Elk-1, ↑IκBα |
| [73] | Adipocytes (abdominal WAT from obese volunteers) induced with macrophage-conditioned media | GPE | 0, 30, 60, 100 µg/mL | 4 h (GPE, 1 h + 100 ng/mL LPS, 3 h) | ↓IL-6, ↓IL-8, ↓MCP-1, ↓IL-1β, ↓NF-κB, ↓glucose uptake in adipocytes |
| [74] | Human white differentiated adipocytes+RAW264 macrophages (co-culture) | Oligomerized grape seed polyphenols | 10, 20 µg/mL | 24 h | ↓TNF-α, ↓MCP-1, ↓PAI-1, ↓ERK, ↓NF-κB, ↓ROS, =FFA release |
| [75]. | Mouse 3T3L1 differentiated adipocytes + RAW264.7 macrophages (co-culture) | Theflavin-3,3′-digallate | 0, 25, 50 µM | 48 h | ↓NO; ↓TNF-α, ↓IL-1β, ↓IL-6, ↓MCP-1, ↓iNOS, ↓CCR7, ↓CD86, ↓CD80, ↑IL-10, ↑CD206, ↑CD163, ↑arginase-1 ↑PPAR-γ, ↓p-IKK, ↓p-IκB, ↓p-p65-NF-κB, ↓COX-2, ↓p-STAT3, ↓ROS, ↓TG, ↓NEFA, ↓FAS, ↓glycerol, ↑ adiponectin, ↑AMPK. |
| [76] | RAW264.7 macrophages (1 µg/mL LPS) | CAE | 31–500 µg/mL | 24 h | ↓NO, ↓PGE2, ↓TNF-α, ↓MCP-1, ↓IL-6, ↓ROS. |
| [76] | Mouse 3T3L1 adipocytes (conditioned media) | CAE | 31–500 µg/mL | 24 h | ↓TNF-α, ↓MCP-1, ↓IL-6, ↓TG, ↓lipid content, ↑glycerol release, ↑lipase activity, ↑adiponectin, ↑mitochondrial function and content, ↑PGC-1α, ↑UCP-1, ↑glucose uptake, ↑GLUT-4 translocation, ↑IR, ↑PI3K, ↑AKT. |
| [77] | PBMC (12 lean + 12 obese, sex-matched) | EGCG | 20 µM | 24 h | ↓NF-κB, ↑Fox3p-positive Tregs, ↑IL-10, ↑HDCA2 in Tregs and HDAC activity. |
| [78] | PBMC (obeses receiving grape powder for 9 weeks) LPS-stimulated (1 µg/L) | Grape powder | 23 g (2×/day, 3.79 mg PP/day) | 24, 48 and 72 h | ↑IL-1β, ↑IL-6, =IL-8. |
| [79] | Mouse 3T3L1 differentiated adipocytes + RAW264.7 macrophages (co-culture) | GTE+ citrus PMFs+ lychee polyphenols | 10–100 µg/mL | 24 h | ↓IL-6, ↓IL-1β, ↓iNOS, ↑p21, ↑p53, ↑AMPK, ↑cyclinE1, ↓CDK2, ↓proliferation, ↓differentiation, ↓C/EBPs, ↓PPARγ. |
| [80] | Mouse 3T3L1 differentiated adipocytes (5 ng/mL TNF-α, co-treatment) | GC-(4→8)-GCG | 10, 20 µg/mL | 24 h | ↓MCP-1, ↓IL-6, ↓COX-2, ↓TG, ↓lipid content, ↓epididymal, ↓PPARγ, ↓SREBP-1c, ↓C/EBPα, ↓p-JNK, =ERK, ↓p-p38↓p-STAT3, ↓p-IκB, ↑IκB, ↓p-p65-NF-κB |
a The arrow indicates an increase (↑) or decrease (↓) in the level or activity of the different parameters analyzed, “=” symbol designates unchanged parameters. AKT/PKB: protein kinase B; AMPK: adenine monophosphate activated protein kinase; CAE: cocoa shell aqueous phenolic extract; CCR7: C-C chemokine receptor type 7; C/EBPα: CCAAT/enhancer-binding protein alpha; CDK2: cyclin-dependent kinase 2; COX-2: cyclooxygenase-2; EC: epicatechin; EGCG: epigallocatechin gallate; Elk1: ETS Like-1 protein; ERK: extracellular signal-regulated kinase; FAS: fatty acid synthase; FFA: free fatty acid; Fox3p: forkhead box p3 transcription factor; GC-(4→8)-GCG: gallocatechin-(4→8)-gallocatechin-3-O-gallate; GLUT: glucose transporter; GPE: polyphenol-rich grape powder extract; GTE: green tea extract; HAEC: human aortic endothelial cells; HDCA: histone deacetylase; H3K9ac: histone H3 lysine 9 acetylation; H3K4me2: histone H3 lysine 4 dimethylation; H3K9me2: histone H3 lysine 9 dimethylation; IFN-γ: interferon-γ; IκB: inhibitor κB; IKK: IκB kinase; IL: interleukin; iNOS: inducible nitric oxide synthase; IP-10: interferon-γ inducible protein-10; IR: insulin receptor; JNK: c-Jun NH2-terminal kinase; LPS: lipopolysaccharide; MAPK: mitogen activated protein kinases; MCP-1: monocyte chemotactic protein-1; NEFA: non-esterified fatty acid; NF-κB: nuclear factor-kappa B; NO: nitric oxide; p38: p38-MAPK; PAI-1: plasminogen activator inhibitor-1; PBMC: peripheral blood mononuclear cells; PGC-1α: Peroxisome proliferator-activated receptor-gamma coactivator-1α; PGE2: protastglandin E2; PI3K: phosphatidylinositol 3-kinase; PMA: phorbol myristate acetate; PMFs: polymethoxyflavones; PP: polyphenol; PPAR: Peroxisome proliferator activated receptor; ROS: reactive oxygen species; SREBP: sterol regulatory element-binding protein; STAT: signal transducer and activator of transcription; TG: triglycerides; TNF-α: tumor necrosis factor α; Treg: regulatory T cells; UCP: uncoupling protein; WAT: white adipose tissue.