Table 2.

In vitro and cell-culture studies performed with cocoa polyphenols.

Cell type	Treatment	Outcomes	Reference
Human LDL	Cocoa powder extract (5 μmol/L GAE°) vs. pure catechin (5 μmol/L)	LDL oxidation ↓	[26]
Liposomes & human LDL	Cocoa catechin monomers & procyanidin fractions (0.1–10.0 μg/mL)	LDL oxidation ↓	[27]
LDL	220 mL cocoa drink (cocoa concentration: 1.5, 2.0, 2.5, 3.0, 3.5%)	LDL oxidation ↓ dose-dependent	[28]
LDL	Catechin, epicatechin, procyanidin B2, procyanidin C1, cinnamtannin A2 (0.125, 0.25, 0.5, 1.0, 2.0 μg/mL)	LDL oxidizability ↓	[29]
Human LDL & VLDL	Dark chocolate, cocoa, milk chocolate, hot cocoa mixes (126, 224, 52.2, 8.2 μmol/g total phenols)	Lag time of LDL & VLDL oxidation ↑	[30]
LDL & VLDL	Dark chocolate & cocoa powder (containing fat or defatted) vs. cocoa butter	LDL & VLDL oxidizability ↓	[49]
Rat liver microsomes	Cacao liquor	NADPH-dependent lipid peroxidation ↓ Linoleic acid autoxidation ↓	[33]
Recombinant human 5-LOX	Cocoa epicatechin & procyanidins (10 μmol/L)	5-LOX activity ↓ Proinflammatory mediators (LTB4, LTC4, LTD4) ↓	[32]
Isolated rabbit 15-LOX-1 Recombinant human platelet 12-LOX	Cocoa procyanidins (monomers through decamers; 2.9 mg/mL) Epicatechin & procyanidin decamer	15-LOX-1 activity ↓ dose-dependent 12-LOX activity ↓ dose-dependent	[31]
Human PBMC *	Cocoa procyanidins (monomers through decamers; 25 μg/mL)	IL-1β secretion ↑ IL-2 expression ↓ IL-4 expression & secretion ↓	[34]
Human PBMC *	Cocoa procyanidins (monomers through decamers; 25 μg/mL)	IL-1β transcription & secretion ↑ (pentamers-decamers) IL-1β transcription & secretion ↓ (monomers-tetramers)	[36]
Human PBMC *	Cocoa procyanidins (monomers through decamers; 25 μg/mL)	Secretory IL-4 ↑	[35]
Human PBMC *	Cocoa procyanidins (monomers through decamers; 25 μg/mL)	TNF-α secretion ↑	[37]
Human PBMC *	Cocoa procyanidins (monomers through decamers; 25 μg/mL)	IL-5 secretion ↑ (monomers-trimers) IL-5 secretion ↓ (hexamers-decamers)	[38]
Human PBMC°	Short- (monomers-pentamers) & long-chain (hexamers-decamers) flavanol fractions (20 μg/mL)	Inflammatory mediators (IL-1β, IL-6, IL-10, TNF-α) ↑	[53]
Whole blood	Purified trimeric & pentameric cocoa procyanidins (3, 10 μmol/L)	PAC-1 binding & P-selectin expression ↑ in unstimulated platelets Epinephrine-induced platelet activation ↓	[54]
Isolated rabbit aortic rings	Procyanidin-rich cocoa extracts	Endothelium-dependent relaxation ↑ NOS activity ↑	[45]
ACE from rabbit lung	Epicatechin, dimeric & hexameric procyanidins (0–500 μmol/L)	ACE activity ↓ molecular weight-dependent	[47]
Murine EL4BOU6 lymphocytes	Cocoa extract (5–80 μg/mL total polyphenols) vs. epicatechin (60–120 μg/mL total polyphenols)	IL-2 secretion ↓ IL-4 secretion↑ T lymphocyte activation ↓	[41]
Murine RAW264.7 macrophages # Rat NR8383 macrophages #	Cocoa extract (5–100 μg/mL total polyphenols) vs. epicatechin (60–120 μg/mL total polyphenols) Cocoa extract (10–50 μg/mL total polyphenols) vs. epicatechin (30–60 μg/mL total polyphenols)	inducible NO ↓ Proinflammatory mediators (TNF-α, MCP-1, IL-1α, IL-6) ↓	[42]
Jurkat T cells	Catechin, epicatechin & B-type oligomers (1.7–17.2 μmol/L)	PMA-induced NF-κB activation ↓ IL-2 expression & secretion ↓	[55]
VSMC	Cocoa procyanidins (0–100 μg/mL) & procyanidin B2 (0–100 μmol/L)	MMP-2 expression & activation ↓ VSMC invasion & migration ↓ MT1-MMP & MEk1 activities ↓	[46]
HUVEC	Epicatechin & flavanol metabolites mixture vs. control	Arginase-2 mRNA expression ↓ Arginase activity ↓ dose-dependent	[44]

GAE gallic acid equivalents,

° PBMC, peripheral blood mononuclear cells;

^*,phytohemagglutinin (PHA)-stimulated;

#, lipopolysaccharide (LPS)-stimulated; MCP-1, monocyte chemoattractant protein-1;

†, 12-O-tetradecaoylphorbol-13-acetate (TPA)-stimulated; LOX, lipoxygenase; COX-2, cyclooxygenase-2; VSMC, vascular smooth muscle cells; MMP, matrix metalloproteinase; MT1, membrane type-1; MEK, mitogen-activated protein kinase kinase; HUVEC, human umbilical endothelial cells.