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. 2014 Feb 21;6(2):844–880. doi: 10.3390/nu6020844

Table 2.

In vitro studies on cocoa polyphenol CVD-related anti-inflammatory activities. Ref. = Reference.

Model Treatment (dose) Outcomes Ref.
Leukotrienes
(a) Isolated rabbit 15-LOX-1 (a) Cocoa procyanidins: monomers to decamers (2.9 mg/mL) Dose-dependent: (a) ↓15-LOX-1 activity [215]
(b) Recombinant human platelet 12-LOX (b) Epicatechin & procyanidin decamers (b) ↓12-LOX activity
Recombinant human 5-LOX Cocoa epicatechin & procyanidins ↓5-LOX activity [216]
(10 μmol/L) ↓Pro-inflammatory mediators (LTB4, LTC4, LTD4)
Pro-Inflammatory and Anti-Inflammatory Cytokines
PHA-stimulated PBMC Cocoa procyanidins: monomers through decamers (25 μg/mL) ↓IL-1β secretion (monomer to tetramer) [217]
↑IL-1β secretion (pentamer to decamer)
↓IL-2 expression (pentamer to heptamer)
↓IL-4 expression & secretion (pentamer to decamer)
Human PBMC Cocoa procyanidins: monomers through decamers (25 μg/mL) ↑IL-1β transcription & secretion (pentamers-decamers) [218]
↓IL-1β transcription & secretion (monomers-tetramers)
Resting and (PHA)-stimulated human PBMC Cocoa procyanidins: monomers through decamers (25 μg/mL) Resting PBMCs: [219]
↑IL-4 secretion (hexamer-decamer fraction)
PHA-stimulated PBMCs:
↑IL-4 secretion (monomeric fraction)
↓IL-4 secretion (hexamer-decamer fraction)
Resting and (PHA)-stimulated human PBMC CFP fractions: monomers through decamers (25 μg/mL) ↓ TNF-α (monomers and dimers) [220]
↑ TNF-α (tetramers through octamers)
PHA-stimulated PBMC Cocoa flavanols and their related oligomers (25 μg/mL) ↓ IL-5 release (oligomeric fractions: hexamers to decamers) [221]
Rat NR8383 macrophages Cocoa polyphenol extract (10–50 μg/mL tot. PPh) vs. epicatechin (30–60 μg/mL tot. PPh) ↓ TNF-α, MCP-1, IL-1α, IL-6) [222]
Murine EL4BOU6 lymphocytes Cocoa extract (5–80 μg/mL tot. PPh) vs. epicatechin (60–120 μg/mL tot. PPh) ↓IL-2 secretion [223]
↑IL-4 secretion
↓T lymphocyte activation
Human PBMC Cocoa flavanol fractions: Short (monomers-pentamers) ↑IL-1β, IL-6, IL-10, TNF-α (long-chain fraction) [224]
Long-chain (hexamers-decamers) (20 μg/mL)
LPS-stimulated human PBMC Cocoa phenolic acids: (3,4-DHPPA, 3-HPA, ↓TNF-α [225]
3,4-DHPAA, 3-HPAA, ↓IL-6
4-HBA) (1 µM) ↑IL-1β
NF-κB Activity
Jurkat T cells Purified cocoa: [(−)-epicatechin (EC) and ↓NF-κB [226]
(+)-catechin (CT)] and a B dimeric procyanidin (DP-B) (1.7–17.2 µM) ↓IL-2 transactivation

4-DHPAA—3,4-dihydroxyphenylacetic acid; 3,4-DHPPA—3,4 dihydroxyphenylpropionic acid; 3-HPA—3-hydroxyphenylpropionic acid; 3-HPAA—3-hydroxyphenylacetic acid; 4-HBA—4-hydroxybenzoic acid; CFP—Cocoa flavanols preparation; LOX—lipoxygenase; MCP-1—monocyte chemoattractant protein-1; PBMC—peripheral blood mononuclear cells; PHA—phytohemagglutinin; VSMC—vascular smooth muscle cells.