Review Article

Polyphenols and Oxidative Stress in Atherosclerosis-Related Ischemic Heart Disease and Stroke

Table 1

Mechanisms of polyphenols in preventing atherosclerosis formation.

Pathology of atherosclerosisPolyphenols/polyphenol-rich foodPreventing mechanismReference

Endothelial dysfunctionHydroxytyrosol and EVOO polyphenol extract↑ eNOS phosphorylation, ↑ NO
↓ ET-1 synthesis
↓ ROS
[107]
High- versus low-dose flavonoid dark chocolate (213 mg versus 46 mg procyanidins)↑ endothelium-dependent flow-mediated dilation of the brachial artery
↑ plasma epicatechin concentrations
↔ LDL oxidation, total antioxidant capacity, 8-isoprostanes, blood pressure, lipid parameters, body weight, or body mass index
[108]
Red wines and grapes↑ NO activity
↑ cGMP
⊕ vascular smooth muscle relaxation
[109]

OxLDLRed wine⊝ copper-catalyzed oxidation of LDL[116]
(−)-Epicatechin gallate-enriched Hibiscus sabdariffa leaf polyphenols↓ OxLDL-dependent apoptosis[117]
Green tea catechinsIncorporated into LDL particles in nonconjugated forms
↓ oxidizability of LDL
[118]

VSMC proliferation
Red wine⊝ inhibition of PDGF β receptor
↓ VSMC proliferation and migration
[122]
Pterostilbene, polyphenol compound in blueberries↓ VSMC migration
⊝ MMP-2 activation via Erk1/2 phosphorylation
[124]
Resveratrol↑ serum BDNF concentrations
↓ VSMC contractility via a NOS-3-independent mechanism
[125]
Curcumin↓ expression of p47phox
⊝ expression of IL-6 and TNF-α
↓ iNOS activity, ↓ NO
⊝ VSMC proliferation
↑ PPARγ activity
⊝ oxidative stress
↓ AngII-induced inflammatory responses
[126]

Monocyte/macrophage and T lymphocytes inflammatory processTea flavonoids (theaflavin digallate, theaflavin, epigallocatechin gallate, epigallocatechin, and gallic acid)↓ cell-mediated LDL oxidation
↓ macrophages release superoxide and iron ions
[33]
Pomegranate juice⊝ acrolein increases macrophage lipid accumulation and alters the gut microbiota composition[129]
Ellagic acid⊝ tautomerase activity of human macrophage MIF
⊝ NF-κB nuclear translocation
[130]
Polyphenol-rich extract↓ MCP-1
↓ macrophage MIF
[132]
Resveratrol, isorhamnetin, curcumin, vanillic acid, and specific (poly)phenol mixtures↓ IL-6, interferon-γ induced protein 10 and TNF-α release[133]

Platelet aggregationPomegranate juice or the polyphenol-rich extract from pomegranate fruit⊝ collagen- and arachidonic acid-induced platelet aggregation
↓ collagen- and arachidonic acid-induced calcium mobilization
↓ thromboxane A2 production
↓ H2O2 formation
[136]
Cocoa and dark chocolate↓ ADP-, adrenaline- and, epinephrine-induced GPIIb/IIIa membrane activation
↓ ADP-induced P-selectin membrane expression
↓ PLA2 and COX activity
↓ ROS, 8-iso-PGF2α, and NOX2 activation
[137141]

↑: increase; ↓: decrease; ↔: no change; ⊝: inhibit; ⊕: promote. EVOO: extra virgin olive oil; eNOS: endothelial nitric oxide synthase; NO: nitric oxide; ET-1: endothelin-1; LDL: low-density lipoprotein; ROS: reactive oxygen species; Erk: extracellular-signal-regulated kinase; PDGF: platelet-derived growth factor; VSMCs: vascular smooth muscle cells; MMP-2: matrix metalloproteinase-2; BDNF: brain-derived neurotrophic factor; MIF: migration inhibitory factor; MCP-1: monocyte chemoattractant protein 1; H2O2: hydrogen peroxide; ADP: adenosine diphosphate; GPIIb/IIIa: glycoprotein IIb/IIIa; PLA2: phospholipase A2; COX: cyclooxygenase; 8-iso-PGF2α: 8-isoprostane-prostaglandin F2α; NOX2: NADPH oxidase 2.