Table 4.

The cardioprotective effects, antioxidant, and anti-inflammatory actions of polyphenols and grape pomace on different cardiac experimental injuries.

In Vitro Studies
Materials	Models	Antioxidant and Anti-Inflammatory Effects	References
Resveratrol—100 μmol/L	Neonatal cardiac cells under ischemia/reperfusion exposure	-increased Bcl-2 expression -increased SOD levels -increased cell viability -increased the activity of Ca2+ -ATPase and Na+-K+ -ATPase -reduced the activity of caspase-3 and LDH -reduced apoptotic rate -reduced Bax expression -reduced MDA levels	[79]
Resveratrol—1 mL/2.5 mg/kg food	H2O2 exposed cardiomyocytes sampled from Sprague Dawley rats	-averted the activity reduction of CAT and SOD	[80]
Resveratrol—3 μM	Human cardiomyocytes’ azidothymidine-induced cardiotoxicity	-decreased the activity of caspase-3, caspase-7 -decreased mitochondrial ROS generation -decreased cardiomyocytes apoptosis	[83]
Resveratrol—3 μM	Neonatal human cardiomyocytes in a medium with endotoxin lipopolysaccharide	-decreased the mitochondrial production of ROS	[84]
Grape pomace from Vitis vinifera L. cv. Barbera, Carignan, Cabernet Sauvignon, Grenache, Merlot, Petit Verdot, Syrah, Tempranillo and Zinfandel from Baja California, Mexico/methanol extract	Human platelets from 6 healthy persons	-GP from Petit Verdot possessed significant anti-platelets aggregation induced by ADP and TRAP-6	[86]
Grape pomace from Vitis vinifera from Hamburg, Germany	Blood samples	-inhibited the ADP-induced platelets aggregation -anticoagulant effect–prolonged activated partial -thromboplastin time (APPT) and prothrombin time (PT)	[87]
12 GP from white (Italia, Baresana, Beogradska, Autumn Seedless), red (Crimson Seedless, Red Globe, Apulia Rose, Supernova) and black (Autumn Royal, Michele Palieri, Summer Royal) from Turi, Italy	Blood samples from healthy donors Mononuclear cells isolated from the blood samples	-on blood: inhibited the LPS-induced TF activity, where RGP had the highest inhibition rate, followed by WGP and BGP -on mononuclear cells: inhibited the PLS-induced TF activity expression, where Supernova (red) had the highest inhibition rate	[88]
Resveratrol—25 μM	Neonatal rat cardiac cells in a medium with fractalkine	-conserved cardiac cell viability -augmented cardiac cells autophagy -decreased levels of MMP-9, ANP, ICAM-1, TGF-β, FKN, procollagens I and III	[91]
In vivo studies
Red grape pomace—10% concentration	60 rats with atherogenic diet-induced ischemic heart disease	-decreased levels of IL-10 and TNF-α -decreased the number and dimension of atherosclerotic lesions -increased levels of HDL cholesterol -restored the ejection fraction in the left ventricle	[78]
Grape skin and seed extract from Vitis vinifera cultivated in northern Tunisia—4 g/kg	24 Wistar male rats with cardiac injury and oxidative stress induced by arsenic	-increased SOD, GPx and CAT activities -reduced the levels of free iron, ionizable calcium and H2O2	[81]
Grape seed proanthocyanidins—100 mg/kg, twice a day	Ischemic-induced left ventricle by a 0.09% NaCl–4oC solution from 32 Rattus Norvegicus rats	-reduced ischemia-related MDA -increased SOD, GPx and CAT levels	[82]
Resveratrol—10 mg/kg IP injection	C57BL/6 mice with endotoxin-induced cardiomyopathy	-reduced the increase of CK and LDH levels	[84]
Resveratrol—10 mg/kg/day	L-NAME-induced malignant hypertension mice	-decreased superoxide anion radical, TBARs, MPO, thiol groups -decreased the damage score of cardiomyocytes -decreased expression of TGF-β -increased NO2 -averted reduction of antioxidant enzymes: SOD, GRx, GPx, CAT	[85]
Resveratrol—20 mg/kg IP injection for 42 days * IP—intraperitoneal injection	C57BL/6 mice with myocardial infarction surgical-induced	-increased the function of the left ventricle -increased survival rate -reduced the infarction size of the left ventricle	[91]
Resveratrol—2.5 mg/kg for 15 days	Rats under ischemic/reperfusion exposure	-decreased infarction size -reduced ROS and GSH levels -increased aortic flow -increased the development of left ventricular pressure post-ischemia	[92]
Methanolic extract from Vitis vinifera seed—125/250 mg/kg	Isoproterenol-induced infarction and streptozotocin-induced diabetes in Wistar mice	-decreased LPO levels -decreased expression of RAGE protein -decreased TNF-α, IL-1β, IL-6, NF- κβ and Iκκβ levels -increased CAT, GPx and SOD levels -increased the activity of Ca2+ -ATPase and Na+-K+ -ATPase	[93]
Resveratrol—30/100 mg/kg for 7 days	Heart sampled from ApoE-KO rats	-decreased levels of ROS and superoxide -decreased expression of NOX2 and NOX 4, with no effect on NOX1 -increased expression of SOD (SOD1, SOD2 and SOD3), catalase and GSH-Px	[94]

Abbreviations: ROS—Reactive oxygen species; ICAM-1—Intercellular adhesion molecule 1; MMP-9—Matrix metallopeptidase 9; FKN—Fractalkine; SOD—Superoxide dismutase; LDH—Lactate dehydrogenase; MDA—Malondialdehyde; CAT—catalase; ANP—Atrial natriuretic peptide; TGF-β—Transforming growth factor beta; GPx/GSH-Px—Glutathione peroxidase; LPO—Lipid peroxidation; IL-10—Interleukin-10; TNF-α—Tumor necrosis factor alpha; HDL—High-density lipoprotein; NF-kb—Nuclear factor kappa-light-chain-enhancer of activated B cells; Ikkb—Inhibitor of nuclear factor kappa-B kinase subunit beta; IL-1b—interleukin-1b; IL-6, interleukin-6; TBARs—Thiobarbituric acid reactive substances; MPO—Myeloperoxidase; GSH—Glutathione; GRx—Glutathione reductase; NOX – nitrate oxide.