Table 1.

Selected phenolics common in red wines and their associated biological activities and health-inducing effects.

Phenol class	Sample biological activities and health protective attributes	References
NON-FLAVONOIDS
Hydroxycinnamic Acids	Prevention of oxidative stress, diabetes, insulin resistance, body weight gain, dyslipidemia, cardiovascular disease, renal disfunction Enhanced potency as an anti-inflammatory agent Improvement of liver function	(58, 59)
Stilbenoids	Cancer treatment and prevention, through mechanisms of apoptosis, inhibition of angiogenesis and proliferation of multiple cancer cell lines Neuroprotection, through reduction of amyloid plaques, cerebral infarct volume, neuronal ROS, and inhibition of cholinesterases Depigmentation, through decreased melanin production and inhibition of tyrosinase activity Protection against cardiomyocyte and cardiac hypertrophy, through activation of AMPK and upregulation of eNOS Blood Pressure Regulation, through lowering of systolic blood pressure at high doses Reduced Platelet Aggregation, through inhibition of COX enzymes Reduction in Obesity, through inhibition of lipogenesis, increased lipolysis, activation of AMPK, SIRT and PGC-1α Management of Diabetes, through enhanced insulin sensitivity, increased AMPK-dependent microbial biogenesis, and increased glucose uptake Defense against Atherosclerosis, through reduction in oxidative stress markers and inhibition of LDL in endothelial cells Protection against UV radiation resulting in reduced DNA damage, skin damage and cancer Protection against Ischemia-reperfusion injury, through increased antioxidant enzymes and reduced oxidative stress	(60–64)
Hydrobenzoic Acids	Antimicrobial properties Amelioration of cardiovascular problems such as hypertension, atherosclerosis, and dyslipidemia Neuroprotection and anti-inflammatory effects providing defense again neurogenerative diseases of Alzheimer's and Parkinson's diseases and amyotrophic lateral sclerosis (ALS)	(65–67)
FLAVONOIDS
Flavonols
Quercetin	Induction of apoptosis, which has been particularly effective in decreasing growth of brain, liver and colon cancers Reduction of coronary artery disease due to increase flow-mediated dilation of major arteries Modulation of inflammation by way of COX and lipoxygenase inhibition Reduction of oxidative damage to lymphocytes and neurovascular structures which inhibits damage to neurons and protects against neurodegenerative disorders Gastroprotective effect by way of inhibition of gastric acid secretion Anti-allergic effect, through inhibition of release of histamine from mast cells	(68–70)
Kaempherol	In combination with Sora, inhibits cell growth inhibition in the S-phase and/or G2/M-phase for hepatocellular carcinomas Induction of cell cycle arrest in proliferating cells Impairment of cancer angiogenesis through inhibition of VEGF secretion in cancer cell lines Inhibition of MMP-3 protein activity in highly-invasive MDA-MB-231 breast cancer, reducing tumor invasion Interruption of cellular pathways (TNF-α, JAK3, IL-8, IL1B) responsible for inflammation	(71–76)
Myricetin	Cytotoxicity in many cancer cell lines including hepatic, skin, pancreatic, and colon cancers Anti-inflammatory effects on periodontitis and rheumatoid arthritis, through various cellular mechanisms Protective effects against Parkinson's Disease and Alzheimer's Disease Vascularprotective effect, through alteration of vascular disease-related genes, including HIRA, HDAC9, HIF1A and RTN3 Management of non-insulin-dependent diabetes, by stimulating the uptake of glucose without functional insulin receptors	(77–79)
Anthocyanins
Delphinidin	Inhibition of EGFR and downstream signaling cascades, most notably in vulvar carcinoma Decrease in cell viability, induction of apoptosis, cleavage of PARP, activation of caspases−3,−8, and−9, increase in Bax with concurrent decrease in Bcl-2 protein, and cell cycle arrest in G2/M phase, in colon cancer Mediated suppression of osteoclast formation, resulting in prevention of bone loss Increase in insulin secretion	(80–83)
Petunidin	Inhibition of breast cancer and liver cancer cell growth, via inhibitory behavior Increase in insulin secretion Inhibition of alpha-glucosidase and lipase in alleviation of diabetes	(83, 84)
Malvidin	Inhibition of various tumor cell lines including promyelocytic/monocytic leukemia cells, colon cancer cells, and gastric adenocarcinoma cells Increase in insulin secretion Antihypertensive activity by inhibition of angiotensin I-converting enzyme and anti-inflammatory effect by blocking NF-κB pathway Counteractive effect on oxidative stress in neuronal cells	(83, 85, 86)
Cyanidin	Inhibition of EGFR and downstream signaling cascades, most notably in vulva carcinoma Induction of cancer cell apoptosis, reduced oxidative damage to DNA, inhibited cell growth and decreased cancer cell proliferation, notably in leukemia, lung, colon, skin and prostate cancer Prevention of Type II Diabetes through enhanced adiponectin and leptin secretion Preventative effect on Type II Diabetes through increased phosphorylation of AMPKα at Thr172 in rat adipose cells	(80, 87)
Peonidin	Chemopreventative and anti-inflammatory effect on inhibition of TPA-induced COX-2 expression, and decreased TPA-induced neoplastic transformation and blocked TPA-induced phosphorylation of extracellular signal–related kinases in breast cancer cells	(88)
Flavanols
(+)-Catechin	Mediation in cardiovascular health via mechanisms of blood pressure reduction, flow-mediated vasodilation, and atherosclerosis attenuation Induction of antioxidative and neuronal anti-inflammatory effects in Alzheimer's Disease	(89, 90)
(–)-Epicatechin	Improvement of endothelium-dependent flow-mediated dilation of the brachial artery important for vascular health Attenuation of atherosclerosis via modulation of NF-κB activity	(91)
Proanthocyanidins (oligomeric/polymeric)	Anti-tumor activity in PC-3 prostate cancer cell lines, through cell cycle arrest, and activation of caspase-3 Inhibition of NF-κB and downstream cascades in human epidermoid carcinoma Reduction in proliferation, increased apoptosis, cell cycle arrest and modulation of key genes beneficially regulates invasion and metastasis for prostate and photocarcinogenesis Protection against oxidative stress and degenerative diseases including cardiovascular dysfunctions, acute and chronic stress, gastrointestinal distress, neurological disorders, pancreatitis, various stages of neoplastic processes, and carcinogenesis including detoxification of carcinogenic metabolites Reduction in hypertension via inhibition of the reactive oxygen species/mitogen-activated protein kinase pathway via restraining the release of ET-1 Inhibition of lipid peroxidation, platelet aggregation, capillary permeability and fragility, and to affect enzyme systems including phospholipase A2, cyclooxygenase, and lipoxygenase	(92–96)