Review Article

Ageing-Associated Oxidative Stress and Inflammation Are Alleviated by Products from Grapes

Table 1

Representative reports on antioxidant and anti-inflammatory effects of grape-derived crude extracts and purified products.

ModelTreatmentOutcomes: inflammationOutcomes: oxidative statusReferences

In vitro:
Glucose and LPS-induced inflammation in HUVEC cellsRed grape polyphenols↓IL-6, IL-8, and NF-κB at protein and mRNA levels
↓PECAM and ICAM-1 levels
↓ROS formation in dose-dependent manner[66]
Primary human chondrocytes challenged with E. coli LPS (arthritis model)Grape extract containing resveratrol, hopeaphenol, and viniferin↓PGE2 production↑scavenging of DPPH radicals[67]
Osteoblast-like cells (MC3T3-Ei), treated with TGF-β to induce VEGF synthesis Resveratrol↓VEGF and VEGF mRNA, but
no effect on p38 or SAPK/JNK, suggesting SIRT1 activation
n.a.[68]
Yeast models of sirtuin activation (c. elegans, D. melanogaster)Resveratrol↑sirtuin (SIRT1) activationn.a.[69, 70]
Human adipose derived stem cells (hASCs)Red grape (muscarine) grape seed oil, in comparison to rice bran and olive oils↓adipogenetic factors (PPARγ and aP2)
↓IL-6 and IL-8 response to LPS
↓proinflammatory gene expression in adipocytes
Shown to be source of γ-tocopherol[71]
High-glucose induced oxidative stress in porcine proximal tubule cells (LLC-PK1)Grape seed polyphenols↓NF-κB pathway↓intracellular ROS[72]
In vivo animal:
Rats exposed to localised bowel irradiationGrape polyphenols OR pure quercetin 3-O-β-glucoside (10 mg/mL, 7.14 mL/kg body mass) by oral gavage for 5 days prior to irradiation↓MPO activity
↓CINC-1 levels
↓SOD activity
No change in glutathione peroxidase (GSHPx) activity
No change in plasma malondialdehyde (MDA) concentration
[73]
Rats subjected to E. coli-induced septic shock75 and 200 mg/kg/day grape seed procyanidin, by ip. injection for 15 days pre-E. coli challenge↓IL-6 gene expression↓NO in liver, spleen, plasma, and RBCs
↓iNos gene expression
↓GSSG: total glutathione ratio
[74]
Rat model of osteoarthritis500 mg/kg body mass of grape extract daily for 28 daysPrevented joint deteriorationn.a.[67]
Rat model of skeletal muscle contusion injuryAcute OR 2-week supplementation, proanthocyanidins↓proinflammatory cytokine signalling (TNF-α; IL-6)
↓neutrophil migration capacity
Earlier macrophage switch from pro- to anti-inflammatory phenotype
↑plasma and skeletal muscle ORAC[50, 75]
Rat model of ageingDrinking water supplemented with 15 g/L grape powder for 3 weeks↓age-associated increase in corticosterone↓plasma 8-isoprostane[76]
Rat model of obesityGrape procyanidin B2↓IL-1β and NLRP3 levels in pancreasn.a.[77]
Middle-aged mice on high-calorie dietDiet supplemented with 0.04% resveratrol↓IGF-1↑AMPK and PGC-1α activity
↑mitochondrial number
[78]
Mouse model of pulmonary fibrosis7-day oral resveratrol (50 mg/kg/day) OR quercetin OR dihydroquercetin (both 10 mg/kg/day)↓neutrophil infiltration into lung tissue
↓inflammatory cells in bronchoalveolar lavage fluid
↓COX-2
↓NF-κBp65 translocation
↓iNOS
↓oxidative lung damage (↓nitrotyrosine and poly-ADP-ribose polymerase levels)
[79]
Rabbit model of acute (E. coli) inflammatory arthritis500 mg/kg body mass of extract acutely prior to E. coli challenge↓PGE2 productionn.a.[67]
In vivo human:
Nondiabetic haemodialysis patientsGrape powder (500 mg polyphenols/day) for 5 weeksPrevented increase in plasma CRP levels↑glutathione peroxidase activity[80]
Humans at risk for metabolic syndrome, aged 30–6516 weeks of 20 g wine grape pomace powder (822 mg polyphenols) per dayn.a.γ- and δ-tocopherol [81]
Hypertensive, T2DM males, aged ≈55–658 mg grape extract daily for 1 year↓alkaline phosphatase
↓TNF-α, IL-1β, IL-6, and CCL3 levels
↑transcriptional repressor LRRFIP-1 in PBMCs
Modulation of expression of group of miRNAs known to regulate inflammatory response
n.a.[82]

ADP, adenosine diphosphate; AMPK, adenosine monophosphate-activated protein kinase; CCL3, chemokine(C-C motif) ligand 3; CINC-1, cytokine-induced neutrophil chemoattractant-1; COX-2, cyclooxygenase-2; DPPH, 2,2-diphenyl-1-picrylhydrazyl; HUVEC, human umbilical vein endothelial cells; iNOS, inducible nitric oxide; ICAM-1, intercellular adhesion molecule-1; IGF-1, insulin growth factor-1; IL, interleukin; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharides; LRRFIP-1, leucine-rich repeat in flii-interacting protein-1; NO, nitric oxide; NF-κB, nuclear factor-kappa beta; ORAC, oxygen radical absorbance capacity; PECAM, platelet endothelial adhesion molecule; PGC-1α, peroxisome proliferator activated receptor gamma coactivator 1-alpha; PGE2, prostaglandin E2;  ROS, reactive oxygen species; SAPK, stress activated protein kinase; VEGF, vascular endothelial growth factor.