Grapes (Vitis vinifera) as a Potential Candidate for the Therapy of the Metabolic Syndrome

Phytotherapy Research

Volumn 30, Issue 4, 2016, Pages 540-556

  Akaberi, Maryam ^a   Hosseinzadeh, Hosein ^b  

^a MASHHAD UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b MASHHAD UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

diabetes mellitus; grape; hyperglycemia; hyperlipidemia; metabolic syndrome; Vitis vinifera

Indexed keywords

ANTHOCYANIN; ASTRAGALIN; CAFFEIC ACID; CATECHIN; COUMARIC ACID; EPICATECHIN GALLATE; FLAVAN 3 OL; FLAVONOID; FLAVONOL DERIVATIVE; GALLIC ACID; GALLIC ACID METHYL ESTER; GLYCYRRHETINIC ACID PHOSPHOLIPID COMPLEX; GRAPE POMACE EXTRACT; GRAPE SEED EXTRACT; GRAPE SKIN EXTRACT; ISOQUERCITRIN; MALVIDIN CHLORIDE; MALVIN; MYRICETIN; PLACEBO; POLYPHENOL; PROANTHOCYANIDIN; PROANTHOCYANIDIN DERIVATIVE; PROCYANIDIN; PROTOCATECHUIC ACID; QUERCETIN; RESVERATROL; RUTOSIDE; TRANS RESVERATROL; UNCLASSIFIED DRUG; UNINDEXED DRUG; ANTIOXIDANT; PLANT MEDICINAL PRODUCT;

ANTIDIABETIC ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; CARDIOVASCULAR DISEASE; CELL PROLIFERATION; DIABETES MELLITUS; DRUG ABSORPTION; DRUG ANALYSIS; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; DRUG STRUCTURE; GRAPE; GRAPE SEED; HUMAN; HYPERGLYCEMIA; HYPERLIPIDEMIA; HYPERTENSION; IN VITRO STUDY; INSULIN RELEASE; INSULIN RESISTANCE; INSULIN SYNTHESIS; LIVER PROTECTION; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PHYTOCHEMISTRY; PLANT SEED; POLYMERIZATION; REVIEW; SIGNAL TRANSDUCTION; STOMACH PROTECTION; ANIMAL; CHEMISTRY; CLINICAL TRIAL (TOPIC); VITIS;

ANIMALS; ANTIOXIDANTS; CLINICAL TRIALS AS TOPIC; GRAPE SEED EXTRACT; HUMANS; METABOLIC SYNDROME X; PHYTOCHEMICALS; POLYPHENOLS; PROANTHOCYANIDINS; SEEDS; VITIS;

EID: 84962644046     PISSN: 0951418X     EISSN: 10991573     Source Type: Journal    
DOI: 10.1002/ptr.5570     Document Type: Review

References (142)

1. (Fao) FaaOOTUN. 2002. FAO Production Yearbook. Food and Agriculture Organization of the United Nations: Rome.
2. Abedini S, Pourghassem Gargari B, Babaei H, Aliasgarzadeh A, Pourabdollahi P,. 2013. Effect of supplementation with grape seed extract (Vitis vinifera) on serum lipid profiles in patient with type 2 diabetes. Iran J Endocrinol Metab 15: 59-66.
3. Adisakwattana S, Moonrat J, Srichairat S, et al., 2010. Lipid-lowering mechanisms of grape seed extract (Vitis vinifera L) and its antihyperlidemic activity. J Med Plant Res 4: 2113-2120.
4. Agarwal C, Sharma Y, Agarwal R,. 2000. Anticarcinogenic effect of a polyphenolic fraction isolated from grape seeds in human prostate carcinoma DU145 cells: modulation of mitogenic signaling and cell-cycle regulators and induction of G1 arrest and apoptosis. Mol Carcinog 28: 129-138.
5. Aguirre L, Fernández-Quintela A, Arias N, Portillo MP,. 2014. Resveratrol: anti-obesity mechanisms of action. Molecules 19: 18632-18655.
6. Ali K, Maltese F, Choi YH, Verpoorte R,. 2010. Metabolic constituents of grapevine and grape-derived products. Phytochem Rev 9: 357-378.
7. Andrade JMO, Paraíso AF, De Oliveira MVM, et al., 2014. Resveratrol attenuates hepatic steatosis in high-fat fed mice by decreasing lipogenesis and inflammation. Nutrition 30: 915-919.
8. Ardévol A, Motilva MJ, Serra A, Blay M, Pinent M,. 2013. Procyanidins target mesenteric adipose tissue in Wistar lean rats and subcutaneous adipose tissue in Zucker obese rat. Food Chem 141: 160-166.
9. Arola-Arnal A, Oms-Oliu G, Crescenti A, et al., 2013. Distribution of grape seed flavanols and their metabolites in pregnant rats and their fetuses. Mol Nutr Food Res 57: 1741-1752.
10. Ayub A, Mackness MI, Arrol S, Mackness B, Patel J, Durrington PN,. 1999. Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 19: 330-335.
11. Baba S, Osakabe N, Natsume M, Muto Y, Takizawa T, Terao J,. 2001. Absorption and urinary excretion of (2)-epicatechin after administration of different levels of cocoa powder or (2)-epicatechin in rats. J Agric Food Chem 49: 6050-6056.
12. Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ,. 1997. Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol 95: 179-189.
13. Bagchi D, Bagchi M, Stohs SJ, et al., 2000. Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 148: 187-197.
14. Bagchi D, Sen CK, Ray SD, et al., 2003. Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat Res 524: 87-97.
15. Bahadoran Z, Mirmiran P, Azizi F,. 2013. Dietary polyphenols as potential nutraceuticals in management of diabetes: a review. J Diabetes Metab Disord 12: 43.
16. Baselga-Escudero L, Blade C, Ribas-Latre A, et al., 2012. Grape seed proanthocyanidins repress the hepatic lipid regulators miR-33 and miR-122 in rats. Mol Nutr Food Res 56: 1636-1646.
17. Baselga-Escudero L, Arola-Arnal A, Pascual-Serrano A, et al., 2013. Chronic administration of proanthocyanidins or docosahexaenoic acid reverses the increase of miR-33a and miR-122 in dyslipidemic obese rats. PLoS One 8.
18. Belcaro G, Ledda A, Hu S, Cesarone MR, Feragalli B, Dugall M,. 2013. Grape seed procyanidins in pre- and mild hypertension: a registry study. J Evid Based Complementary Altern Med 2013: 5.
19. Berrougui H, Grenier G, Loued S, Drouin G, Khalil A,. 2009. A new insight into resveratrol as an atheroprotective compound: inhibition of lipid peroxidation and enhancement of cholesterol efflux. Atherosclerosis 207: 420-427.
20. Berti F, Manfredi B, Mantegazza P, Rossoni G,. 2003. Procyanidins from Vitis vinifera seeds display cardioprotection in an experimental model of ischemia-reperfusion damage. Drugs Exp Clin Res 29: 207-216.
21. Bitsch R, Netzel M, Frank T, Strass G, Bitsch I,. 2004. Bioavailability and biokinetics of anthocyanins from red grape juice and red wine. J Biomed Biotechnol 5: 293-298.
22. Blade C, Baselga-Escudero L, Arola-Arnal A,. 2014. microRNAs as new targets of dietary polyphenols. Curr Pharm Biotechnol 15: 343-351.
23. Boido E, GarcÍa-Marino M, Dellacassa E, Carrau F, Rivas-Gonzalo JC, Escribano-BailÓn MT,. 2011. Characterisation and evolution of grape polyphenol profiles of Vitis vinifera L. cv. Tannat during ripening and vinification. Aust J Grape Wine Res 17: 383-393.
24. Bomser JA, Singletary KW, Wallig MA, Smith ML,. 1999. Inhibition of TPA-induced tumor promotion in CD-1 mouse epidermis by a polyphenolic fraction from grape seeds. Cancer Lett 135: 151-157.
25. Brouillard R, George F, Fougerousse A,. 1997. Polyphenols produced during red wine ageing. Biofactors 6: 403-410.
26. Caimari A, Del Bas JM, Crescenti A, Arola L,. 2013. Low doses of grape seed procyanidins reduce adiposity and improve the plasma lipid profile in hamsters. Int J Obes (Lond) 37: 576-583.
27. Cao G, Muccitelli HU, Sanchez-Moreno C, Prior RL,. 2001. Anthocyanins are absorbed in glycated forms in elderly women: a pharmacokinetic study. Am J Clin Nutr 73: 920-926.
28. Cedó L, Castell-Auví A, Pallarès V, et al., 2012. Pancreatic islet proteome profile in Zucker fatty rats chronically treated with a grape seed procyanidin extract. Food Chem 135: 1948-1956.
29. Cedó L, Castell-Auví A, Pallarès V, Blay M, Ardévol A, Arola L,. 2013. Montserrat Pinent, grape seed procyanidin extract modulates proliferation and apoptosis of pancreatic beta-cells. Food Chem 138: 524-530.
30. Cedó L, Castell-Auví A, Pallarès V, et al., 2014. Gallic acid is an active component for the anticarcinogenic action of grape seed procyanidins in pancreatic cancer cells. Nutr Cancer 66: 88-96.
31. Charradi K, Elkahoui S, Karkouch I, Limam F, Hassine FB, Aouani E,. 2012. Grape seed and skin extract prevents high-fat diet-induced brain lipotoxicity in rat. Neurochem Res 37: 2004-2013.
32. Charradi K, Elkahoui S, Karkouch I, et al., 2013a. Grape seed and skin extract alleviates high-fat diet-induced renal lipotoxicity and prevents copper depletion in rat. Appl Physiol Nutr Metab 38: 259-267.
33. Charradi K, Elkahoui S, Limam F, Aouani E,. 2013b. High-fat diet induced an oxidative stress in white adipose tissue and disturbed plasma transition metals in rat: prevention by grape seed and skin extract. J Physiol Sci 63: 445-455.
34. Charradi K, Mahmoudi M, Elkahoui S, Limam F, Aouani E,. 2013c. Grape seed and skin extract mitigates heart and liver oxidative damage induced by a high-fat diet in the rat: gender dependency. Can J Physiol Pharm 91: 1076-1085.
35. Charradi K, Elkahoui S, Karkouch I, et al., 2014. Protective effect of grape seed and skin extract against high-fat diet-induced liver steatosis and zinc depletion in rat. Digest Dis Sci 59: 1768-1778.
36. Cheng HL, Bryant C, Cook R, O'connor H, Rooney K, Steinbeck K,. 2012. The relationship between obesity and hypoferraemia in adults: a systematic review. Obes Rev 13: 150-161.
37. Cheplick S, Kwon Y, Bhowmik P, Shetty K,. 2010. Phenolic-linked variation in strawberry cultivars for potential dietary management of hyperglycemia and related complications of hypertension. Bioresour Technol 101: 404-413.
38. Cho IJ, Ahn JY, Kim S, Choi MS, Ha TY,. 2008. Resveratrol attenuates the expression of HMG-CoA reductase mRNA in hamsters. Biochem Biophys Res Commun 367: 190-194.
39. Chu KO, et al., 2006. Pharmacokinetic studies of green tea catechins in maternal plasma and fetuses in rats. J Pharm Sci 95: 1372-1381.
40. Clifton PM,. 2004. Effect of grape seed extract and quercetin on cardiovascular and endothelial parameters in high-risk subjects. J Biomed Biotechnol 2004: 272-278.
41. Curin Y, Ritz MF, Andriantsitohaina R,. 2006. Cellular mechanisms of the protective effect of polyphenols on the neurovascular unit in strokes. Cardiovasc Hematol Agents Med Chem 4: 277-288.
42. Dall'Asta M, Calani L, Tedeschi M, et al., 2012. Identification of microbial metabolites derived from in vitro fecal fermentation of different polyphenolic food sources. Nutrition 28: 197-203.
43. De Freitas VP, Glories Y,. 1999. Concentration and compositional changes of procyanidins in grape seeds and skin of white Vitis vinifera varieties. J Sci Food Agr 79: 1601-1606.
44. De Luis DA, Pacheco D, Izaola O, Terroba MC, Cuellar L, Martin T,. 2011. Zinc and copper serum levels of morbidly obese patients before and after biliopancreatic diversion: 4 years of follow-up. J Gastrointest Surg 15: 2178-2181.
45. Déprez S, Brezillon C, Rabot S, et al., 2000. Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular weight phenolic acids. J Nutr 130: 2733-2738.
46. Doshi P, Adsule P, Banerjee K, Oulkar D,. 2013. Phenolic compounds, antioxidant activity and insulinotropic effect of extracts prepared from grape (Vitis vinifera L) byproducts. J Food Sci Technol 1-10.
47. Emiliano AF, De Cavalho LC, Da Silva Cristino Cordeiro V, et al., 2011. Metabolic disorders and oxidative stress programming in offspring of rats fed a high-fat diet during lactation: effects of a vinifera grape skin (ACH09) extract. J Cardiovasc Pharmacol 58: 319-328.
48. Escribano-Bailon T, Gutierrez-Fernandez Y, Rivas-Gonzalo JC, Santos-Buelga C,. 1992. Characterization of procyanidins of Vitis vinifera variety Tinta del Pais grape seeds. J Agr Food Chem 40: 1794-1799.
49. Fernandes I, Azevedo J, Faria A, et al., 2009. Enzymatic hemisynthesis of metabolites and conjugates of anthocyanins. J Agric Food Chem 57: 735-745.
50. Fernández-Iglesias A, Pajuelo D, Quesada H, et al., 2014. Grape seed proanthocyanidin extract improves the hepatic glutathione metabolism in obese Zucker rats. Mol Nutr Food Res 58: 727-737.
51. Ford ES, Giles WH, Dietz WH,. 2002. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. Jama 287: 356-359.
52. Frank T, Netzel M, Strass G, Bitsch R, Bitsch I,. 2003. Bioavailability of anthocyanidin-3-glucosides following consumption of red wine and red grape Juice. Can J Physiol Pharmacol 81: 423-435.
53. Frankel EN, Waterhouse AL, Kinsella JE,. 1993. Inhibition of human LDL oxidation by resveratrol. Lancet: London.
54. Fremont L, Belguendouz L, Delpal S,. 1999. Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids. Life Sci 64: 2511-2521.
55. Galgani J, Ravussin E,. 2008. Energy metabolism, fuel selection and body weight regulation. Int J Obes (Lond) 32: S109-S119.
56. Godse S, Mohan M, Kasture V, Kasture S,. 2010. Effect of myricetin on blood pressure and metabolic alterations in fructose hypertensive rats. Pharm Biol 48: 494-498.
57. Goldberg DM, Hahn SE, Parkes JG,. 1995. Beyond alcohol: beverage consumption and cardiovascular mortality. Clin Chim Acta 237: 155-187.
58. González-Abuín N, Martínez-Micaelo N, Blay M, Ardévol A, Pinent M,. 2014. Grape-seed procyanidins prevent the cafeteria-diet-induced decrease of glucagon-like peptide-1 production. J Agric Food Chem 62: 1066-1072.
59. Graf BL, Raskin I, Cefalu WT, Ribnicky DM,. 2010. Plant-derived therapeutics for the treatment of metabolic syndrome. Curr Opin Investig Drugs 11 (10): 1107-1115.
60. Gris EF, Mattivi F, Ferreira EA, et al., 2011. Stilbenes and tyrosol as target compounds in the assessment of antioxidant and hypolipidemic activity of Vitis vinifera red wines from southern Brazil. J Agric Food Chem 59 (14): 7954-7961.
61. Hidalgo M, Oruna-Concha MJ, Kolida S, et al., 2012. Metabolism of anthocyanins by human gut microflora and their influence on gut bacterial growth. J Agric Food Chem 60: 3882-3890.
62. Hogan S, Zhang L, Li J, Sun S, Canning C, Zhou K,. 2010. Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase. Nutr Metabol 7: 71.
63. Hosseini A, Hosseinzadeh H,. 2015. A review on the effects of Allium sativum (Garlic) in metabolic syndrome. J Endocrinol Invest 1-11.
64. Hosseinzadeh H, Nassiri-Asl M,. 2014. Review of the protective effects of rutin on the metabolic function as an important dietary flavonoid. J Endocrinol Invest 37 (9): 783-788.
65. Jang YS, Jeong JM,. 2010. Antioxidative effect and digestive enzyme inhibition of grape seed extract (GSE). J Korean Soc Food Sci Nutr 39: 783-788.
66. Janle EM, Lila MA, Grannan M, et al., 2010. Pharmacokinetics and tissue distribution of 14C-labeled grape polyphenols in the periphery and the central nervous system following oral administration. J Med Food 13: 926-933.
67. Jeon SM, Lee SA, Choi MS,. 2014. Antiobesity and vasoprotective effects of resveratrol in ApoE-deficient mice. J Med Food 17: 310-316.
68. Joshi VK, Devi MP,. 2009. Resveratrol: importance, role, contents in wine and factors influencing its production. Proc Natl Acad Sci India B 79: 212-226.
69. Kamiyama M, Kishimoto Y, Tani M, Andoh K, Utsunomiya K, Kondo K,. 2009. Inhibition of low-density lipoprotein oxidation by Nagano purple grape (Vitis viniferaxVitis labrusca). J Nutr Sci Vitaminol 55: 471-478.
70. Kantsadi AL, Apostolou A, Theofanous S, et al., 2014. Biochemical and biological assessment of the inhibitory potency of extracts from vinification byproducts of Vitis vinifera extracts against glycogen phosphorylase. Food Chem Toxicol 67: 35-43.
71. Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M,. 2009. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabet Med 26: 526-531.
72. Kaur M, Velmurugan B, Rajamanickam S, Agarwal R, Agarwal C,. 2009. Gallic acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice. Pharm Res 26: 2133-2140.
73. Kim NS, Kang K, Cha MH, et al., 2007. Decreased paraoxonase-1 activity is a risk factor for ischemic stroke in Koreans. Biochem Biophys Res Commun 364: 157-162.
74. Kim H, Bartley GE, Arvik T, et al., 2014. Dietary supplementation of chardonnay grape seed flour reduces plasma cholesterol concentration, hepatic steatosis, and abdominal fat content in high-fat diet-induced obese hamsters. J Agric Food Chem 62: 1919-1925.
75. Kiyici A, Okudan N, Gökbel H, Belviranli M,. 2010. The effect of grape seed extracts on serum paraoxonase activities in streptozotocin-induced diabetic rats. J Med Food 13: 725-728.
76. Kuntz S, Rudloff S, Asseburg H, et al., 2015. Uptake and bioavailability of anthocyanins and phenolic acids from grape/blueberry juice and smoothie in vitro and in vivo. Br J Nutr 113: 1044-1055.
77. Lagouge M, Argmann C, Gerhart-Hines Z, et al., 2006. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 127: 1109-1122.
78. Leifert WR, Abeywardena MY,. 2008. Grape seed and red wine polyphenol extracts inhibit cellular cholesterol uptake, cell proliferation, and 5-lipoxygenase activity. Nutr Res 28: 842-850.
79. Li Y, Ding Y, Zhang Z, Dai X, Jiang Y, Bao L,. 2013. Grape seed proanthocyanidins ameliorate pancreatic beta-cell dysfunction and death in low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats partially by regulating endoplasmic reticulum stress. Nutr Metabol 10:.
80. Liu Y, Pukala TL, Musgrave IF, Williams DM, Dehle FC, Carver JA,. 2013. Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation. Bioorg Med Chem Lett 23: 6336-6340.
81. Manns DC, Mansfield AK,. 2012. A core-shell column approach to a comprehensive high-performance liquid chromatography phenolic analysis of Vitis vinifera L. and interspecific hybrid grape juices, wines, and other matrices following either solid phase extraction or direct injection. J Chromatogr A 17: 111-121.
82. Mansouri E, Khorsandi L, Abedi HA,. 2014. Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats. Iran J Basic Med Sci 17: 461-465.
83. Marques F, de Freitas V, Mateus N,. 2013. Antioxidant and antiproliferative properties of methylated metabolites of anthocyanins. Food Chem 141: 2923-2933.
84. Martin-Gallan P, Carrascosa A, Gussinye M, Dominguez C,. 2003. Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications. Free Radic Biol Med 34: 1563-1574.
85. Méndez-Del Villar M, González-Ortiz M, Martínez-Abundis E, Pérez-Rubio KG, Lizárraga-Valdez R,. 2014. Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord 12: 497-501.
86. Mirmiran P, Bahadoran Z, Azizi F,. 2014. Functional foods-based diet as a novel dietary approach for management of type 2 diabetes and its complications: a review. World J Diabetes 5: 267-281.
87. Miura D, Miura Y, Yagasaki K,. 2003. Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatoma-bearing rats. Life Sci 73: 1393-1400.
88. Miyazawa T, Nakagawa K, Kudo M, Muraishi K, Someya K,. 1999. Direct intestinal absorption of red fruit anthocyanins, cyanidin-3-glucoside and cyanidin- 3, 5-diglucoside, into rats and humans. J Agric Food Chem 47: 1083-1091.
89. Mohamed RH, Karam RA, Abd El-Aziz TA,. 2010. The relationship between paraoxonase1-192 polymorphism and activity with coronary artery disease. Clin Biochem 43: 553-558.
90. Monagas M, Urpi-Sarda M, Sanchez-patan F, Liorach R,. 2010. Insights into the metabolism and microbial biotransformation of dietary flava-3-ols and the bioactivity of their metabolites. Food Funct 1: 233-253.
91. Montagut G, Bladé C, Blay M, et al., 2010. Effects of a grapeseed procyanidin extract (GSPE) on insulin resistance. J Nutr Biochem 21: 961-967.
92. Moreno DA, Ilic N, Poulev A, Brasaemle DL, Fried SK, Raskin I,. 2003. Inhibitory effects of grape seed extract on lipases. Nutrition 19: 876-879.
93. Nakamura Y, Tonogai Y,. 2003. Metabolism of grape seed polyphenol in the rat. J Agric Food Chem 51: 7215-7225.
94. Nassiri-Asl M, Hosseinzadeh H,. 2009. Review of the pharmacological effects of Vitis vinifera (Grape) and its bioactive compounds. Phytother Res 23: 1197-1204.
95. Natella F, Belelli F, Gentili V, Ursini F, Scaccini C,. 2002. Grape seed proanthocyanidins prevent plasma postprandial oxidative stress in humans. J Agric Food Chem 50: 7720-7725.
96. Pfeiffer J, Kuhnel C, Brandt J, et al., 2006. Biosynthesis of flavan 3-ols by leucoanthocyanidin 4-reductases and anthocyanidin reductases in leaves of grape (Vitis vinifera L.), apple (Malus x domestica Borkh.) and other crops. Plant Physiol Biochem 44: 323-334.
97. Poudel PR, Tamura H, Kataoka I, Mochioka R,. 2008. Phenolic compounds and antioxidant activities of skins and seeds of five wild grapes and two hybrids native to Japan. J Food Comp Anal 21: 622-625.
98. Pourghassem-Gargari B, Abedini S, Babaei H, Aliasgarzadeh A, Pourabdollahi P,. 2011. Effect of supplementation with grape seed (Vitis vinifera) extract on antioxidant status and lipid peroxidation in patient with type II diabetes. J Med Plant Res 5: 2029-2034.
99. Prodanov M, Vacas V, Hernández T, Estrella I, Amador B, Winterhalter P,. 2013. Chemical characterisation of Malvar grape seeds (Vitis vinifera L.) by ultrafiltration and RP-HPLC-PAD-MS. J Food Compos Anal 31: 284-292.
100. Ramirez CM, Goedeke L, Fernandez-Hernando C,. 2011. "Micromanaging" metabolic syndrome. Cell Cycle 10: 3249-3252.
101. Razavi BM, Hosseinzadeh H,. 2014. A review of the effects of Nigella sativa L. and its constituent, thymoquinone, in metabolic syndrome. J Endocrinol Invest 37: 1031-1040.
102. Rebello LPG, Lago-Vanzela ES, Barcia MT, et al., 2013. Phenolic composition of the berry parts of hybrid grape cultivar BRS Violeta (BRS Rubea × IAC 1398-21) using HPLC-DAD-ESI-MS/MS. Food Res Int 54: 354-366.
103. Renaud S, De Lorgeril M,. 1992. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339: 1523-1526.
104. Rodríguez Montealegre R, Romero Peces R, Chacón Vozmediano JL, Martínez Gascueña J, García RE,. 2006. Phenolic compounds in skins and seeds of ten grape Vitis vinifera varieties grown in a warm climate. J Food Comp Anal 19: 687-693.
105. Romano B, Pagano E, Montanaro V, Fortunato AL, Milic N, Borrelli F,. 2013. Novel insights into the pharmacology of flavonoids. Phytother Res 27: 1588-1596.
106. Rottiers V, Naar AM,. 2012. MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol 13: 239-250.
107. Sahebkar A,. 2013. Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev 71: 822-835.
108. Saiko P, Szakmary A, Jaeger W, Szekeres T,. 2008. Resveratrol and its analogs: defense against cancer, coronary disease and neurodegenerative maladies or just a fad? Mutat Res 658: 68-94.
109. Sano A, Uchida R, Saito M, et al., 2007. Beneficial effects of grape seed extract on malondialdehyde-modified LDL. J Nutr Sci Vitaminol 53: 174-182.
110. Saucier C, Mirabel M, Daviaud F, Longieras A, Glories Y,. 2001. Rapid fractionation of grape seed proanthocyanidins. J Agric Food Chem 49: 5732-5735.
111. Seo K, Jung S, Park M, Song Y, Choung S,. 2001. Effects of leucocyanidines on activities of metabolizing enzymes and antioxidant enzymes. Biol Pharm Bull 24: 592-593.
112. Serra A, Macia A, Romero MP, Pinol C, Motilva MJ,. 2011. Rapid methods to determine procyanidins, anthocyanins, theobromine and caffeine in rat tissues by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 879: 1519-1528.
113. Serra A, Bladé C, Arola L, Macià A, Motilva MJ,. 2013. Flavanol metabolites distribute in visceral adipose depots after a long-term intake of grape seed proanthocyanidin extract in rats. Br J Nutr 110 (8): 1411-1420.
114. Shanmuganayagam D, Beahm MR, Osman HE, Krueger CG, Reed JD, Folts JD,. 2002. Grape seed and grape skin extracts elicit a greater antiplatelet effect when used in combination than when used individually in dogs and humans. J Nutr 132: 3592-3598.
115. Shanmuganayagam D, Beahm MR, Kuhns MA, Krueger CG, Reed JD, Folts JD,. 2011. Differential effects of grape (Vitis vinifera) skin polyphenolics on human platelet aggregation and low-density lipoprotein oxidation. J Agric Food Chem 60: 5787-5794.
116. Shi J, Yu J, Pohorly JE, Kakuda Y,. 2003. Polyphenolics in grape seeds-biochemistry and functionality. J Med Food 6: 291-299.
117. Siva B, Edirisinghe I, Randolph J, Steinberg F, Kappagoda T,. 2006. Effect of a polyphenoics extracts of grape seeds (GSE) on blood pressure (BP) in patients with the metabolic syndrome (MetS). FASEB J 20: A305.
118. Sivaprakasapillai B, Edirisinghe I, Randolph J, Steinberg F, Kappagoda T,. 2009. Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism 58: 1743-1746.
119. Soares De Moura R, Da Costa GF, Moreira AS, et al., 2012. Vitis vinifera L. grape skin extract activates the insulin-signalling cascade and reduces hyperglycaemia in alloxan-induced diabetic mice. J Pharm Pharmacol 64: 268-276.
120. Song X, Xu H, Feng Y, Li X, Lin M, Cao L,. 2012. Protective effect of grape seed proanthocyanidins against liver ischemic reperfusion injury: Particularly in diet-induced obese mice. Int J Biol Sci 8: 1345-1362.
121. Spencer JP, Schroeter H, Rechner AR, Rice-Evans C,. 2001a. Bioavailability of flavan-3-ols and procyanidins: Gastrointestinal tract influences and their relevance to bioactive forms in ViVo. Antioxid Redox Signaling 3: 1023-1039.
122. Spencer JP, Schroeter H, Shenoy B, Srai SKS, Debnam ES, Rice-Evans C,. 2001b. Epicatechin is the primary bioavailable form of the procyanidin dimers B2 and B5 after transfer across the small intestine. Biochem Biophys Res Commun 285: 588-593.
123. Sri Harsha PS, Gardana C, Simonetti P, Spigno G, Lavelli V,. 2013. Characterization of phenolics, in vitro reducing capacity and anti-glycation activity of red grape skins recovered from winemaking by-products. Bioresour Technol 140: 263-268.
124. Stalmach A, Edwards CA, Wightman JD, Crozier A,. 2012. Gastrointestinal stability and bioavailability of (poly)phenolic compounds following ingestion of Concord grape juice by humans. Mol Nutr Food Res 56: 497-509.
125. Tsai Su C, Singleton VL,. 1969. Identification of three flavan-3-ols from grapes. Phytochemistry 8 (8): 1553-1558.
126. Tsuda T, Horio F, Osawa T,. 1999. Absorption and metabolism of cyanidin-3-O-beta-D-glucoside in rats. FEBS Lett 449: 179-182.
127. Udenigwe CC, Ramprasath VR, Aluko RE, Jones PJ,. 2008. Potential of resveratrol in anticancer and anti-inflammatory therapy. Nutr Rev 66: 445-454.
128. Vigna GB, Costantini F, Aldini G, et al., 2003. Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers. Metabolism 52: 1250-1257.
129. Wang J-N, Hano Y, Nomura T, Chen Y-J,. 2000. Procyanidins from the seeds of Vitis amurensis. Phytochemistry 53: 1097-1102.
130. Wang XY, Ma XH, Li W, et al., 2013. Simultaneous determination of five phenolic components and paeoniflorin in rat plasma by liquid chromatography-tandem mass spectrometry and pharmacokinetic study after oral administration of Cerebralcare granule(w). J Pharm Biomed Anal 86: 82-91.
131. Wang S, Moustaid-Moussa N, Chen L, et al., 2014. Novel insights of dietary polyphenols and obesity. J Nutr Biochem 25: 1-18.
132. Warden BA, Smith LS, Beecher GR, Balentine DA, Clevidence BA,. 2001. Catechins are bioavailable in men and women drinking black tea throughout the day. J Nutr 131: 1731-1737.
133. Wattanakit K, Folsom AR, Selvin E, et al., 2005. Risk factors for peripheral arterial disease incidence in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis 180: 389-397.
134. Wu X, Cao G, Prior RL,. 2002. Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. J Nutr 132: 1865-1871.
135. Xie DY, Dixon RA,. 2005. Proanthocyanidin biosynthesis-still more questions than answers? Phytochemistry 66: 2127-2144.
136. Xie HC, Han HP, Chen Z, He JP,. 2014. A study on the effect of resveratrol on lipid metabolism in hyperlipidemic mice. Afr J Tradit Complement Altern Med 11: 209-212.
137. Yamakoshi J, Kataoka S, Koga T, Ariga T,. 1999. Proanthocyanidin-rich extract from grape seeds attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 142: 139-149.
138. Yamakoshi J, Saito M, Kataoka S, Kikuchi M,. 2002. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem Toxicol 40: 599-607.
139. Yogalakshmi B, Bhuvaneswari S, Sreeja S, Anuradha CV,. 2014. Grape seed proanthocyanidins and metformin act by different mechanisms to promote insulin signaling in rats fed high calorie diet. J Cell Commun Signal 8: 13-22.
140. Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C,. 2003. Interaction between flavonoids and the blood-brain barrier: in vitro studies. J Neurochem 85: 180-192.
141. Zagayko AL, Kravchenko GB, Krasilnikova OA, Ogai YO,. 2013. Grape polyphenols increase the activity of HDL enzymes in old and obese rats. Oxid Med Cell Longev 593761: 14.
142. Zhang XY, Li WG, Wu YJ, et al., 2005. Proanthocyanidin from grape seeds potentiates anti-tumor activity of doxorubicin via immunomodulatory mechanism. Int Immunopharmacol 5: 1247-1257.