Beneficial roles of honey polyphenols against some human degenerative diseases: A review

Alvarez-Suarez JM, Giampieri F, Battino M. Honey as a source of dietary antioxidants: structures, bioavailability and evidence of protective effects against human chronic diseases. Curr Med Chem 2013;20:621–38. Abdel-Moneim WM, Ghafeer HH. The potential protective effect of natural honey against cadmium-induced hepatotoxicity and nephrotoxicity. Mansoura J Forensic Med Clin Toxicol 2007;15:75–92. Yordi EG, Pérez EM, Matos MJ, Villares EU. Antioxidant and pro-oxidant effects of polyphenolic compounds and structure-activity relationship evidence. Nutr Well-Being Health 2012;23–48. Cheynier V. Phenolic compounds: from plants to foods. Phytochem Rev 2012;11:153–77. Graf BA, Milbury PE, Blumberg JB. Flavonols, flavones, flavanones, and human health: epidemiological evidence. J Med Food 2005;8:281–90. Arts IC, Hollman PC. Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr 2005;81:317S–25S. Chow J. Probiotics and prebiotics: a brief overview. J Ren Nutr 2002;12:76–86. Jaganathan SK, Mandal M. Antiproliferative effects of honey and of its polyphenols: a review. Biomed Res Int 20092009:. Dimitrova B, Gevrenova R, Anklam E. Analysis of phenolic acids in honeys of different floral origin by solid-pase extraction and high-performance liquid chromatography. Phytochem Anal 2007;18:24–32. Todd FE, Vansell GH. Pollen grains in nectar and honey. J Econ Entomol 1942;35:728–31. Estevinho L, Pereira AP, Moreira L, Dias LG, Pereira E. Antioxidant and antimicrobial effects of phenolic compounds extracts of Northeast Portugal honey. Food Chem Toxicol 2008;46:3774–9. Nagai T, Inoue R, Kanamori N, Suzuki N, Nagashima T. Characterization of honey from different floral sources. Its functional properties and effects of honey species on storage of meat. Food Chem 2006;97:256–62. Kenjeric D, Mandic ML, Primorac L, Bubalo D, Perl A. Flavonoid profile of Robinia honeys produced in Croatia. Food Chem 2007;102:683–90. Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996;20:933–56. Milner JA. Reducing the risk of cancer. Funct Foods. Springer; 1994 p. 39–70. Duthie GG, Brown KM. Reducing the risk of cardiovascular disease. Funct Foods. Springer; 1994 p. 19–38. Pyrzynska K, Biesaga M. Analysis of phenolic acids and flavonoids in honey. TrAC, Trends Anal Chem 2009;28:893–902. Swartz ME. UPLC™: an introduction and review. J Liq Chromatogr Relat Technol 2005;28:1253–63. Wang S, Zhang J, Chen X, Hu Z. Study of the electrophoretic behaviour of flavonoids. Chromatographia 2004;59:507–11. Harborne JB, Williams CA. Advances in flavonoid research since 1992. Phytochemistry 2000;55:481–504. Bravo L. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998;56:317–33. Cheynier V. Polyphenols in foods are more complex than often thought. Am J Clin Nutr 2005;81:223S–9S. Tomás-Barberán FA, Martos I, Ferreres F, Radovic BS, Anklam E. HPLC flavonoid profiles as markers for the botanical origin of European unifloral honeys. J Sci Food Agric 2001;81:485–96. Al-Mamary M, Al-Meeri A, Al-Habori M. Antioxidant activities and total phenolics of different types of honey. Nutr Res 2002;22:1041–7. Organization WH. Prevention of cardiovascular disease. WHO; 2007. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999;340:115–26. Kelly BB, Fuster V. Promoting cardiovascular health in the developing world: a critical challenge to achieve global health. NAP; 2010. Finks SW, Airee A, Chow SL, Macaulay TE, Moranville MP, Rogers KC, et al. Key articles of dietary interventions that influence cardiovascular mortality. Pharmacotherapy 2012;32:e54–87. Ulbricht T, Southgate D. Coronary heart disease: seven dietary factors. Lancet 1991;338:985–92. Rein D, Lotito S, Holt RR, Keen CL, Schmitz HH, Fraga CG. Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma oxidation status. J Nutr 2000;130:2109S–14S. Stein JH, Keevil JG, Wiebe DA, Aeschlimann S, Folts JD. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation 1999;100:1050–5. Rein D, Paglieroni TG, Wun T, Pearson DA, Schmitz HH, Gosselin R, et al. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000;72:30–5. Desch S, Schmidt J, Kobler D, Sonnabend M, Eitel I, Sareban M, et al. Effect of cocoa products on blood pressure: systematic review and meta-analysis. Am J Hypertens 2010;23:97–103. Erlund I, Koli R, Alfthan G, Marniemi J, Puukka P, Mustonen P, et al. Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr 2008;87:323–31. Taubert D, Roesen R, Lehmann C, Jung N, Schömig E. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA 2007;298:49–60. Heiss C, Dejam A, Kleinbongard P, Schewe T, Sies H, Kelm M. Vascular effects of cocoa rich in flavan-3-ols. JAMA 2003;290:1030–1. Heiss C, Kleinbongard P, Dejam A, Perré S, Schroeter H, Sies H, et al. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J Am Coll Cardiol 2005;46:1276–83. Schramm DD, Karim M, Schrader HR, Holt RR, Kirkpatrick NJ, Polagruto JA, et al. Food effects on the absorption and pharmacokinetics of cocoa flavanols. Life Sci 2003;73:857–69. Mao T, Van de Water J, Keen CL, Schmitz H, Gershwin ME. Modulation of TNF-α secretion in peripheral blood mononuclear cells by cocoa flavanols and procyanidins. J Immunol Res 2002;9:135–41. Solayman M, Ali Y, Alam F, Islam A, Alam N, Ibrahim Khalil M, et al. Polyphenols: potential future arsenals in the treatment of diabetes. Curr Pharm Des 2016;22:549–65. Urquiaga I, Leighton F. Plant polyphenol antioxidants and oxidative stress. Biol Res 2000;33:55–64. Benavente-Garcia O, Castillo J. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food Chem 2008;56:6185–205. Wan Y, Vinson JA, Etherton TD, Proch J, Lazarus SA, Kris-Etherton PM. Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. Am J Clin Nutr 2001;74:596–602. Mathur S, Devaraj S, Grundy SM, Jialal I. Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans. J Nutr 2002;132:3663–7. Larocca LM, Teofili L, Sica S, Piantelli M, Maggiano N, Leone G, et al. Quercetin inhibits the growth of leukemic progenitors and induces the expression of transforming growth factor-beta 1 in these cells. Blood 1995;85:3654–61. Hanasaki Y, Ogawa S, Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med 1994;16:845–50. Mahesh T, Menon VP. Quercetin allievates oxidative stress in streptozotocin-induced diabetic rats. Phytother Res 2004;18:123–7. Molina MF, Sanchez-Reus I, Iglesias I, Benedi J. Quercetin, a flavonoid antioxidant, prevents and protects against ethanol-induced oxidative stress in mouse liver. Biol Pharm Bull 2003;26:1398–402. Lafay S, Gueux E, Rayssiguier Y, Mazur A, Rémésy C, Scalbert A. Caffeic acid inhibits oxidative stress and reduces hypercholesterolemia induced by iron overload in rats. Int J Vitam Nutr Res 2005;75:119–25. Ozguner F, Altinbas A, Ozaydin M, Dogan A, Vural H, Kisioglu AN, et al. Mobile phone-induced myocardial oxidative stress: protection by a novel antioxidant agent caffeic acid phenethyl ester. Toxicol Ind Health 2005;21:223–30. Ishige K, Schubert D, Sagara Y. Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radic Biol Med 2001;30:433–46. Samhan-Arias AK, Martı’n-Romero FJ, Gutiérrez-Merino C. Kaempferol blocks oxidative stress in cerebellar granule cells and reveals a key role for reactive oxygen species production at the plasma membrane in the commitment to apoptosis. Free Radic Biol Med 2004;37:48–61. Jin B-h, Qian L-b, Chen S, Li J, Wang H-p, Bruce IC, et al. Apigenin protects endothelium-dependent relaxation of rat aorta against oxidative stress. Eur J Pharmacol 2009;616:200–5. Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002;8:1227–35. O’malley T, Langhorne P, Elton R, Stewart C. Platelet size in stroke patients. Stroke 1995;26:995–9. Angiolillo DJ, Bernardo E, Sabaté M, Jimenez-Quevedo P, Costa MA, Palazuelos J, et al. Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 2007;50:1541–7. Guerrero J, Lozano M, Castillo J, Benavente-garcía O, Vicente V, Rivera J. Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor. J Thromb Haemost 2005;3:369–76. Hubbard G, Wolffram S, Lovegrove J, Gibbins J. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost 2004;2:2138–45. Egert S, Bosy-Westphal A, Seiberl J, Kürbitz C, Settler U, Plachta-Danielzik S, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr 2009;102:1065–74. Kostyuk VA, Potapovich AI, Suhan TO, de Luca C, Korkina LG. Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation. Eur J Pharmacol 2011;658:248–56. Al-Awwadi NA, Araiz C, Bornet A, Delbosc S, Cristol J-P, Linck N, et al. Extracts enriched in different polyphenolic families normalize increased cardiac NADPH oxidase expression while having differential effects on insulin resistance, hypertension, and cardiac hypertrophy in high-fructose-fed rats. J Agric Food Chem 2005;53:151–7. Romero M, Jiménez R, Sánchez M, López-Sepúlveda R, Zarzuelo MJ, O’Valle F, et al. Quercetin inhibits vascular superoxide production induced by endothelin-1: role of NADPH oxidase, uncoupled eNOS and PKC. Atherosclerosis 2009;202:58–67. Sánchez M, Galisteo M, Vera R, Villar IC, Zarzuelo A, Tamargo J, et al. Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J Hypertens 2006;24:75–84. Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco 2001;56:683–7. Lee J-H, Zhou HY, Cho SY, Kim YS, Lee YS, Jeong CS. Anti-inflammatory mechanisms of apigenin: inhibition of cyclooxygenase-2 expression, adhesion of monocytes to human umbilical vein endothelial cells, and expression of cellular adhesion molecules. Arch Pharm Res 2007;30:1318–27. Kong L, Luo C, Li X, Zhou Y, He H. The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits. Lipids Health Dis 2013;12:115. Patel D, Kumar R, Laloo D, Hemalatha S. Diabetes mellitus: an overview on its pharmacological aspects and reported medicinal plants having antidiabetic activity. Asian Pac J Trop Biomed 2012;2:411–20. Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diab Care 1989;12:553–64. Marles RJ, Farnsworth NR. Antidiabetic plants and their active constituents. Phytomedicine 1995;2:137–89. Gray AM, Flatt PR. Nature’s own pharmacy: the diabetes perspective. Proc Nutr Soc 1997;56:507–17. Mcdougall GJ, Stewart D. The inhibitory effects of berry polyphenols on digestive enzymes. Biofactors 2005;23:189–95. McDougall GJ, Shpiro F, Dobson P, Smith P, Blake A, Stewart D. Different polyphenolic components of soft fruits inhibit α-amylase and α-glucosidase. J Agric Food Chem 2005;53:2760–6. Jung UJ, Lee M-K, Jeong K-S, Choi M-S. The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice. J Nutr 2004;134:2499–503. Rouse M, Younès A, Egan JM. Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity. J Endocrinol 2014;223:107–17. Sabu M, Smitha K, Kuttan R. Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes. J Ethnopharmacol 2002;83:109–16. Eid HM, Martineau LC, Saleem A, Muhammad A, Vallerand D, Benhaddou-Andaloussi A, et al. Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea. Mol Nutr Food Res 2010;54:991–1003. Hii C, Howell S. Effects of flavonoids on insulin secretion and 45Ca2+ handling in rat islets of Langerhans. J Endocrinol 1985;107:1–8. Cao H, Polansky MM, Anderson RA. Cinnamon extract and polyphenols affect the expression of tristetraprolin, insulin receptor, and glucose transporter 4 in mouse 3T3-L1 adipocytes. Arch Biochem Biophys 2007;459:214–22. Varma SD, Kinoshita JH. Inhibition of lens aldose reductase by flavonoids—their possible role in the prevention of diabetic cataracts. Biochem Pharmacol 1976;25:2505–13. Tundis R, Loizzo M, Menichini F. Natural products as α-amylase and α-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: an update. Mini Rev Med Chem 2010;10:315–31. Hussain S, Mahwi T, Aziz T. Quercetin dampens postprandial hyperglycemia in type 2 diabetic patients challenged with carbohydrates load. Int J Diab Dev Res 2012;1:32–5. Tadera K, Minami Y, Takamatsu K, Matsuoka T. Inhibition of α-glucosidase and α-amylase by flavonoids. J Nutr Sci Vitaminol (Tokyo) 2006;52:149–53. Jong-Sang K, Chong-Suk K, Son KH. Inhibition of alpha-glucosidase and amylase by luteolin, a flavonoid. Biosci Biotechnol Biochem 2000;64:2458–61. Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol C: Toxicol Pharmacol 2003;135:357–64. Adewole SO, Caxton-Martins EA, Ojewole JA. Protective effect of quercetin on the morphology of pancreatic β-cells of streptozotocin-treated diabetic rats. AJTCAM 2006;4:64–74. Esmaeili MA, Sadeghi H. Pancreatic B-cell protective effect of rutin and apigenin isolated from Teucrium polium. Pharmacologyonline 2009;2:341–53. Alkhalidy H, Moore W, Zhang Y, McMillan R, Wang A, Ali M, et al. Small molecule kaempferol promotes insulin sensitivity and preserved pancreatic β-cell mass in middle-aged obese diabetic mice. J Diab Res 20152015:. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010;107:1058–70. Coskun O, Kanter M, Korkmaz A, Oter S. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Pharmacol Res 2005;51:117–23. Gordon MH, Roedig-Penman A. Antioxidant activity of quercetin and myricetin in liposomes. Chem Phys Lipids 1998;97:79–85. Panickar K, Polansky M, Anderson R. Myricetin and quercetin attenuate ischemic injury in glial cultures by different mechanisms. Neurosci Lett Suppl 2009 [access on 10 September 2016]. Available online: http://ppmq.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=240566. Wang G, Li W, Lu X, Bao P, Zhao X. Luteolin ameliorates cardiac failure in type I diabetic cardiomyopathy. J Diab Complicat 2012;26:259–65. Lee C-C, Hsu W-H, Shen S-R, Cheng Y-H, Wu S-C. Fagopyrum tataricum (buckwheat) improved high-glucose-induced insulin resistance in mouse hepatocytes and diabetes in fructose-rich diet-induced mice. Exp Diab Res 20122012:. Prabhakar PK, Doble M. Synergistic effect of phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes. Phytomedicine 2009;16:1119–26. Kamalakkannan N, Prince PSM. Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats. Basic Clin Pharmacol Toxicol 2006;98:97–103. Cazarolli LH, Folador P, Moresco HH, Brighente IMC, Pizzolatti MG, Silva FRMB. Mechanism of action of the stimulatory effect of apigenin-6-C-(2″-O-α-L-rhamnopyranosyl)-β-L-fucopyranoside on 14 C-glucose uptake. Chem Biol Interact 2009;179:407–12. Youl E, Bardy G, Magous R, Cros G, Sejalon F, Virsolvy A, et al. Quercetin potentiates insulin secretion and protects INS-1 pancreatic β-cells against oxidative damage via the ERK1/2 pathway. Br J Pharmacol 2010;161:799–814. Zarzuelo A, Jimenez I, Gamez M, Utrilla P, Fernadez I, Torres M, et al. Effects of luteolin 5-O-β-rutinoside in streptozotocin-induced diabetic rats. Life Sci 1996;58:2311–6. Ding L, Jin D, Chen X. Luteolin enhances insulin sensitivity via activation of PPARg transcriptional activity in adipocytes. J Nutr Biochem 2010;21:941–7. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57–70. Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 2008;25:2097–116. Block G, Patterson B, Subar A. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer 1992;18:1–29. Swellam T, Miyanaga N, Onozawa M, Hattori K, Kawai K, Shimazui T, et al. Antineoplastic activity of honey in an experimental bladder cancer implantation model: in vivo and in vitro studies. Int J Urol 2003;10:213–9. Brglez Mojzer E, Knez Hrnčič M, škerget M, Knez Ž, Bren U. Polyphenols: extraction methods, antioxidative action, bioavailability and anticarcinogenic effects. Molecules 2016;21:901. Kuntz S, Wenzel U, Daniel H. Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Eur J Nutr 1999;38:133–42. Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H. Targeting multiple signaling pathways by green tea polyphenol (−)-epigallocatechin-3-gallate. Cancer Res 2006;66:2500–5. Corona G, Deiana M, Incani A, Vauzour D, Dessì MA, Spencer JP. Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects. Biochem Biophys Res Commun 2007;362:606–11. Ishikawa Y, Kitamura M. Bioflavonoid quercetin inhibits mitosis and apoptosis of glomerular cells in vitro and in vivo. Biochem Biophys Res Commun 2000;279:629–34. Mantena SK, Baliga MS, Katiyar SK. Grape seed proanthocyanidins induce apoptosis and inhibit metastasis of highly metastatic breast carcinoma cells. Carcinogenesis 2006;27:1682–91. Adams LS, Chen S. Phytochemicals for breast cancer prevention by targeting aromatase. Front Biosci (Landmark Ed) 2008;14:3846–63. Katiyar SK, Afaq F, Perez A, Mukhtar H. Green tea polyphenol (−)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress. Carcinogenesis 2001;22:287–94. Feng Q, Torii Y, Uchida K, Nakamura Y, Hara Y, Osawa T. Black tea polyphenols, theaflavins, prevent cellular DNA damage by inhibiting oxidative stress and suppressing cytochrome P450 1A1 in cell cultures. J Agric Food Chem 2002;50:213–20. Vijayababu M, Kanagaraj P, Arunkumar A, Ilangovan R, Aruldhas M, Arunakaran J. Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression. J Cancer Res Clin Oncol 2005;131:765–71. Ujiki MB, Ding X-Z, Salabat MR, Bentrem DJ, Golkar L, Milam B, et al. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest. Mol Cancer 2006;5:76. Weng M-S, Ho Y-S, Lin J-K. Chrysin induces G1 phase cell cycle arrest in C6 glioma cells through inducing p21 Waf1/Cip1 expression: involvement of p38 mitogen-activated protein kinase. Biochem Pharmacol 2005;69:1815–27. Samarghandian S, Afshari JT, Davoodi S. Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line pc-3. Clinics 2011;66:1073–9. Kim J-H, Jin Y-R, Park B-S, Kim T-J, Kim S-Y, Lim Y, et al. Luteolin prevents PDGF-BB-induced proliferation of vascular smooth muscle cells by inhibition of PDGF β-receptor phosphorylation. Biochem Pharmacol 2005;69:1715–21. Park CH, Chang JY, Hahm ER, Park S, Kim H-K, Yang CH. Quercetin, a potent inhibitor against β-catenin/Tcf signaling in SW480 colon cancer cells. Biochem Biophys Res Commun 2005;328:227–34. Gulati N, Laudet B, Zohrabian Vm, Murali R, Jhanwar-Uniyal M. The antiproliferative effect of quercetin in cancer cells is mediated via inhibition of the PI3K-Akt/PKB pathway. Anticancer Res 2006;26:1177–81. Barzilai A, Melamed E. Molecular mechanisms of selective dopaminergic neuronal death in Parkinson’s disease. Trends Mol Med 2003;9:126–32. Jellinger K. Cell death mechanisms in neurodegeneration. J Cell Mol Med 2001;5:1–17. Spires TL, Hannan AJ. Nature, nurture and neurology: gene-environment interactions in neurodegenerative disease. FEBS J 2005;272:2347–61. Cirmi S, Ferlazzo N, Lombardo GE, Ventura-Spagnolo E, Gangemi S, Calapai G, et al. Neurodegenerative diseases might citrus flavonoids play a protective role? Molecules 2016;21:1312. Inanami O, Watanabe Y, Syuto B, Nakano M, Tsuji M, Kuwabara M. Oral administration of (−) catechin protects against ischemia-reperfusion-induced neuronal death in the gerbil. Free Radic Res 1998;29:359–65. Youdim KA, Joseph JA. A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radic Biol Med 2001;30:583–94. Luo Y, Smith JV, Paramasivam V, Burdick A, Curry KJ, Buford JP, et al. Inhibition of amyloid-β aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Natl Acad Sci U S A 2002;99:12197–202. Bastianetto S, Zheng WH, Quirion R. The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity. J Neurochem 2000;74:2268–77. Vauzour D, Vafeiadou K, Rice-Evans C, Williams RJ, Spencer JP. Activation of pro-survival Akt and ERK1/2 signalling pathways underlie the anti-apoptotic effects of flavanones in cortical neurons. J Neurochem 2007;103:1355–67. Jang S, Dilger RN, Johnson RW. Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice. J Nutr 2010;140:1892–8. Xu B, Li X-X, He G-R, Hu J-J, Mu X, Tian S, et al. Luteolin promotes long-term potentiation and improves cognitive functions in chronic cerebral hypoperfused rats. Eur J Pharmacol 2010;627:99–105. Hu P, Wang M, Chen W-H, Liu J, Chen L, Yin S-T, et al. Quercetin relieves chronic lead exposure-induced impairment of synaptic plasticity in rat dentate gyrus in vivo. Naunyn Schmiedebergs Arch Pharmacol 2008;378:43–51. Kumar A, Sehgal N, Kumar P, Padi S, Naidu P. Protective effect of quercetin against ICV colchicine-induced cognitive dysfunctions and oxidative damage in rats. Phytother Res 2008;22:1563–9. Li S, Pu X-P. Neuroprotective effect of kaempferol against a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced mouse model of Parkinson’s disease. Biol Pharm Bull 2011;34:1291–6. Koh P-O. Ferulic acid prevents the cerebral ischemic injury-induced decrease of Akt and Bad phosphorylation. Neurosci Lett 2012;507:156–60. Cheng C-Y, Su S-Y, Tang N-Y, Ho T-Y, Chiang S-Y, Hsieh C-L. Ferulic acid provides neuroprotection against oxidative stress-related apoptosis after cerebral ischemia/reperfusion injury by inhibiting ICAM-1 mRNA expression in rats. Brain Res 2008;1209:136–50. Li Y, Shi W, Li Y, Zhou Y, Hu X, Song C, et al. Neuroprotective effects of chlorogenic acid against apoptosis of PC12 cells induced by methylmercury. Environ Toxicol Pharmacol 2008;26:13–21. Kwon S-H, Lee H-K, Kim J-A, Hong S-I, Kim H-C, Jo T-H, et al. Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. Eur J Pharmacol 2010;649:210–7.