Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

Author(s): Ambreen Fatima, Yasir Hasan Siddique*.

Journal Name: CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)

Volume 18 , Issue 8 , 2019

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Graphical Abstract:


Abstract:

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

Keywords: Flavanoids, tangeritin, neurodegeneration, biosynthetic pathway, polyphenols, flavones.

[1]
Dwivedi S, Malik C, Chhokar V. Molecular structure, biological functions, and metabolic regulation of flavonoids. In: Recent Advancements and Developments. Singapore 2017; Springer; pp. 171- 88.
[2]
Foti MC, Amorati R. ROS and phenolic compounds reactive oxygen species in biology and human health. Boca Raton: CRC Press 2016; pp. 49-53.
[3]
Dixon RA, Dey PM, Lamb CJ. Phytoalexins, enzymology and molecular biology. Adv Enzymol Relat Areas Mol Biol 1983; 55: 1-136.
[PMID: 6353887]
[4]
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: A review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001; 74(4): 418-25.
[http://dx.doi.org/10.1093/ajcn/74.4.418] [PMID: 11566638]
[5]
Formica JV, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol 1995; 33(12): 1061-80.
[http://dx.doi.org/10.1016/0278-6915(95)00077-1] [PMID: 8847003]
[6]
Gurib-Fakim A. medicinal plants. Traditions of yesterday and drugs of tomorrow. Mol Aspects Med 2006; 27(1): 1-93.
[http://dx.doi.org/10.1016/j.mam.2005.07.008] [PMID: 16105678]
[7]
Beecher GR. Overview of dietary flavonoids: Nomenclature, occurrence and intake. J Nutr 2003; 133(10): 3248S-54S.
[http://dx.doi.org/10.1093/jn/133.10.3248S] [PMID: 14519822]
[8]
Middleton E. Effect of plant flavonoids on immune and inflammatory cell function Flavonoids in the Living System. Boston: Springer 1998; pp. 175-82.
[http://dx.doi.org/10.1007/978-1-4615-5335-913]
[9]
Lin CH, Chang CY, Lee KR, Lin HJ, Chen TH, Wan L. Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway. BMC Cancer 2015; 15: 958.
[http://dx.doi.org/10.1186/s12885-015-1965-7] [PMID: 26675309]
[10]
Pietta P, Gardana C, Pietta A. Flavonoids in herbs. Oxidative Stress Dis 2003; 9: 43-70.
[11]
Fraga CG, Actis-Goretta L, Ottaviani JI, et al. Regular consumption of a flavanol-rich chocolate can improve oxidant stress in young soccer players. Clin Dev Immunol 2005; 12(1): 11-7.
[http://dx.doi.org/10.1080/10446670410001722159] [PMID: 15712594]
[12]
Selmi C, Mao TK, Keen CL, Schmitz HH, Eric Gershwin M. The anti-inflammatory properties of cocoa flavanols. J Cardiovasc Pharmacol 2006; 47(Suppl. 2): S163-71.
[http://dx.doi.org/10.1097/00005344-200606001-00010] [PMID: 16794453]
[13]
Fisher ND, Hollenberg NK. Flavanols for cardiovascular health: The science behind the sweetness. J Hypertens 2005; 23(8): 1453-9.
[http://dx.doi.org/10.1097/01.hjh.0000174605.34027.9d] [PMID: 16003167]
[14]
Ren MQ, Kuhn G, Wegner J, Chen J. Isoflavones: Substances with multi-biological and clinical properties. Eur J Nutr 2001; 40(4): 135-46.
[http://dx.doi.org/10.1007/PL00007388] [PMID: 11905954]
[15]
Weng CJ, Yen GC. Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Cancer Metastasis Rev 2012; 31(1-2): 323-51.
[http://dx.doi.org/10.1007/s10555-012-9347-y] [PMID: 22314287]
[16]
Huang B, Guo J, Yi B, Yu X, Sun L, Chen W. Heterologous production of secondary metabolites as pharmaceuticals in Saccharomyces cerevisiae. Biotechnol Lett 2008; 30(7): 1121-37.
[http://dx.doi.org/10.1007/s10529-008-9663-z] [PMID: 18512022]
[17]
Kim MJ, Kim BG, Ahn JH. Biosynthesis of bioactive O-methylated flavonoids in Escherichia coli. Appl Microbiol Biotechnol 2013; 97(16): 7195-204.
[http://dx.doi.org/10.1007/s00253-013-5020-9] [PMID: 23771780]
[18]
Winkel BS. Metabolic channeling in plants. Annu Rev Plant Biol 2004; 55: 85-107.
[http://dx.doi.org/10.1146/annurev.arplant.55.031903.141714] [PMID: 15725058]
[19]
Li H, Dong Y, Yang J, et al. De novo transcriptome of safflower and the identification of putative genes for oleosin and the biosynthesis of flavonoids. PLoS One 2012; 7(2)e30987
[http://dx.doi.org/10.1371/journal.pone.0030987] [PMID: 22363528]
[20]
Andersen ØM, Jordheim M. Flavonids: Chemistry of flavonoid-based colors in plants.Comprehensive Natural Products II Chemistry and Biology. Boca Raton: CRC Press 2010; pp. 547-614.
[21]
Besseau S, Hoffmann L, Geoffroy P, Lapierre C, Pollet B, Legrand M. Flavonoid accumulation in Arabidopsis repressed in lignin synthesis affects Auxin transport and plant growth. Plant Cell 2007; 19(1): 148-62.
[http://dx.doi.org/10.1105/tpc.106.044495] [PMID: 17237352]
[22]
Braidot E, Zancani M, Petrussa E, et al. Transport and accumulation of flavonoids in grapevine (Vitis vinifera L.). Plant Signal Behav 2008; 3(9): 626-32.
[http://dx.doi.org/10.4161/psb.3.9.6686] [PMID: 19513253]
[23]
Cohen SD, Tarara JM, Gambetta GA, Matthews MA, Kennedy JA. Impact of diurnal temperature variation on grape berry development, proanthocyanidin accumulation, and the expression of flavonoid pathway genes. J Exp Bot 2012; 63(7): 2655-65.
[http://dx.doi.org/10.1093/jxb/err449] [PMID: 22268158]
[24]
Farmer EE, Ryan CA. Interplant communication. Airborne methyl jasmonate induces synthesis of proteinase inhibitors in plant leaves. Proc Natl Acad Sci USA 1990; 87(19): 7713-6.
[http://dx.doi.org/10.1073/pnas.87.19.7713] [PMID: 11607107]
[25]
Horbowicz M, Kosson R, Wiczkowski W, Koczkodaj D, Mitrus J. The effect of Methyl Jasmonate on accumulation of 2-phenylethylamine and putrescine in seedlings of common buckwheat (Fagopyrum esculentum). Acta Physiol Plant 2011; 33: 897-903.
[http://dx.doi.org/10.1007/s11738-010-0616-5]
[26]
Hichri I, Barrieu F, Bogs J, Kappel C, Delrot S, Lauvergeat V. Recent advances in the transcriptional regulation of the flavonoid biosynthetic pathway. J Exp Bot 2011; 62(8): 2465-83.
[http://dx.doi.org/10.1093/jxb/erq442] [PMID: 21278228]
[27]
Xu F, Ning Y, Zhang W, et al. An R2R3-MYB transcription factor as a negative regulator of the flavonoid biosynthesis pathway in Ginkgo biloba. Funct Integr Genomics 2014; 14(1): 177-89.
[http://dx.doi.org/10.1007/s10142-013-0352-1] [PMID: 24306138]
[28]
Mellway RD, Tran LT, Prouse MB, Campbell MM, Constabel CP. The wound- pathogen- and ultraviolet B-responsive MYB134 gene encodes an R2R3 MYB transcription factor that regulates proanthocyanidin synthesis in poplar. Plant Physiol 2009; 150(2): 924-41.
[http://dx.doi.org/10.1104/pp.109.139071] [PMID: 19395405]
[29]
D’Archivio M, Filesi C, Varì R, Scazzocchio B, Masella R. Bioavailability of the polyphenols. Status and controversies. Int J Mol Sci 2010; 11(4): 1321-42.
[http://dx.doi.org/10.3390/ijms11041321] [PMID: 20480022]
[30]
Landete JM. Updated knowledge about polyphenols. Functions, bioavailability, metabolism, and health. Crit Rev Food Sci Nutr 2012; 52(10): 936-48.
[http://dx.doi.org/10.1080/10408398.2010.513779] [PMID: 22747081]
[31]
Scalbert A, Morand C, Manach C, Rémésy C. Absorption and metabolism of polyphenols in the gut and impact on health. Biomed Pharmacother 2002; 56(6): 276-82.
[http://dx.doi.org/10.1016/S0753-3322(02)00205-6] [PMID: 12224598]
[32]
Hollman PC, Katan MB. Dietary flavonoids: Intake, health effects and bioavailability. Food Chem Toxicol 1999; 37(9-10): 937-42.
[http://dx.doi.org/10.1016/S0278-6915(99)00079-4] [PMID: 10541448]
[33]
Day AJ, Cañada FJ, Díaz JC, et al. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 2000; 468(2-3): 166-70.
[http://dx.doi.org/10.1016/S0014-5793(00)01211-4] [PMID: 10692580]
[34]
Del Rio D, Borges G, Crozier A. Berry flavonoids and phenolics: Bioavailability and evidence of protective effects. Br J Nutr 2010; 104(Suppl. 3): S67-90.
[http://dx.doi.org/10.1017/S0007114510003958] [PMID: 20955651]
[35]
Manach C, Morand C, Texier O, et al. Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. J Nutr 1995; 125(7): 1911-22.
[http://dx.doi.org/10.1093/jn/125.7.1911] [PMID: 7616308]
[36]
Young JF, Nielsen SE, Haraldsdóttir J, et al. Effect of fruit juice intake on urinary quercetin excretion and biomarkers of antioxidative status. Am J Clin Nutr 1999; 69(1): 87-94.
[http://dx.doi.org/10.1093/ajcn/69.1.87] [PMID: 9925128]
[37]
Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: Chemistry, metabolism and structure-activity relationships. J Nutr Biochem 2002; 13(10): 572-84.
[http://dx.doi.org/10.1016/S0955-2863(02)00208-5] [PMID: 12550068]
[38]
Burda S, Oleszek W. Antioxidant and antiradical activities of flavonoids. J Agric Food Chem 2001; 49(6): 2774-9.
[http://dx.doi.org/10.1021/jf001413m] [PMID: 11409965]
[39]
Amić D, Davidović-Amić D, Beslo D, Rastija V, Lucić B, Trinajstić N. SAR and QSAR of the antioxidant activity of flavonoids. Curr Med Chem 2007; 14(7): 827-45.
[http://dx.doi.org/10.2174/092986707780090954] [PMID: 17346166]
[40]
Zhu M, Fahl WE. Functional characterization of transcription regulators that interact with the electrophile response element. Biochem Biophys Res Commun 2001; 289(1): 212-9.
[http://dx.doi.org/10.1006/bbrc.2001.5944] [PMID: 11708801]
[41]
Nerland DE. The antioxidant/electrophile response element motif. Drug Metab Rev 2007; 39(1): 235-48.
[http://dx.doi.org/10.1080/03602530601125000] [PMID: 17364885]
[42]
Nagata H, Takekoshi S, Takagi T, Honma T, Watanabe K. Antioxidative action of flavonoids, quercetin and catechin, mediated by the activation of glutathione peroxidase. Tokai J Exp Clin Med 1999; 24(1): 1-11.
[PMID: 10530620]
[43]
Martín MÁ, Serrano ABG, Ramos S, Pulido MI, Bravo L, Goya L. Cocoa flavonoids up-regulate antioxidant enzyme activity via the ERK1/2 pathway to protect against oxidative stress-induced apoptosis in hepg2 cells. J Nutr Biochem 2010; 21(3): 196-205.
[http://dx.doi.org/10.1016/j.jnutbio.2008.10.009] [PMID: 19195869]
[44]
Procházková D, Boušová I, Wilhelmová N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia 2011; 82(4): 513-23.
[http://dx.doi.org/10.1016/j.fitote.2011.01.018] [PMID: 21277359]
[45]
Brown JE, Khodr H, Hider RC, Rice-Evans CA. Structural dependence of flavonoid interactions with Cu2+ ions. Implications for their antioxidant properties. Biochem J 1998; 330(Pt 3): 1173-8.
[http://dx.doi.org/10.1042/bj3301173] [PMID: 9494082]
[46]
Kopacz M. Complexes of cadmium (II), mercury (II) and lead (II) with Quercetin-5′-Sulfonic Acid (QSA). Pol J Chem 2003; 77(12): 1777-86.
[47]
Chlebda E, Magdalan J, Merwid-Ląd A, et al. Influence of water-soluble flavonoids, quercetin-5′-sulfonic acid sodium salt and morin-5′-sulfonic acid sodium salt, on antioxidant parameters in the subacute cadmium intoxication mouse model. Exp Toxicol Pathol 2010; 62(2): 105-8.
[http://dx.doi.org/10.1016/j.etp.2009.02.118] [PMID: 19297139]
[48]
Shoskes DA. Effect of bioflavonoids quercetin and curcumin on ischemic renal injury: A new class of renoprotective agents. Transplantation 1998; 66(2): 147-52.
[http://dx.doi.org/10.1097/00007890-199807270-00001] [PMID: 9701255]
[49]
Ursini F, Maiorino M, Morazzoni P, Roveri A, Pifferi G. A novel antioxidant flavonoid (idB 1031) affecting molecular mechanisms of cellular activation. Free Radic Biol Med 1994; 16(5): 547-53.
[http://dx.doi.org/10.1016/0891-5849(94)90054-X] [PMID: 8026797]
[50]
Cos P, Ying L, Calomme M, et al. Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod 1998; 61(1): 71-6.
[http://dx.doi.org/10.1021/np970237h] [PMID: 9461655]
[51]
Korkina LG, Afanas’ev IB. Antioxidant and chelating properties of flavonoids. Adv Pharmacol 1997; 38: 151-63.
[http://dx.doi.org/10.1016/S1054-3589(08)60983-7] [PMID: 8895808]
[52]
Matsuda H, Morikawa T, Ando S, Toguchida I, Yoshikawa M. Structural requirements of flavonoids for nitric oxide production inhibitory activity and mechanism of action. Bioorg Med Chem 2003; 11(9): 1995-2000.
[http://dx.doi.org/10.1016/S0968-0896(03)00067-1] [PMID: 12670650]
[53]
Ali F, Siddique YH. Bioavailability and pharmaco-therapeutic potential of luteolin in overcoming Alzheimer’s disease. CNS Neurol Disord Drug Targets 2019; 18(5): 352-65.
[54]
Shutenko Z, Henry Y, Pinard E, et al. Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion. Biochem Pharmacol 1999; 57(2): 199-208.
[http://dx.doi.org/10.1016/S0006-2952(98)00296-2] [PMID: 9890569]
[55]
van Acker SA, Tromp MN, Haenen GR, van der Vijgh WJF, Bast A. Flavonoids as scavengers of nitric oxide radical. Biochem Biophys Res Commun 1995; 214(3): 755-9.
[http://dx.doi.org/10.1006/bbrc.1995.2350] [PMID: 7575540]
[56]
Tapas AR, Sakarkar DM, Kakde RB. Flavonoids as nutraceuticals: A review. Trop J Pharm Res 2008; 7(3): 1089-99.
[http://dx.doi.org/10.4314/tjpr.v7i3.14693]
[57]
Zhu W, Jia Q, Wang Y, Zhang Y, Xia M. Involvement of a cAMP-PKA-dependent signaling pathway. Free Radic Biol Med 2012; 52(2): 314-27.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.483] [PMID: 22085656]
[58]
Duthie GG, Duthie SJ, Kyle JA. Plant polyphenols in cancer and heart disease: Implications as nutritional antioxidants. Nutr Res Rev 2000; 13(1): 79-106.
[http://dx.doi.org/10.1079/095442200108729016] [PMID: 19087434]
[59]
Lamson DW, Brignall MS, Matthew S, Brignall ND. Antioxidants and cancer, part 3: Quercetin. Altern Med Rev 2000; 5(3): 196-208.
[PMID: 10869101]
[60]
Swinnen JV, Roskams T, Joniau S, et al. Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer 2002; 98(1): 19-22.
[http://dx.doi.org/10.1002/ijc.10127] [PMID: 11857379]
[61]
Sawa T, Nakao M, Akaike T, Ono K, Maeda H. Alkylperoxyl radical-scavenging activity of various flavonoids and other phenolic compounds. Implications for the anti-tumor-promoter effect of vegetables. J Agric Food Chem 1999; 47(2): 397-402.
[http://dx.doi.org/10.1021/jf980765e] [PMID: 10563906]
[62]
Zhao HF, Wang G, Wu CP, et al. A multi-targeted natural flavonoid myricetin suppresses lamellipodia and focal adhesions formation and impedes glioblastoma cell invasiveness and abnormal motility. CNS Neurol Disord Drug Targets 2018; 17(7): 557-67.
[http://dx.doi.org/10.2174/1871527317666180611090006]
[63]
de Oliveira CTP, Colenci R, Pacheco CC, et al. Hydrolyzed rutin decreases worsening of anaplasia in glioblastoma relapse. CNS Neurol Disord Drug Targets 2019; 18(5): 405-12.
[http://dx.doi.org/10.2174/1871527318666190314103104] [PMID: 30868970]
[64]
Mishra A, Sharma AK, Kumar S, Saxena AK, Pandey AK. Bauhinia variegata leaf extracts exhibit considerable antibacterial, antioxidant, and anticancer activities. BioMed Res Int 2013; 2013915436
[http://dx.doi.org/10.1155/2013/915436] [PMID: 24093108]
[65]
Pandey AK, Mishra AK, Mishra A, Kumar S, Chandra A. Therapeutic potential of C. Zeylanicum extracts: An antifungal and antioxidant perspective. Int J Biol Med Res 2010; 1(4): 228-33.
[66]
Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev 1999; 12(4): 564-82.
[http://dx.doi.org/10.1128/CMR.12.4.564] [PMID: 10515903]
[67]
Mishra AK, Mishra A, Kehri HK, Sharma B, Pandey AK. Inhibitory activity of Indian spice plant Cinnamomum zeylanicum extracts against Alternaria solani and Curvularia lunata, the pathogenic dematiaceous moulds. Ann Clin Microbiol Antimicrob 2009; 8(1): 9.
[http://dx.doi.org/10.1186/1476-0711-8-9] [PMID: 19267932]
[68]
Ohemeng KA, Schwender CF, Fu KP, Barrett JF. DNA gyrase inhibitory and antibacterial activity of some flavones. Bioorg Med Chem Lett 1993; 3(2): 225-30.
[http://dx.doi.org/10.1016/S0960-894X(01)80881-7]
[69]
Tsuchiya H, Iinuma M. Reduction of membrane fluidity by antibacterial sophoraflavanone G isolated from Sophora exigua. Phytomedicine 2000; 7(2): 161-5.
[http://dx.doi.org/10.1016/S0944-7113(00)80089-6] [PMID: 10839220]
[70]
Wang S, Ma F, Huang L, et al. Dl-3-n-Butylphthalide (NBP): A promising therapeutic agent for ischemic stroke. CNS Neurol Disord Drug Targets 2000; 17(5): 338-47.
[71]
Calderon Guzman D, Juarez Olguin H, Hernandez Garcia E, Punzo Soto M, Santillan Garcia M, Barragan Mejia G. Natural steroids and androgen antagonists used as neuroprotection in common neurological disorders. CNS Neurol Disord Drug Targets 2017; 16(7): 763-71.
[72]
Crowley G. Utilizing delta opioid receptors and peptides for cytoprotection. Implications in stroke and other neurological disorders. CNS Neurol Disord Drug Targets 2017; 16(4): 414-24.
[73]
Attia A, Ahmed H, Gadelkarim M, et al. Meta-analysis of creatine for neuroprotection against Parkinson’s disease. CNS Neurol Disord Drug Targets 2017; 16(2): 169-75.
[http://dx.doi.org/10.2174/1871527315666161104161855]
[74]
Yoo SJ, Cho B, Moon C, Yu SW, Moon C. Neuroprotective effects of an erythropoietin-derived peptide in PC1 2 cells under oxidative stress. CNS Neurol Disord Drug Targets 2016; 15(8): 927-34.
[http://dx.doi.org/10.2174/1871527315666160813223329]
[75]
Zhao J, Zhu M, Kumar M, et al. A pharmacological appraisal of neuroprotective and neurorestorative flavonoids against neurodegenerative diseases. CNS Neurol Disord Drug Targets 2019; 18(2): 103-14.
[http://dx.doi.org/10.2174/1871527317666181105093834]
[76]
Bombardi Duarte AC, Santana MG, di Camilo Orfali G, de Oliveira CT, Priolli DG. Literature evidence and ARRIVE assessment on neuroprotective effects of flavonols in neurodegenerative diseases’ Models. CNS Neurol Disord Drug Targets 2018; 17(1): 34-42.
[77]
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(6): 583-94.
[http://dx.doi.org/10.1016/S0891-5849(00)00510-4] [PMID: 11295356]
[78]
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(4): 359-65.
[http://dx.doi.org/10.1080/10715769800300401] [PMID: 9860051]
[79]
Luo Y, Smith JV, Paramasivam V, et al. Inhibition of amyloid-β aggregation and caspase-3 activation by the Ginkgo biloba extract egb761. Proc Natl Acad Sci USA 2002; 99(19): 12197-202.
[http://dx.doi.org/10.1073/pnas.182425199] [PMID: 12213959]
[80]
Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT. Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson’s disease. Neuroreport 2001; 12(17): 3871-5.
[http://dx.doi.org/10.1097/00001756-200112040-00053] [PMID: 11726811]
[81]
Joseph JA, Shukitt-Hale B, Denisova NA, et al. Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. J Neurosci 1998; 18(19): 8047-55.
[http://dx.doi.org/10.1523/JNEUROSCI.18-19-08047.1998] [PMID: 9742171]
[82]
Joseph JA, Shukitt-Hale B, Denisova NA, et al. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci 1999; 19(18): 8114-21.
[http://dx.doi.org/10.1523/JNEUROSCI.19-18-08114.1999] [PMID: 10479711]
[83]
Solanki I, Parihar P, Mansuri ML, Parihar MS. Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr 2015; 6(1): 64-72.
[http://dx.doi.org/10.3945/an.114.007500] [PMID: 25593144]
[84]
Nie G, Cao Y, Zhao B. Protective effects of green tea polyphenols and their major component, (-)-epigallocatechin-3-gallate (EGCG), on 6-hydroxydopamine-induced apoptosis in PC12 cells. Redox Rep 2002; 7(3): 171-7.
[http://dx.doi.org/10.1179/135100002125000424] [PMID: 12189048]
[85]
Baluchnejadmojarad T, Roghani M, Nadoushan MRJ, Bagheri M. Neuroprotective effect of genistein in 6-hydroxydopamine hemi-parkinsonian rat model. Phytother Res 2009; 23(1): 132-5.
[http://dx.doi.org/10.1002/ptr.2564] [PMID: 18693302]
[86]
Khan MM, Raza SS, Javed H, et al. Rutin protects dopaminergic neurons from oxidative stress in an animal model of Parkinson’s disease. Neurotox Res 2012; 22(1): 1-15.
[http://dx.doi.org/10.1007/s12640-011-9295-2] [PMID: 22194158]
[87]
Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer JP. The neuroprotective potential of flavonoids: A multiplicity of effects. Genes Nutr 2008; 3(3-4): 115-26.
[http://dx.doi.org/10.1007/s12263-008-0091-4] [PMID: 18937002]
[88]
Mansuri ML, Parihar P, Solanki I, Parihar MS. Flavonoids in modulation of cell survival signalling pathways. Genes Nutr 2014; 9(3): 400.
[http://dx.doi.org/10.1007/s12263-014-0400-z] [PMID: 24682883]
[89]
Simão F, Matté A, Pagnussat AS, Netto CA, Salbego CG. Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK-3β and CREB through PI3-K/Akt pathways. Eur J Neurosci 2012; 36(7): 2899-905.
[http://dx.doi.org/10.1111/j.1460-9568.2012.08229.x] [PMID: 22817531]
[90]
Li FQ, Wang T, Pei Z, Liu B, Hong JS. Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons. J Neural Transm (Vienna) 2005; 112(3): 331-47.
[http://dx.doi.org/10.1007/s00702-004-0213-0] [PMID: 15503194]
[91]
Levites Y, Amit T, Youdim MB, Mandel S. Involvement of protein kinase C activation and cell survival/cell cycle genes in green tea polyphenol (-)-epigallocatechin 3-gallate neuroprotective action. J Biol Chem 2002; 277(34): 30574-80.
[http://dx.doi.org/10.1074/jbc.M202832200] [PMID: 12058035]
[92]
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(4): 1355-67.
[http://dx.doi.org/10.1111/j.1471-4159.2007.04841.x] [PMID: 17961201]
[93]
Zhang Z, Cui W, Li G, et al. Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways. J Agric Food Chem 2012; 60(33): 8171-82.
[http://dx.doi.org/10.1021/jf301511m] [PMID: 22838648]
[94]
Paris D, Mathura V, Ait-Ghezala G, et al. Flavonoids lower Alzheimer’s Aβ production via an NF-κb dependent mechanism. Bioinformation 2011; 6(6): 229-36.
[http://dx.doi.org/10.6026/97320630006229] [PMID: 21738321]
[95]
Capiralla H, Vingtdeux V, Zhao H, et al. Resveratrol mitigates lipopolysaccharide- and Aβ-mediated microglial inflammation by inhibiting the TLR4/NF-κb/STAT signaling cascade. J Neurochem 2012; 120(3): 461-72.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07594.x] [PMID: 22118570]
[96]
Xue X, Qu XJ, Yang Y, et al. Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor κb p65 activation. Biochem Biophys Res Commun 2010; 403(3-4): 398-404.
[http://dx.doi.org/10.1016/j.bbrc.2010.11.042] [PMID: 21093411]
[97]
Patir H, Sarada SKS, Singh S, Mathew T, Singh B, Bansal A. Quercetin as a prophylactic measure against high altitude cerebral edema. Free Radic Biol Med 2012; 53(4): 659-68.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.06.010] [PMID: 22743108]
[98]
Ding BJ, Ma WW, He LL, et al. Soybean isoflavone alleviates β-amyloid 1-42 induced inflammatory response to improve learning and memory ability by down regulation of Toll-like receptor 4 expression and nuclear factor-κb activity in rats. Int J Dev Neurosci 2011; 29(5): 537-42.
[http://dx.doi.org/10.1016/j.ijdevneu.2011.04.002] [PMID: 21515354]
[99]
Shah ZA, Li RC, Ahmad AS, et al. The flavanol (-)-epicatechin prevents stroke damage through the Nrf2/HO1 pathway. J Cereb Blood Flow Metab 2010; 30(12): 1951-61.
[http://dx.doi.org/10.1038/jcbfm.2010.53] [PMID: 20442725]
[100]
Ren J, Fan C, Chen N, Huang J, Yang Q. Resveratrol pretreatment attenuates cerebral ischemic injury by upregulating expression of transcription factor Nrf2 and HO-1 in rats. Neurochem Res 2011; 36(12): 2352-62.
[http://dx.doi.org/10.1007/s11064-011-0561-8] [PMID: 21850487]
[101]
Behrens A, Sibilia M, Wagner EF. Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nat Genet 1999; 21(3): 326-9.
[http://dx.doi.org/10.1038/6854] [PMID: 10080190]
[102]
Ishikawa Y, Kitamura M. Anti-apoptotic effect of Quercetin: Intervention in the JNK- and ERK-mediated apoptotic pathways. Kidney Int 2000; 58(3): 1078-87.
[http://dx.doi.org/10.1046/j.1523-1755.2000.00265.x] [PMID: 10972672]
[103]
Schroeter H, Spencer JP, Rice-Evans C, Williams RJ. Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochem J 2001; 358(Pt 3): 547-57.
[http://dx.doi.org/10.1042/bj3580547] [PMID: 11535118]
[104]
Hwang SL, Yen GC. Modulation of Akt, JNK, and p38 activation is involved in citrus flavonoid-mediated cytoprotection of PC12 cells challenged by hydrogen peroxide. J Agric Food Chem 2009; 57(6): 2576-82.
[http://dx.doi.org/10.1021/jf8033607] [PMID: 19222219]
[105]
Vallés SL, Borrás C, Gambini J, et al. Oestradiol or genistein rescues neurons from amyloid beta-induced cell death by inhibiting activation of p38. Aging Cell 2008; 7(1): 112-8.
[http://dx.doi.org/10.1111/j.1474-9726.2007.00356.x] [PMID: 18031570]
[106]
Zhu LH, Bi W, Qi RB, et al. Luteolin reduces primary hippocampal neurons death induced by neuroinflammation. Neurol Res 2011; 33(9): 927-34.
[http://dx.doi.org/10.1179/1743132811Y.0000000023] [PMID: 22080993]
[107]
Park SE, Sapkota K, Kim S, Kim H, Kim SJ. Kaempferol acts through mitogen-activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells. Br J Pharmacol 2011; 164(3): 1008-25.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01389.x] [PMID: 21449918]
[108]
Lau FC, Bielinski DF, Joseph JA. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. J Neurosci Res 2007; 85(5): 1010-7.
[http://dx.doi.org/10.1002/jnr.21205] [PMID: 17265471]
[109]
Li R, Huang YG, Fang D, Le WD. (-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J Neurosci Res 2004; 78(5): 723-31.
[http://dx.doi.org/10.1002/jnr.20315] [PMID: 15478178]
[110]
Chen C, Zhou J, Ji C. Quercetin: A potential drug to reverse multidrug resistance. Life Sci 2010; 87(11-12): 333-8.
[http://dx.doi.org/10.1016/j.lfs.2010.07.004] [PMID: 20637779]
[111]
Rendeiro C, Vauzour D, Rattray M, et al. Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor. PLoS One 2013; 8(5)e63535
[http://dx.doi.org/10.1371/journal.pone.0063535] [PMID: 23723987]
[112]
Conboy L, Foley AG, O’Boyle NM, et al. Curcumin-induced degradation of PKC δ is associated with enhanced dentate NCAM PSA expression and spatial learning in adult and aged Wistar rats. Biochem Pharmacol 2009; 77(7): 1254-65.
[http://dx.doi.org/10.1016/j.bcp.2008.12.011] [PMID: 19161989]
[113]
Gascon E, Vutskits L, Kiss JZ. The role of PSA-NCAM in adult neurogenesis Structure and function of the neural cell adhesion molecule NCAM. New York: Springer 2010; pp. 127-36.
[http://dx.doi.org/10.1007/978-1-4419-1170-4_8]
[114]
Tripoli E, La Guardia M, Giammanco S, Di Majo D, Giammanco M. Citrus flavonoids: Molecular structure, biological activity and nutritional properties: A review. Food Chem 2007; 104: 466-79.
[http://dx.doi.org/10.1016/j.foodchem.2006.11.054]
[115]
Hertog MG, Hollman PC, Katan MB. Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. J Agric Food Chem 1992; 40: 2379-83.
[http://dx.doi.org/10.1021/jf00024a011]
[116]
Keys A. Mediterranean diet and public health: Personal reflections. Am J Clin Nutr 1995; 61(6): 1321S-3S.
[http://dx.doi.org/10.1093/ajcn/61.6.1321S] [PMID: 7754982]
[117]
Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: The Zutphen Elderly Study. Lancet 1993; 342(8878): 1007-11.
[http://dx.doi.org/10.1016/0140-6736(93)92876-U] [PMID: 8105262]
[118]
Yao LH, Jiang YM, Shi J, et al. Flavonoids in food and their health benefits. Plant Foods Hum Nutr 2004; 59(3): 113-22.
[http://dx.doi.org/10.1007/s11130-004-0049-7] [PMID: 15678717]
[119]
Ejaz S, Ejaz A, Matsuda K, Lim CW. Limonoids as cancer chemopreventive agents. J Sci Food Agric 2006; 86: 339-45.
[http://dx.doi.org/10.1002/jsfa.2396]
[120]
Horowitz RM, Gentili B. Flavonoid constituents of citrus. Citrus Sci Technol 1977; 1: 397-426.
[121]
Gionfriddo F, Postorino E, Bovalo FI. Flavanoni glucosidici del succo di bergamotto. Essenze Deriv Agrum 1996; 66: 404-16.
[122]
Macheix JJ, Fleuriet A, Billot J. Changes and metabolism of phenolic compounds in fruits. Fruit Phenolics 1990; pp. 149-221.
[123]
Mouly P, Gaydou EM, Auffray A. Simultaneous separation of flavanone glycosides and polymethoxylated flavones in citrus juices using liquid chromatography. J Chromatogr A 1998; 800(2): 171-9.
[http://dx.doi.org/10.1016/S0021-9673(97)01131-X] [PMID: 9561761]
[124]
Yusof S, Ghazali HM, King GS. Naringin content in local citrus fruits. Food Chem 1990; 37: 113-21.
[http://dx.doi.org/10.1016/0308-8146(90)90085-I]
[125]
Kroyer G. The antioxidant activity of citrus fruit peels. Z Ernahrungswiss 1986; 25(1): 63-9.
[http://dx.doi.org/10.1007/BF02023620] [PMID: 3727631]
[126]
Pratt DE, Hudson BJ. Food antioxidants. Dordrecht: Springer 1990; pp. 171-91.
[http://dx.doi.org/10.1007/978-94-009-0753-9_5]
[127]
Benavente Garcia O, Castillo J, Sabater F, Del Rio JA. Characterization of a S-adenosyl-L-methionine: Eriodictyol 4′-O-methyltrans-ferase from Citrus aurantium developmental changes in the levels of 4′-O-methoxyflavonoids and S-adenosyl-L-methionine: Eriodictyol 4′-O-methyltransferase activity. Plant Physiol Biochem 1995; 33(3): 263-71.
[128]
Horowitz RM. Taste effects of flavonoids. Prog Clin Biol Res 1986; 213: 163-75.
[PMID: 3520586]
[129]
Marini D, Balestrieri F. Multivariate analysis of flavanone glycosides in citrus juices. Ital J Food Sci 1995; 7(3): 255-64.
[130]
Ooghe WC, Detavernier CLM. Detection of the addition of Citrus reticulata and hybrids to Citrus sinensis by flavonoids. J Agric Food Chem 1997; 45: 1633-7.
[http://dx.doi.org/10.1021/jf9606262]
[131]
Bocco A, Cuvelier ME, Richard H, Berset C. Antioxidant activity and phenolic composition of citrus peel and seed extracts. J Agric Food Chem 1998; 46: 2123-9.
[http://dx.doi.org/10.1021/jf9709562]
[132]
Mouly PP, Gaydou EM, Faure R, Estienne JM. Blood orange juice authentication using cinnamic acid derivatives. Variety differentiations associated with flavanone glycoside content. J Agric Food Chem 1997; 45: 373-7.
[http://dx.doi.org/10.1021/jf9605097]
[133]
Benavente-García O, Castillo J, Marin FR, Ortuño A, Del Río JA. Uses and properties of citrus flavonoids. J Agric Food Chem 1997; 45: 4505-15.
[http://dx.doi.org/10.1021/jf970373s] [PMID: 18593176]
[134]
Hung WL, Chang WS, Lu WC, et al. Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat. Yao Wu Shi Pin Fen Xi 2018; 26(2): 849-57.
[http://dx.doi.org/10.1016/j.jfda.2017.08.003] [PMID: 29567257]
[135]
Nogata Y, Sakamoto K, Shiratsuchi H, Ishii T, Yano M, Ohta H. Flavonoid composition of fruit tissues of citrus species. Biosci Biotechnol Biochem 2006; 70(1): 178-92.
[http://dx.doi.org/10.1271/bbb.70.178] [PMID: 16428836]
[136]
Feng X, Zhang Q, Cong P, Zhu Z. Simultaneous determination of flavonoids in different citrus fruit juices and beverages by high-performance liquid chromatography and analysis of their chromatographic profiles by chemometrics. Anal Methods 2012; 4: 3748-53.
[http://dx.doi.org/10.1039/c2ay25562f]
[137]
Yi Z, Yu Y, Liang Y, Zeng B. In vitro antioxidant and antimicrobial activities of the extract of Pericarpium citri reticulatae of a new Citrus cultivar and its main flavonoids. Food Sci Technol 2008; 41: 597-603.
[http://dx.doi.org/10.1016/j.lwt.2007.04.008]
[138]
So FV, Guthrie N, Chambers AF, Moussa M, Carroll KK. Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 1996; 26(2): 167-81.
[http://dx.doi.org/10.1080/01635589609514473] [PMID: 8875554]
[139]
Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M. HL-60 differentiating activity and flavonoid content of the readily extractable fraction prepared from citrus juices. J Agric Food Chem 1999; 47(1): 128-35.
[http://dx.doi.org/10.1021/jf9805101] [PMID: 10563860]
[140]
Hashida K, Kitao Y, Sudo H, et al. ATF6alpha promotes astroglial activation and neuronal survival in a chronic mouse model of Parkinson’s disease. PLoS One 2012; 7(10)e47950
[http://dx.doi.org/10.1371/journal.pone.0047950] [PMID: 23112876]
[141]
Shu Z, Yang B, Zhao H, et al. Tangeretin exerts anti-neuroinflammatory effects via NF-κB modulation in lipopolysac-charide-stimulated microglial cells. Int Immunopharmacol 2014; 19(2): 275-82.
[http://dx.doi.org/10.1016/j.intimp.2014.01.011] [PMID: 24462494]
[142]
Yang JS, Wu XH, Yu HG, Teng LS. Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease dementia in rats. Inflammopharmacology 2017; 25(4): 471-84.
[http://dx.doi.org/10.1007/s10787-017-0348-x] [PMID: 28577132]
[143]
Yao X, Zhu X, Pan S, et al. Antimicrobial activity of nobiletin and tangeretin against Pseudomonas. Food Chem 2012; 132: 1883-90.
[http://dx.doi.org/10.1016/j.foodchem.2011.12.021]
[144]
Xu MS, Chen S, Wang WQ, Liu SQ. Employing bifunctional enzymes for enhanced extraction of bioactives from plants: Flavonoids as an example. J Agric Food Chem 2013; 61(33): 7941-8.
[http://dx.doi.org/10.1021/jf402125y] [PMID: 23869387]
[145]
Pan MH, Chen WJ, Lin-Shiau SY, Ho CT, Lin JK. Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating CDK inhibitors p21 and p27 in human colorectal carcinoma cells. Carcinogenesis 2002; 23(10): 1677-84.
[http://dx.doi.org/10.1093/carcin/23.10.1677] [PMID: 12376477]
[146]
Morley KL, Ferguson PJ, Koropatnick J. Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells. Cancer Lett 2007; 251(1): 168-78.
[http://dx.doi.org/10.1016/j.canlet.2006.11.016] [PMID: 17197076]
[147]
Meiyanto E, Hermawan A, Anindyajati A. Natural products for cancer-targeted therapy: Citrus flavonoids as potent chemopreventive agents. Asian Pac J Cancer Prev 2012; 13(2): 427-36.
[http://dx.doi.org/10.7314/APJCP.2012.13.2.427] [PMID: 22524801]
[148]
Vaiyapuri S, Ali MS, Moraes LA, et al. Tangeretin regulates platelet function through inhibition of phosphoinositide 3-kinase and cyclic nucleotide signaling. Arterioscler Thromb Vasc Biol 2013; 33(12): 2740-9.
[http://dx.doi.org/10.1161/ATVBAHA.113.301988] [PMID: 24135020]
[149]
Nagase H, Omae N, Omori A, et al. Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities. Biochem Biophys Res Commun 2005; 337(4): 1330-6.
[http://dx.doi.org/10.1016/j.bbrc.2005.10.001] [PMID: 16253614]
[150]
Yang EJ, Lim SH, Song KS, Han HS, Lee J. Identification of active compounds from Aurantii Immatri Pericarpium attenuating brain injury in a rat model of ischemia-reperfusion. Food Chem 2013; 138(1): 663-70.
[http://dx.doi.org/10.1016/j.foodchem.2012.09.137] [PMID: 23265538]
[151]
Fatima A, Khanam S, Rahul R, et al. Protective effect of tangeritin in transgenic Drosophila model of Parkinson’s disease. Front Biosci (Elite Ed) 2017; 9: 44-53.
[http://dx.doi.org/10.2741/e784] [PMID: 27814588]
[152]
Liang F, Fang Y, Cao W, et al. Tangeretin attenuates tert-Butyl Hydroperoxide (t-BHP)-induced oxidative damage in HEPG2 cells: Relevance of Nrf2/ARE and MAPKS signaling pathways. J Agric Food Chem 2018; 66(25): 6317-25.
[http://dx.doi.org/10.1021/acs.jafc.8b01875] [PMID: 29871486]
[153]
Wang M, Meng D, Zhang P, et al. Antioxidant protection of nobiletin, 5-demethylnobiletin, tangeretin, and 5-demethyltangeretin from citrus peel in Saccharomyces cerevisiae. J Agric Food Chem 2018; 66(12): 3155-60.
[http://dx.doi.org/10.1021/acs.jafc.8b00509] [PMID: 29526093]
[154]
Braidy N, Behzad S, Habtemariam S, et al. Neuroprotective effects of citrus fruit-derived flavonoids, nobiletin and tangeretin in Alzheimer’s and Parkinson’s disease. CNS Neurol Disord Drug Targets 2017; 16(4): 387-97.
[http://dx.doi.org/10.2174/1871527316666170328113309] [PMID: 28474543]
[155]
Chen HF, Zhang WG, Yuan JB, Li YG, Yang SL, Yang WL. Simultaneous quantification of polymethoxylated flavones and coumarins in Fructus aurantii and Fructus aurantii immaturus using HPLC-ESI-MS/MS. J Pharm Biomed Anal 2012; 59: 90-5.
[http://dx.doi.org/10.1016/j.jpba.2011.10.013] [PMID: 22071443]
[156]
Nielsen SE, Breinholt V, Justesen U, Cornett C, Dragsted LO. In vitro biotransformation of flavonoids by rat liver microsomes. Xenobiotica 1998; 28(4): 389-401.
[http://dx.doi.org/10.1080/004982598239498] [PMID: 9604302]
[157]
Canivenc-Lavier MC, Vernevaut MF, Totis M, Siess MH, Magdalou J, Suschetet M. Comparative effects of flavonoids and model inducers on drug-metabolizing enzymes in rat liver. Toxicology 1996; 114(1): 19-27.
[http://dx.doi.org/10.1016/S0300-483X(96)03412-9] [PMID: 8931757]
[158]
Breinholt V, Lauridsen ST, Dragsted LO. Differential effects of dietary flavonoids on drug metabolizing and antioxidant enzymes in female rat. Xenobiotica 1999; 29(12): 1227-40.
[http://dx.doi.org/10.1080/004982599237903] [PMID: 10647909]
[159]
Nielsen SE, Breinholt V, Cornett C, Dragsted LO. Biotransformation of the citrus flavone tangeretin in rats. Identification of metabolites with intact flavane nucleus. Food Chem Toxicol 2000; 38(9): 739-46.
[http://dx.doi.org/10.1016/S0278-6915(00)00072-7] [PMID: 10930694]
[160]
Wei GJ, Hwang LS, Tsai CL. Absolute bioavailability, pharmacokinetics and excretion of 5, 7, 3′, 4′-tetramethoxyflavone in rats. J Funct Foods 2014; 7: 136-41.
[http://dx.doi.org/10.1016/j.jff.2013.10.006]
[161]
Wen X, Walle T. Methylated flavonoids have greatly improved intestinal absorption and metabolic stability. Drug Metab Dispos 2006; 34(10): 1786-92.
[http://dx.doi.org/10.1124/dmd.106.011122] [PMID: 16868069]
[162]
Walle T, Ta N, Kawamori T, Wen X, Tsuji PA, Walle UK. Cancer chemopreventive properties of orally bioavailable flavonoids--methylated versus unmethylated flavones. Biochem Pharmacol 2007; 73(9): 1288-96.
[http://dx.doi.org/10.1016/j.bcp.2006.12.028] [PMID: 17250812]
[163]
Murakami A, Koshimizu K, Ohigashi H, et al. Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin. Biofactors 2002; 16(3-4): 73-82.
[http://dx.doi.org/10.1002/biof.5520160303] [PMID: 14530595]
[164]
Dorta DJ, Pigoso AA, Mingatto FE, et al. Antioxidant activity of flavonoids in isolated mitochondria. Phytother Res 2008; 22(9): 1213-8.
[http://dx.doi.org/10.1002/ptr.2441] [PMID: 18729257]
[165]
Lagoa R, Graziani I, Lopez-Sanchez C, Garcia-Martinez V, Gutierrez-Merino C. Complex I and cytochrome c are molecular targets of flavonoids that inhibit hydrogen peroxide production by mitochondria. Biochim Biophys Acta 2011; 1807(12): 1562-72.
[166]
Elingold I, Isollabella MP, Casanova MB, Celentano AM, Pérez C, Cabrera JL. Mitochondrial toxicity and antioxidant activity of a prenylated flavonoid isolated from Dalea elegans. Chem Biol Interact 2008; 171(3): 294-305.
[167]
Dorta DJ, Pigoso AA, Mingatto FE, et al. The interaction of flavonoids with mitochondria effects on energetic processes. Chem Biol Interact 2005; 152(2-3): 67-78.
[168]
Mcdonald L, Liu B, Taraboletti A, et al. Fluorescent flavonoids for endoplasmic reticulum cell imaging. J Mater Chem B 2016; 4(48): 7902-8.
[169]
Kim DS, Kwon DY, Kim MS, et al. The involvement of endoplasmic reticulum stress in flavonoid-induced protection on cardiac cell death caused by ischaemia/reperfusion. J Pharm Pharmacol 2010; 62(2): 197-204.
[http://dx.doi.org/10.1211/jpp.62.02.0007] [PMID: 20487199]
[170]
Kuo SM. Flavonoids and gene expression in mammalian cells. Adv Exp Med Biol 2002; 505: 191-200.
[http://dx.doi.org/10.1007/978-1-4757-5235-9_18] [PMID: 12083463]
[171]
Moskot M, Jakóbkiewicz-Banecka J, Smolińska E, Piotrowska E, Węgrzyn G, Gabig-Cimińska M. Effects of flavonoids on expression of genes involved in cell cycle regulation and DNA replication in human fibroblasts. Mol Cell Biochem 2015; 407(1-2): 97-109.
[http://dx.doi.org/10.1007/s11010-015-2458-3] [PMID: 26003441]
[172]
Giuliani C, Noguchi Y, Harii N, et al. The Flavonoid quercetin regulates growth and gene expression in rat FRTL-5 thyroid cells. Endocrinology 2008; 149(1): 84-92.
[http://dx.doi.org/10.1210/en.2007-0618] [PMID: 17962351]
[173]
Xu H, Luo J, Huang J, Wen Q. Flavonoids intake and risk of type 2 diabetes mellitus: A meta-analysis of prospective cohort studies. Medicine (Baltimore) 2018; 97(19)e0686
[http://dx.doi.org/10.1097/MD.0000000000010686] [PMID: 29742713]
[174]
Lin JJ, Huang CC, Su YL, et al. Proteomics analysis of tangeretin-induced apoptosis through mitochondrial dysfunction in bladder cancer cells. Int J Mol Sci 2019.
[http://dx.doi.org/10.3390/ijms20051017]
[175]
Ma LL, Wang DW, Yu XD, Zhou YL. Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells. Biomed Pharmacother 2016; 81: 491-6.
[http://dx.doi.org/10.1016/j.biopha.2016.04.006] [PMID: 27261630]
[176]
Kou G, Li Z, Wu C, et al. Citrustangeretin improves skeletal muscle mitochondrial biogenesis via activating the AMPK-PGC1-α pathway in vitro and in vivo: A possible mechanism for its beneficial effect on physical performance. J Agric Food Chem 2018; 66(45): 11917-25.
[177]
Vernarelli JA, Lambert JD. Flavonoid intake is inversely associated with obesity and C-reactive protein, a marker for inflammation, in US adults. Nutr Diabetes 2017; 7(5)e276
[178]
Martins IJ. In: Frontiers in Clinical Drug Research CNS and Neurological Disorders, Atta-ur-Rahman, Eds. UAE 2015: Bentham Science Publishers; pp. 158-192.
[179]
Martins I. Anti-aging genes improve appetite regulation and reverse cell senescence and apoptosis in global populations. Adv Aging Res 2016; 5: 9-26.
[http://dx.doi.org/10.4236/aar.2016.51002]
[180]
Pisonero-Vaquero S, González-Gallego J, Sánchez-Campos S, García-Mediavilla MV. Flavonoids and related compounds in non-alcoholic fatty liver disease therapy. Curr Med Chem 2015; 22(25): 2991-3012.
[http://dx.doi.org/10.2174/0929867322666150805094940] [PMID: 26242257]
[181]
Van De Wier B, Koek GH, Bast A. Haenengr.The potential of flavonoids in the treatment of non-alcoholic fatty liver disease. Crit Rev Food Sci Nutr 2017; 57(4): 834-55.
[182]
Shin JH, Jung JH. Non-alcoholic fatty liver disease and flavonoids: Current perspectives. Clin Res Hepatol Gastroenterol 2017; 41(1): 17-24.
[http://dx.doi.org/10.1016/j.clinre.2016.07.001] [PMID: 27545758]
[183]
Martins IJ. Induction of NAFLD with increased risk of obesity and chronic diseases in developed countries. Open J Endocr Metab Dis 2014; 4: 90-110.
[http://dx.doi.org/10.4236/ojemd.2014.44011]
[184]
Martins I. Nutrition increases survival and reverses NAFLD and Alzheimers disease Anti-aging diets reverse insulin resistance and improves thinking and intelligence with close links to chronic diseases. Mauritius: LAP LAMBERT Academic Publishing 2015; p. 168.
[185]
Martins IJ, Creegan R. Links between insulin resistance, lipoprotein metabolism and amyloidosis in Alzheimer’s disease. Health 2014; 6(12): 47483.
[186]
Spagnuolo C, Moccia S, Russo GL. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur J Med Chem 2018; 153(153): 105-15.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.001] [PMID: 28923363]
[187]
Costa SL, Silva VD, Dos Santos Souza C, et al. Impact of plant-derived flavonoids on neurodegenerative diseases. Neurotox Res 2016; 30(1): 41-52.
[http://dx.doi.org/10.1007/s12640-016-9600-1] [PMID: 26951456]
[188]
Spencer JP. Flavonoids and brain health: Multiple effects underpinned by common mechanisms. Genes Nutr 2009; 4(4): 243-50.
[http://dx.doi.org/10.1007/s12263-009-0136-3] [PMID: 19685255]
[189]
Matias I, Buosi AS, Gomes FC. Functions of flavonoids in the central nervous system: Astrocytes as targets for natural compounds. Neurochem Int 2016; 95: 85-91.
[190]
Fatima A. Rahul, Siddique YH. Role of tangeritin against cognitive impairments in transgenic Drosophila model of Parkinson’s disease. Neurosci Lett 2019; 705: 112-7.
[http://dx.doi.org/10.1016/j.neulet.2019.04.047] [PMID: 31039425]


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VOLUME: 18
ISSUE: 8
Year: 2019
Page: [581 - 597]
Pages: 17
DOI: 10.2174/1871527318666190916141934
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