Nano-medicine improving the bioavailability of small molecules for the prevention of neurodegenerative diseases

Current Pharmaceutical Design

Volumn 23, Issue 13, 2017, Pages 1897-1908

  Martino, Piera Di ^a   Censi, Roberta ^a   Gigliobianco, Maria Rosa ^a   Zerrillo, Luana ^b   Magnoni, Federico ^a   Agas, Dimitrios ^a   Quaglia, Wilma ^a   Lupidi, Giulio ^a  

^a UNIVERSITY OF CAMERINO   (Italy)

^b LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Curcumin; Folic acid; Gingko biloba; Nanomedicine; Neurodegenerative diseases; Prevention; Quercetin

Indexed keywords

CURCUMIN; FLAVONOID; FOLIC ACID; GINKGO BILOBA EXTRACT; LEVODOPA; LIPOSOME; NANOCARRIER; NANOLIPOSOME; NIOSOME; PLACEBO; QUERCETIN; SOLID LIPID NANOPARTICLE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; BLOOD BRAIN BARRIER; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CHRONIC DISEASE; DEGENERATIVE DISEASE; DNA POLYMORPHISM; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BRAIN LEVEL; DRUG CHOICE; DRUG DOSAGE FORM COMPARISON; DRUG EFFICACY; DRUG FORMULATION; DRUG MECHANISM; DRUG PENETRATION; DRUG RETENTION; DRUG SAFETY; DRUG SOLUBILITY; DRUG STRUCTURE; FOLIC ACID DEFICIENCY; HUMAN; INFLAMMATION; LIFESTYLE; LIVER DISEASE; MALIGNANT NEOPLASM; NANOENCAPSULATION; NANOMEDICINE; NERVE CELL NECROSIS; NEUROPATHOLOGY; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PERIPHERAL ISCHEMIA; PRIORITY JOURNAL; REVIEW; RISK REDUCTION; SINUSITIS; WOUND; ANIMAL; BIOAVAILABILITY; METABOLISM; MOLECULAR LIBRARY; PHARMACOLOGY;

ANIMALS; BIOLOGICAL AVAILABILITY; HUMANS; NANOMEDICINE; NEURODEGENERATIVE DISEASES; SMALL MOLECULE LIBRARIES;

EID: 85021298399     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612822666161227154447     Document Type: Review

References (185)

1. Olesen J, Gustavsson A, Svensson M, Wittchen HU, Jönsson B. The economic cost of brain disorders in Europe. Eur J Neurol 2012; 19(1): 155-62.
2. Soni A. Anxiety and Mood Disorders: Use and Expenditures for Adults 18 and Older, U.S. Civilian Noninstitutionalized Population. Medical Expenditure Panel Survey, Agency for Healthcare Research and Quality, 2007.
3. Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary costs of dementia in the United States. N Engl J Med 2013; 368: 1326-34.
4. Hogan MF. Assessing the economic costs of serious mental illness. Am J Psychiatry 2008; 165: 663-5.
5. Rice DP. Economic Costs of Substance Abuse, 1995. Proc Assoc Am Phys 1999; 111(2): 119-25.
6. Office of National Drug Control Policy (ONDCP). The Economic Costs of Drug Abuse in the United States 1992-1998. NCJ-190636, 2001.
7. Harwood H. Updating Estimates of the Economic Costs of Alcohol Abuse in the United States: Estimates, Update Methods, and Data. Report prepared by The Lewin Group for the National Institute on Alcohol Abuse and Alcoholism, 2000. Based on estimates, analyses, and data reported in Harwood H, Fountain D, and Livermore G. The Economic Costs of Alcohol and Drug Abuse in the United States, 1992. Report prepared for the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, NIH Publication No. 98-4327, Rockville, MD, National Institutes of Health, 1998.
8. Ovbiagele B, Goldstein LB, Higashida RT, et al. Forecasting the future of stroke in the United States. A policy statement from the American Heart Association and American Stroke Association. Stroke 2013; 44: 2361-75.
9. Goldberg LD. The cost of migraine and its treatment. Am J Manag care 2005; 11: S62-67.
10. Adelman G, Rane SG, Villa KF. The cost burden of multiple sclerosis in the United States: a systematic review of the literature. J Med Econ 2013; 16: 639-47.
11. Kowal SL, Dall TM, Chakrabati R, Storm MV, Jain A. The current and projected economic burden of Parkinson’s disease in the United States. Mov Disord 2013; 28: 311-8.
12. Begley CE, Famulari M, Annegers JF, et al. The cost of epilepsy in the United States: an estimate from population-based clinical and survey data. Epilepsia 2000; 41: 342-51.
13. Larkindale J, Yang W, Hogan PF, et al. Cost of illness for neuromuscular diseases in the U.S. Muscle Nerve 2014; 49: 431-8.
14. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown Ml. Projection of the cost of cancer care in the Unites States: 2010-2020. J Natl Cancer Inst 2011; 103: 117-28.
15. Samnaliev M, LeAnn Noh H, Sonneville KR, Austin SB. The economic burden of eating disorders and related mental helath comorbidities: an exploratory analysis using the U.S. Medical Expenditures Panel Survey. Prev Med Rep 2015; 2: 32-34.
16. World Health Organization. (WHO 2011a). Global status report on non-communicable diseases 2010. Geneva: WHO.
17. World Health Organization. (WHO 2008). The Global Burden of Disease: 2004 Update.
18. Whiteford HA, Degenhardt L, Rehm J, et al. Global burden of disease attributable to mental and substance use disorders: findings from Global Burden of Disease Study 2010. The Lancet 2013; 382: 1575-86.
19. Prince M, Guerchet M, Prina M. The epidemiology and impact of dementia: current state and future trends. Geneva: World Health Organization; 2015.
20. Prince M, Guerchet M, Prina M, Alzheimer’s Disease International. Policy Brief for Heads of Government: The Global Impact of Dementia 2013-2050. London: Alzheimer’s Disease International; 2013.
21. Orr HT, Zoghbi HY. Reversing neurodegeneration: a promise unfolds. Cell 2000; 101: 1-4.
22. Selkoe DJ. Preventing Alzheimer’s disease. Science 2012; 337: 1488-92.
23. Solomon A, Mangialasche F, Richard E, et al. Advances in the prevention of Alzheimer’s disease and dementia. J Intern Med 2014; 275: 229-50.
24. Baumgart M, Snyderb HM, Carrillo MC, Fazio S, Kim H, Johns H. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimer’s & Dementia 2015; 11: 718-26.
25. Selkoe DJ. The molecular pathology of Alzheimer’s disease. Neuron 1991; 6: 487-98.
26. Goedert M, Jakes R, Spillantini MG, Hasegawa M, Smith MJ, Crowther RA. Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature 1996; 383: 550-3.
27. Morrison BM, Hof PR, Morrison JH. Determinants of neuronal vulnerability in neurodegenerative diseases. Ann Neurol 1998; 44: (3 Suppl I) S32-S44.
28. Dringemberg HC. Alzheimer’s disease: more than a “cholinergic disorder”-Evidence that cholinergic-monoaminergic interactions contribute to EEG slowing and dementia. Behav Brain Res 2000; 115: 235-49.
29. Buccafusco JJ, Terry AV. Multiple central nervous system targets for eliciting beneficial effects on memory and cognition. J Pharmacol Exp Ther 2000; 295: 438-46.
30. Akiyama H, Barger S, Barnum S, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging 2000; 21(3): 383-421.
31. Klegeris A, McGeer EG, McGeer PL. Therapeutic approaches to inflammation in neurodegenerative disease. Curr Op Neurol 2007; 20: 351-7.
32. Cartier L, Hartley O, Dubois-Dauphin M, Krause KH. Chemokine receptors in the central nervous systems: role in brain inflammation and neurodegenerative diseases. Brain Res Rev 2005; 48: 16-42.
33. The Canadian Study of Health and Aging: risk factors for Alzheimer’s disease in Canada. Neurology 1994; 44(11): 2073-80.
34. Andersen K, Launer LJ, Ott A, Hoes AW, Breteler MM, Hofman A. Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer’s disease? The Rotterdam Study. Neurology 1995; 45(8): 1441-5.
35. Aisen PS, Schafer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 2003; 289(21): 2819-26.
36. Markesbery WR. The role of oxidative stress in Alzheimer disease. Arch Neurol 1999; 56: 1449-52.
37. Christen Y. Oxidative stress an Alzheimer disease. Am J Clin Nutr 2000; 71(Suppl): 621S-9S.
38. Beal MF. Aging, energy and oxidative stress in neurodegerìnerative disorders. Ann Neurol 1995; 38: 357-66.
39. Samii A, Nutt JG, Ransom BR. Parkinson’s disease. Lancet 2004; 363: 1783-193.
40. Bohnen NI, Albin RL. The cholinergic system and Parkinson disease. Behav Brain Res 2011; 221: 564-73.
41. Blandini F, Porter RH, Greenamyre JT. Glutamate and Parkinson’s disease. Mol Neurobiol 1996; 12: 73-94.
42. Prusiner SB. Prion diseases and the BSE crisis. Science 1997; 278: 245-51.
43. Will RG, Alpers MP, Dormont D, Schonberger LB, Tateishi J. Infectious and sporadic prion diseases. In: Prusiner SB, ed. Prion biology and diseases. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 1999: 465-507.
44. Prusiner SB. Shattuck Lecture. Neurodegenerative diseases and prions. N Engl J Med 2001; 344: 1516-26.
45. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from citchen to clinic. Biochem Pharmacol 2008; 75: 787-809.
46. Indira Priyadarsini K. Chemical and structural features influencing the biological activity of curcumin. Curr Pharm Des 2013; 19: 2093-100.
47. Ganguli M, Chandra V, Kamboh MI, et al. Apolipoprotein E polymorphism and Alzheimer disease: the Indo-US cross-national dementia study. Arch Neurol 2000; 57: 824-30.
48. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer’s disease. Curr Alzheimer Res 2005; 2: 1567-72.
49. Kim DS, Park SY, Kim JK. Curcuminoids from Curcuma longa L. (Zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from betaA(1-42) insult. Neurosci Lett 2001; 303: 57-61.
50. Reddy AC, Lokesh BR. Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes. Mol Cell Biochem 1992; 111: 117-24.
51. Sreejayan, RMN. Curcuminoids as potent inhibitors of lipid peroxidation. J Pharm Pharmacol 1994; 46: 1013-6.
52. Shih CA, Lin JK. Inhibition of 8-hydroxydeoxyguanosine formation by curcumin in mouse fibroblast cells. Carcinogenesis 1993; 14: 709-12.
53. Ammon HP, Safayhi H, Mack T, Sabieraj J. Mechanism of antiinflammatory actions of curcumine and boswellic acids. J Ethnopharmacol 1993; 38: 113-9.
54. Xu YX, Pindolia KR, Janakiraman N, Chapman RA, Gautam SC. Curcumin inhibits IL1 alpha and TNF-alpha induction of AP-1 and NF-kB DNA-binding activity in bone marrow stromal cells. Hematopathol Mol Hematol 1997; 11: 49-62.
55. Pan MH, Lin-Shiau SY, Lin JK. Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages. Biochem Pharmacol 2000; 60: 1665-76.
56. Ono K, Hasegawa K, Naiki H, Yamada M. Curcumin has potent anti-amyloidogenic effects for Alzheimer’s beta-amyloid fibrils in vitro. J Neurosci Res 2004; 75: 742-50.
57. Kayed R, Head E, Thompson JL, et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 2003; 300: 486-9.
58. Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ. Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem 2007; 102: 1095-104.
59. Reinke AA, Gestwicki JE. Structure-activity relationships of amyloid beta-aggregation inhibitors based on curcumin: influence of linker length and flexibility. Chem Biol Drug Des 2007; 70: 206-15.
60. Masuda Y, Fukuchi M, Yatagawa T, et al. Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid ß-protein fibrils. Bioorg Med Chem 2011; 19: 5967-74.
61. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neuosci 2001; 21: 8370-7.
62. Kelloff GJ, Crowell JA, Hawk ET, et al. Strategy and planning for chemopreventive drug development: clinical development plans II. J Cell Biochem Suppl 1996; 26: 54-71.
63. Yang K, Lin LC, Tseng TY, Wang SC, Tsai TH. Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. J Chromatogr B: Analyt Technol Biomed Life Sci 2007; 853: 183-9.
64. Kurien BT, Singh A, Matsumoto H, Scofield RH. Improving the solubility and pharmacological efficacy of curcumin by heat treatment. Assay Drug Dev Technol 2007; 5: 567-76.
65. Lin LC, Tsai TH. Curcumin and its nano-formulation: the kinetics of tissue distribution and blood-brain barrier penetration. Int J Pharm 2011; 416: 31-338.
66. Jiang J, Wang W, Sun YJ, Hu M, Li F, Zhu DY. Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing Blood-Brain Barrier damage. Eur J Pharmacol 2007; 561: 54-62.
67. Wang X, Kim JR, Lee SB, et al. Effects of curcuminoids identified in rhizomes of curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease drosophila models. BMC Compl Altern Med 2014; 14: 88.
68. Yallapu MM, Nagesh PKB, Jaggi M, Chauhan SC. Therapeutic applications of curcumin nanoformulations. The AAPS Journal 2015; 17: 1341-56.
69. Mythri RB, Jagatha B, Pradhan N, Andersen J, Bharath MM. Mitochondrial complex I inhibition in Parkinson’s disease: how can curcumin protect mitochondria? Antioxid Redox Signal 2007; 9: 399-408.
70. Ma Z, Shayeganpour A, Brocks DR, Lavasanifar A, Samuel J. Highperformance liquid chromatography analysis of curcumin in rat plasma: application to pharmacokinetics of polymeric micellar formulation of curcumin. Biomed Chromatogr 2007; 21: 546-52.
71. Mohanty C, Sahoo SK. The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. Biomaterials 2010; 31: 6597-611.
72. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm 2007; 4: 807-18.
73. Tsai YM, Chien CF, Lin LC, Tsai TH. Curcumin and its nanoformulation: the kinetics of tissue distribution and blood-brain barrier penetration. Int J Pharm 2011; 416: 331-8
74. Sancini G, Gregori M, Salvati E, et al. Functionalization with TATpeptide enhances blood-brain barrier crossing in vitro of nanoliposomes carrying a curcumin-derivative to bind amyloid-ß peptide. J Nanomed Nanotechnol 2013; 4: 1-8.
75. Sood S, Jain K, Gowthamarajan K. Curcumin-donepezil-loaded nanostructured lipid carriers for intranasal delivery in an Alzheimer’s disease model. Alzheimers Dement 2013; 9: P299.
76. Sun M, Gao Y, Guo C, et al. Enhancement of transport of curcumin to brain in mice by poly(n-butylcyanoacrylate) nanoparticle. J Nanopart Res 2010; 12: 311-22.
77. Feng R, Zhu W, Song Z, Zhao L, Zhai G. Novel star-type methoxy-poly(ethylene glycol) (PEG)-poly(e-caprolactone) (PCL) copolymeric nanoparticles for controlled release of curcumin. J Nanopart Res 2013; 15: 1748.
78. Cheng KK, Yeung CF, Ho SW, Chow SF, Chow AHL, Baum L. Highly stabilized curcumin nanoparticles tested in an in vitro bloodbrain barrier model and in Alzheimer’s disease Tg2576 mice. AAPS J 2013; 15: 324-36.
79. Doggui S, Sahni JK, Arseneault M, Dao L, Ramassamy C. Neuronal uptake and neuroprotective effect of curcumin-loaded PLGA nanoparticles on the human SK-N-SH cell line. J Alzheime’s Dis 2012; 30: 377-92.
80. Le Droumaguet B, Nicolas J, Brambilla D, et al. Versatile and efficient targeting using a single nanoparticulate platform: aplication to cancer and Alzheimer’s disease. ACS Nano 2012; 6: 5866-79.
81. Kakkar V, Muppu SK, Chopra K, Kaur IP. Curcumin loaded solid lipid nanoparticles: an efficient formulation approach for cerebral ischemic reperfusion injury in rats. Eur J Pharm Biopharm 2013; 85 (3 Pt A): 339-45.
82. Mourtas S, Lazar AN, Markoutsa E, Duyckaerts C, Antimisiaris SG. Multifuncional nanoliposomes with curcumin-lipid derivative and brain targeting functionality with potential applications for Alzheimer’s disease. Eur J Med Chem 2014; 80: 175-83.
83. Taylor M, Moore S, Mourtas S, et al. Effect of curcumin-associated and lipid ligand-functionalized nanoliposomes on aggregation of the Alzheimer’s Abeta peptide. Nanomedicine 2011; 7: 541-50.
84. Lazar AN, Mourtas S, Youssef I, et al. Curcumin-conjugated nanoliposomes with high affinity for Abeta deposits: possible applications to Alzheimer disease. Nanomedicine 2013; 9: 712-21.
85. Mourtas S, Canovi M, Zona C, et al. Curcumin-decorated nanoliposomes with very high affinity for amyloid-beta 1-42 peptide. Biomaterials 2011; 32: 1635-45.
86. Croft KD. The chemistry and biological effect of flavonoids ans phenolic acids. Ann NY Acad Sci 1998; 854: 435-42.
87. Pietta PG. Flavonoids as antioxidants. J Nat Prod 2000; 63: 1035-42.
88. Leonarduzzi G, Testa G, Sottero P, Gamba P, Poli G. Design and development of nanovehicle-based delivery systems for preventive or therapeutic supplementation of flavonoides. Curr Med Chem 2010; 17: 74-95.
89. Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nust Biochem 2002; 13: 572-84.
90. Laguerre M, Lecompte J, Villeneuve P. Evaluation of the ability of antioxidants to counteract lipid oxidation: existing methods, new trends anc challenges. Prot Lipid Res 2007; 46: 244-82.
91. Aron PM, Kennedy JA, Flavan-3-ols: nature, occurrence and biological activity. Mol Nutr Food Res 2008; 52: 79-104.
92. Yen GC, Lai HH. Inhibition of reactive nitrogen species effects in vitro and in vivo by isoflavones and soy-based food extracts. J Agric Food Chem 2003; 51: 7892-900.
93. Trujillo M, Ferre-Sueta G, Radi R. Peroxynitrite detoxification and its biological implications. Antioxid Redox Signal 2008; 10: 1607-19.
94. Sugihara N, Arakawa T, Ohnishi M, Furuno K. Anti-and prooxidative effects of flavonoids on metal-induced lipid hydroperoxide-dependent lipid peroxidation in cultured hepatocytes loaded with a-linolenic acid. Free Rad Biol Med 1999; 27: 1313-23.
95. Arora A, Nair MG, Strasburg GM. Structure-activity relationships for antioxidant activities of a series of flavonoids in a liposomial systems. Free Radic Biol Med 1998; 24: 1355-63.
96. García-Lafuente A, Guillamó, E, Villares A, Ristagno MA, Martínez JA. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm Res 2009; 58: 537-52.
97. Biesalki HK. Polyphenols and inlammation: basic interactions. Curr Opin Clin Nutr Metab Care 2007; 10: 724-8.
98. Karin M. Inflammation-activated protein kynases as targets for drug delvelopment. Proc Am Thorac Soc 2005; 2: 386-90.
99. Kim HP, Son KH, Chang HW, Kang SS. Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci 2004; 96: 229-45.
100. Yoon JH, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Mes J 2005; 46: 585-96.
101. Calixto JB, Campos MM, Otuki MF, Santos AR. Antiinflammatory compounds of plant origin. Part II. Modulation of pro-inflammatory cytokines, chemokines and adhesion molecules. Planta Med 2004; 70: 93-103.
102. Huang SM, Wu CH, Yen GC. Effect of flavonoids on the expression of the pro-inflammatory response in human monocytes induced by ligation on the receptor for AGEs. Mol Nutr Food Res 2006; 50: 1129-39.
103. Sharma V, Mishra M, Ghosh S, et al. Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implication in neuroprotection. Brain Res Bull 2007; 73: 55-63.
104. Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT, Swanson PD. Parkinson’s disease risks associated with cigarette smoking, alcohol consuption, and caffeine intake. Am J Epidemiol 2002; 155: 732-8.
105. Lindsay J, Laurin D, Verreault R, et al. Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian study of health and aging. Am J Epidemiol 2002; 156: 912-21.
106. Scaemeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol 2006; 59: 912-21.
107. Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem 2009; 390: 191-214.
108. Pocernich CB, Butterfield DA. Elevation of glutathione as a therapeutic strategy in Alzheimer disease. Biochim Bioph Acta 2012; 1822: 625-30.
109. Myhrstad MC, Carlsen H, Nordström O, Blomhoff R, Moskaug JØ. Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter. Free Radic Biol Med. 2002; 32: 386-93.
110. Zhu JTT, Choi RCY, Chu GKY, et al. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing ß-amyloid-induced cell death. J Agric Food Chem 2007; 55: 2438-45.
111. Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA. Protective effect of quercetin in primary neurons against Abeta(1-42): relevance to Alzheimer’s disease. J Nutr Biochem 2009; 20: 269-75.
112. Cai X, Fang Z, Dou J, Yu A, Zhai G. Bioavailability of quercetin: problems and promises. Curr Med Chem. 2013; 20: 2572-82.
113. Thilakarathna SH, Rupasinghe HPV. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients 2013; 5: 3367-87.
114. Graefe EU, Wittig J, Mueller S, et al. Pharmacokinetics and bioavailability of quercetin glycosides in humans J Clin Pharmacol 2001; 41: 492-9.
115. Youdim KA, Dobbie MS, Kuhnel G, Proteggente AR, Abbott NJ, Rice-Evans C. Interaction betewwn flavonoids an the blood-brain barrier: in vitro studies. J Neurochem 2003; 85: 180-92.
116. Costa G, Abin JA, Dajas F. Nicotine prevents striatal dopamine loss produced by 6-hydroxydopamine lesion in the substantia nigra. Brain Res 2001; 888: 336-42.
117. Youdim KA, Shukitt-Hale B, Joseph JA. Flavonoids and the brain: interactions at the blood-brain barrier and their physioclogical effects on the central nervous system. Free Rad Biol Med 2004; 37: 1683-93.
118. Lin JH, Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 2003; 42: 59-98.
119. Scheepens A, Tan K, Paxton JW. Improving the oral bioavailability of beneficial polyphenols through designed synergies. Genes Nutr 2010; 5: 75-87.
120. Sahni JK, Doggui S, Ali J, et al. Neurotherapeutic applications of nanoparticles in Alzheimer’s disease. J Control Rel 2011; 152: 208-31.
121. Doggui S, Dao L, Ramassamy C. Potential of drug-loaded nanoparticles for Alzheimer’s disease: diagnosis, prevention and treatment. Ther Deliv 2012; 3: 1025-7.
122. Ghosh A, Mandal AK, Sarkar S, Panda S, Das N. Nanoencapsulation of quercetin enhances its dietary efficacy in combating arsenicinduced oxidative damage in liver and brain of rats. Life Sci 2009; 84: 75-80.
123. Testa G, Gamba P, Badilli U, et al. Loading into nanoparticles improbe quercetin’s efficacy in preventing neuroinflammation induced oxysterols. PLOS One 2014; 9: 1-12.
124. Bagad M, Khan ZA. Poly(n-butylcyanoacrylate) nanoparticles for oral delivery of quercetin: preparation, characterization, and pharmacokinetics and biodistribution studies in Wistar rats. Int J Nanomed 2015; 10: 3921-35.
125. Dhawan S, Kapil R, Singh B. Formulation development and systematic optimization of solid lipid nanoparticles of quercetin for improved brain delivery. J Pharm Pharmacol 2011; 63: 342-51.
126. Li H, Zhao X, Ma Y, Zhai G, Li L, Lou H. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J Control Rel 2009; 133: 238-44.
127. Phachonpai W, Wattanathorn J, Muchimapura S, Tong-Un T, Preechagoon D. Neuroprotective effect of quercetin encapsulated liposomes: A novel therapeutic strategy against Alzheimer’s disease. Am J Appl Sci 2010; 7: 480-5.
128. Priprem A, Watanatorn J, Sutthiparinyanont S, Phachonpai W, Muchimapura S. Anxiety and cognitive effects of quercetin liposomes in rats. Nanomedicine 2008; 4: 70-78.
129. Rivera F, Costa G, Abin A, et al. Reduction of ischemic brain damage and increase in glutathione by a liposomal preparation of quercetin in permanent focal ischemia in rats. Neurotox Res 2008; 13: 105-14.
130. Sarkar S, Das N. Mannosylated liposomal flavonoid in combating age-related ischemia-reperfusion induced oxidative damage in rat brain. Mech Ageing Dev 2006; 127: 391-7.
131. Khoee S, Hassanzadeh S, Goliaie B. Effect of hydrophobic drugpolyesteric core interactions on drug loading and release proprieties of poly(ethylene glycol)-polyester-poly(ethylene glycol) triblock core-shell nanoparticles. Nanotechnology 2007; 18: 175602.
132. Wu TH, Yen FL, Lin LT, Tsai TR, Lin CC, Cham TM. Preparation, physicochemical characterization, and antioxidant effects of quercetin nanoparticles. Int J Pharm 2008; 346: 160-8.
133. Sahoo NG, Kakran M, Shaal LA, et al. Preparation and Characterization of quercetin nanocrystals. J Pharm Sci 2010; 100: 2379-90.
134. Le Bars PL. Magnitude of effect and special approach to Ginkgo biloba extract EGb761 in cognitive disorders. Pharmacopsychiatry 2003; 36: S44-9.
135. Smith PF, Maclennan K, Darlington CL. The neuroprotective properties of the Ginkgo biloba leaf a review of the possible relationship to platelet-activating factor (PAF). J Ethnopharmacol 1996; 50: 131-9.
136. Shi C, Zhao L, Zhu B, et al. Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against beta-amyloid peptideinduced toxicity in SH-SY5Y cells. Chem Biol Interact 2009; 181: 115-23.
137. Ellnain-Wojtaszek M, Kruczynski Z, Kasprzak J. Investigation of the free radical scavenging activity of ginkgo biloba l. Leaves. Fitoterapia 2003; 74: 1-6.
138. Goh LM, Barlow PJ, Yong CS. Examination of antioxidant activity of Ginkgo biloba leaf infusions. Food Chem 2003; 82: 275-82.
139. Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M. Antiproliferative activity of flavonoids on several cancer cell lines. Biosci Biotechnol Biochem 1999; 63: 896-9.
140. Oyama Y, Chikahisa L, Ueha T, Kanemaru K, Noda K. Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide. Brain Res 1996; 712: 349-52.
141. Luo Y. Ginkgo biloba neuroprotection: Therapeutic implications in Alzheimer’s disease. J. Alzheimers Dis 2001; 3: 401-7.
142. Ahlemeyer B, Krieglstein J. Neuroprotective effects of Ginkgo biloba extract. Cell Mol Life Sci 2003; 60: 1779-92.
143. Ponto LL, Schultz SK. Ginkgo biloba extract: Review of CNS effects. Ann Clin Psychiat 2003; 15: 109-19.
144. Christen Y. Ginkgo biloba and neurodegenerative disorders. Front Biosci 2004; 9: 3091-104.
145. Smith JV, Luo Y. Studies on molecular mechanisms of Ginkgo biloba extract. Appl Microbiol Biotechnol 2004; 64: 465-72.
146. Luo Y. Alzheimer’s disease, the nematode Caenorhabditis elegans, and ginkgo biloba leaf extract. Life Sci 2006; 78: 2066-72.
147. Saleem S, Zhuang H, Biswal S, Christen Y, Doré S. Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury. Stroke 2008; 39, 3389-96.
148. Christen Y. Ginkgo biloba and neurodegenerative disorders. Front Biosci. 2004; 1: 3091-104.
149. Bridi R, Crosetti FP, Steffen VM, Henriques AT. The antioxidant activity of standardized extract of Gingko biloba (EGb 761) in rats. Phytother Res 2001; 15: 449-51
150. Colak Ö, Sahin A, Alatas Ö, Inal M, Yasar B, Kiper H. The effect of Ginkgo biloba on the activity of catalase and lipid peroxidation in experimental strangulation ileus. Int J Clin Lab Res 1998; 28: 69-71
151. Sasaki K, Hatta S, Wada K, et al. Effects of extract of Ginkgo biloba leaves and its constituents on carcinogenmetabolizing enzyme activities and glutathione levels in mouse liver. Life Sci 2002; 70: 1657-67
152. Rimbach G, Gohil K, Matsugo S, et al. Induction of glutathione synthesis in human keratinocytes by Ginkgo biloba extract (EGb 761). Biofactors 2001; 15: 39-52.
153. Braquet P. The ginkgolides: Potent platelet-activating factor antagonists isolated from ginkgo biloba L.: Chemistry pharmacology and clinical applications. Drugs Future 1987; 1: 643-88.
154. Braquet P, Hosford D. Ethnopharmacology and the development of natural PAF antagonists as therapeutic agents. J Ethnopharmacol 1991; 32: 135-9.
155. Chan PC, Xia Q, Fu PP. Ginkgo biloba leave extract: Biological medicinal and toxicological effects. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2007; 25: 211-44.
156. Bastianetto S, Ramassamy C, Doré S, Christen S, Poirier J, Quirion R. The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid. Eur J Neurosci 2000; 1: 1882-90.
157. Smith JV, Luo Y. Elevation of oxidative free radicals in Alzheimer’s disease models can be attenuated by Ginkgo biloba extract EGb 761. J Alzheimers Dis 2003; 5: 287-300.
158. Colciaghi F, Borroni B, Zimmermann M, et al. Amyloid precursor protein metabolism is regulated toward alphasecretase pathway by Ginkgo biloba extracts. Neurobiol Dis 2004; 1: 454-60.
159. Stackman RW, Eckenstein F, Frei B, Kulhanek D, Nowlin J, Quinn JF. Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer’s disease by chronic Ginkgo biloba treatment. Exp Neurol 2003; 184: 510-20
160. Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: A review of their intracellular targets. Eur J Pharmacol 2006; 545: 51-64.
161. Maclennan KM, Darlington CL, Smith PF. The CNS effects of Ginkgo biloba extracts and ginkgolide B. Prog Neurobiol 2002 67: 235-57.
162. Kressmann S, Biber A, Wonnemann M, Schug B, Blume HH, Müller WE. Influence of pharmaceutical quality on the bioavailability of active components from Ginkgo biloba preparations. J Pharm Pharmacol 2002; 54: 1507-14.
163. Drago F, Floriddia ML, Cro M, Giuffrida S. Pharmacokinetics and bioavailability of a Ginkgo biloba extract. J Ocul Pharmacol Ther 2002; 18: 197-202.
164. Ude C, Schubert-Zsilavecz M, Wurglics M. Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients. Clin Pharmacokinet 2013; 52: 727-49.
165. Naik SR, Pilgaonkar VW, Panda VS. Evaluation of antioxidant activity of Ginkgo biloba phytosomes in rat brain. Phytother Res 2006; 20: 1013-6.
166. Chen ZP, Sun J, Chen HX, et al. Comparative pharmacokinetics and bioavailability studies of quercetin, kaempferol and isorhamnetin after oral administration of ginkgo biloba extracts, ginkgo biloba extract phospholipid complexes and ginkgo biloba extract solid dispersions in rats. Fitoterapia. 2010; 81: 1045-52.
167. Jin Y, Wen J, Garg S, et al. Development of a novel niosomal system for oral delivery of Ginkgo biloba extract. Int J Nanomed 2013; 8: 421-30.
168. Tang JL, Sun J, He ZG. Self-emulsifying drug delivery systems: strategy for improving oral delivery of poorly soluble drugs. Curr Drug Ther 2007; 2: 85-93.
169. Han L, Fu Y, Cole AJ, Liu J, Wang J. Co-encapsulation and sustained-release of four components in gingko terpenes from injectable PELGE nanoparticles. Fitoterapia 2012; 83: 721-31.
170. Reynolds EH. Mental effects of anticonvulsants, and folic acid metabolism. Brain 1968; 91: 197-214.
171. Botez MI, Reynolds EH, editors. Folic acid in neurology, psychiatry and internal medicine. New York: Raven; 1979.
172. Bottiglieri T, Crellin R, Reynolds EH. Folate and neuropsychiatry. In: Bailey LB, editor. Folate in health and disease. New York: Marcel Dekker 1995; pp: 435-62.
173. Reynolds EH. Benefits and risks of folic acid to the nervous system. J Neurol Neurosurg Psychiatry 2002; 72: 567-71.
174. Reynolds E. Vitamin B12, folic acid, and the nervous system. The Lancet Neurol 2006; 5: 949-60.
175. Kronenberg G, Colla M, Endres M. Folic acid, neurodegenerative and neuropsychiatric sidease. Curr Mol Med 2009; 9: 315-23.
176. Li W, Liu H, Yu M, et al. Folic acid administration inhibits amyloid ß-peptide accumulation in APP/PS1 transgenic mice. J Nutr Biochem 2015; 26: 883-91.
177. Li W, Jiang M, Zhao S, et al. Folic acid inhibits amyloid ß-peptide production through modulating DNA methyltransferase activity in N2a-APP cells. Int J Mol Sci 2015; 16: 25002-13.
178. Wu D, Pardridge WM. Blood-brain barrier transport of reduced folic acid. Pharm Res 1999; 16: 415-9.
179. Kularatne SA, Low PS. Targeting of nanoparticles: folate receptor. Methods Mol Biol. 2010; 624: 249-65.
180. Zheng M, Gong P, Zheng C, et al. Lipid-polymer nanoparticles for folate-receptor targeting delivery of doxorubicin. J Nanosci Nanotechnol 2015; 15: 4792-8.
181. Stella B, Arpicco S, Peracchia MT, et al. Design of folic acidconjugated nanoparticles for drug targeting. J Pharm Sci 2000; 89: 1452-64.
182. Song H, Su C, Cui W, et al. Folic acid-chitosan conjugated nanoparticles for improving tumor-targeted drug delivery. BioMed Research International 2013; http://dx.doi.org/10.1155/2013/723158.
183. Ravouru N, Kondreddy P, Korakanchi D, Haritha M. Formulation and evaluation of niosomal nasal drug delivery system of folic acid for brain targeting. Curr Drug Discov Technol 2013; 10: 270-82.
184. Hussain AA, Dittert LW, Traboulsi A. Brain delivery of folic acid for the prevention of alzheimer’s disease and stroke. US 6369058 B1. 9 April 2002.
185. Etheridge ML, Campbell SA, Erdman AG, Haynes CL, Wolf SM McCullough J. The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine 2013; 9: 1-14.