Olive polyphenols: new promising agents to combat aging-associated neurodegeneration

References

• Rigacci S, Guidotti V, Bucciantini M, et al. Aβ(1-42) aggregates into non-toxic amyloid assemblies in the presence of the natural polyphenol oleuropein aglycon. Curr Alz Res. 2011;8:84152.
   Web of Science ®Google Scholar
• Daccache A, Lion C, Sibille N, et al. Oleuropein and derivatives from olives as Tau aggregation inhibitors. Neurochem Int. 2011;58:700–707.
   PubMed Web of Science ®Google Scholar
• Caruana M, Högen T, Levin J, et al. Inhibition and disaggregation of α-synuclein oligomers by natural polyphenolic compounds. FEBS Lett. 2011;585:1113–1120.
   PubMed Web of Science ®Google Scholar
• Ladiwala AR, Dordick JS, Tessler PM. Aromatic small molecules remodel toxic soluble oligomers of amyloid β through three independent pathways. J Biol Chem. 2011;286:3209–3218.
   PubMed Web of Science ®Google Scholar
• Cheng B, Gong H, Xiao H, et al. Inhibiting toxic aggregation of amyloidogenic proteins: a therapeutic strategy for protein misfolding diseases. Biochim Biophys Acta. 2013;1830:4860–4871.
   PubMed Web of Science ®Google Scholar
• Ahmad E, Ahmad A, Singh S, et al. A mechanistic approach for islet amyloid polypeptide aggregation to develop anti-amyloidogenic agents for type-2 diabetes. Biochimie. 2011;93:793–805.
   PubMed Web of Science ®Google Scholar
• Wu C, Lei H, Wang Z, et al. Phenol red interacts with the protofibril-like oligomers of an amyloidogenic hexapeptide NFGAIL through both hydrophobic and aromatic contacts. Biophys J. 2006;91:3664–3672.
   PubMed Web of Science ®Google Scholar
• Féart C, Samieri C, Allès B, et al. Potential benefits of adherence to the Mediterranean diet on cognitive health. Proc Nutr Soc. 2013;72:140–152.
   PubMed Web of Science ®Google Scholar
• Scarmeas N, Stern Y, Mayeux R, et al. Mediterranean diet and mild cognitive impairment. Arch Neurol. 2009;66:216–225.
   PubMed Web of Science ®Google Scholar
• Pitozzi V, Jacomelli M, Catelan D, et al. Long-term dietary extra-virgin olive oil rich in polyphenols reverses age-related dysfunctions in motor coordination and contextual memory in mice: role of oxidative stress. Rejuvenation Res. 2012;15:601–612.
   PubMed Web of Science ®Google Scholar
• López-Miranda J, Pérez-Jiménez F, Ros E, et al. Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008. Nutr Metab Cardiovasc Dis. 2010;20:284–294.
   PubMed Web of Science ®Google Scholar
• Qosa H, Mohamed LA, Batarseh YS, et al. Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of TgSwDI mice. J Nutr Biochem. 2015;26:1479–1490.
   PubMed Web of Science ®Google Scholar
• Abuznait AH, Qosa H, Busnena BA, et al. Olive-oil-derived oleocanthal enhances βamyloid clearance as a potential neuroprotective mechanism against Alzheimer’s disease: in vitro and in vivo studies. ACS Chem Neurosci. 2013;4:973–982.
   PubMed Web of Science ®Google Scholar
• Grossi C, Rigacci S, Ambrosini S, et al. The polyphenol oleuropein aglycone protects TgCRND8 mice against Aβ plaque pathology. PLoS One. 2013;8:e71762.
   Google Scholar
• Monti MC, Margarucci L, Riccio R, et al. Modulation of tau protein fibrillization by oleocanthal. J Nat Prod. 2012;75:1584–1588.
   PubMed Web of Science ®Google Scholar
• Bach FA, Berry EM, Lairon D, et al. Mediterranean diet pyramid today. Science and cultural updates. Mediterranean diet foundation expert group. Public Health Nutr. 2011;14(12A):2274–2284.
   PubMed Web of Science ®Google Scholar
• Williams RJ, Spencer JP, Rice-Evans C. Flavonoids: antioxidants or signalling molecules?. Free Rad Biol Med. 2004;36:838–849.
   PubMed Web of Science ®Google Scholar
• Halliwell B. Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging. 2001;18:685–716.
   PubMed Web of Science ®Google Scholar
• Stefani M, Rigacci S. Beneficial properties of natural phenols: highlight on protection against pathological conditions associated with amyloid aggregation. BioFactors 2014;40:482–493.
   PubMed Web of Science ®Google Scholar
• Ayissi VB, Ebrahimi A, Schluesenner H. Epigenetic effects of natural polyphenols: a focus on SIRT1-mediated mechanisms. Mol Nutr Food Res. 2014;58:22–32.
   PubMed Web of Science ®Google Scholar
• Vissers MN, Zock PL, Katan MB. Bioavailability and antioxidant effects of olive oil phenols in humans: a review. Eur J Clin Nutr. 2004;58:955–965.
   PubMed Web of Science ®Google Scholar
• Cicerale S, Lucas L, Keast R. Biological activities of phenolic compounds present in virgin olive oil. Int J Mol Sci. 2010;11:458–479.
   PubMed Web of Science ®Google Scholar
• Tripoli E, Giammanco M, Tabacchi G, et al. The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. Nutr Res Rev. 2005;18:98–112.
   PubMed Web of Science ®Google Scholar
• Menotti A, Puddu PE. Coronary heart disease differences across Europe: a contribution from the Seven Countries Study. J Cardiovasc Med (Hagerstown). 2013;14:767–772.
   PubMed Web of Science ®Google Scholar
• Berr C, Portet F, Carriere I, et al. Olive oil and cognition: results from the Three-city study. Dement Geriatr Cogn Disord. 2009;28:357–364.
   PubMed Web of Science ®Google Scholar
• Covas MI. Bioactive effects of olive oil phenolic compounds in humans: reduction of heart disease factors and oxidative damage. Inflammopharmacology. 2008;16:216–218.
   PubMedGoogle Scholar
• Psaltopoulou T, Kosti RI, Haidopoulos D, et al. Olive oil intake is inversely related to cancer prevalence: a systematic review and a meta-analysis of 13,800 patients and 23,340 controls in 19 observational studies. Lipids Health Dis. 2011;10:127.
   PubMed Web of Science ®Google Scholar
• Rigacci S, Stefani M. Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols. Exp Rev Neurother. 2014;15:41–52.
   PubMed Web of Science ®Google Scholar
• Dinda B, Debnath S, Banik R. Naturally occurring iridoids and secoiridoids. An updated review, part 4. Chem Pharm Bull (Tokyo). 2011;59:803–833.
   PubMed Web of Science ®Google Scholar
• Karkoula E, Skantzari A, Melliou E, et al. Direct measurement of oleocanthal and oleacein levels in olive oil by quantitative (1)H NMR. Establishment of a new index for the characterization of extra virgin olive oils. J Agric Food Chem. 2012;60:11696–11703.
   PubMed Web of Science ®Google Scholar
• Fabiani R, Rosignoli P, De Bartolomeo A, et al. Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells. J Nutr. 2008;138:1411–1416.
   PubMed Web of Science ®Google Scholar
• Tundis R, Loizzo M, Menichini F, et al. Biological and pharmacological activities of iridoids: recent developments. Mini Rev Med Chem. 2008;8:399–420.
   PubMed Web of Science ®Google Scholar
• Ranalli A, Marchegiani D, Contento S, et al. Variations of iridoid oleuropein in Italian olive varieties during growth and maturation. Eur J Lipid Sci Technol. 2009;111:678–687.
   Web of Science ®Google Scholar
• Servili M, Montedoro GF. Contribution of phenolic compounds in virgin olive oil quality. Eur J Lipid Sci Technol. 2002;104:602–613.
   Web of Science ®Google Scholar
• Selkoe DJ. Folding proteins in fatal ways. Nature. 2003;426:900–904.
   PubMed Web of Science ®Google Scholar
• Stefani M. Structural features and cytotoxicity of amyloid oligomers: implications in Alzheimer’s disease and other diseases with amyloid deposits. Progress Neurobiol. 2012;99:226–245.
   PubMed Web of Science ®Google Scholar
• Rigacci S, Guidotti V, Bucciantini M, et al. Oleuropein aglycon prevents cytotoxic amyloid aggregation of human amylin. J Nutr Biochem. 2010;21:726–735.
   PubMed Web of Science ®Google Scholar
• Leri M, Nosi D, Natalello A, et al. The polyphenol Oleuropein aglycone hinders the growth of toxic transthyretin amyloid assemblies. J Nutr Biochem. 2016;30:153–166.
   PubMed Web of Science ®Google Scholar
• Pitt J, Roth W, Lacor P, et al. Alzheimer’s-associated Aβ oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal. Toxicol Appl Pharmacol. 2009;240:189–197.
   PubMed Web of Science ®Google Scholar
• Galanakis PA, Bazoti FN, Bergquist J, et al. Study of the interaction between the amyloid beta peptide (1-40) and antioxidant compounds by nuclear magnetic resonance spectroscopy. Biopolymers. 2011;96:316–327.
   PubMed Web of Science ®Google Scholar
• Ladiwala AR, Mora-Pale M, Lin JC, et al. Polyphenolic glycosides and aglycones utilize opposing pathways to selectively remodel and inactivate toxic oligomers of amyloid β. ChemBioChem. 2011;12:1749–1758.
   PubMed Web of Science ®Google Scholar
• Kostomoiri M, Fragkouli A, Sagnou M, et al. Oleuropein, an anti-oxidant polyphenol constituent of olive promotes α-secretase cleavage of the amyloid precursor protein (AβPP). Cell Mol Neurobiol. 2013;33:147–154.
   PubMed Web of Science ®Google Scholar
• Monti MC, Margarucci L, Tosco A, et al. New insights on the interaction mechanism between tau protein and oleocanthal, an extra-virgin olive-oil bioactive component. Food Funct. 2011;2:423–428.
   PubMed Web of Science ®Google Scholar
• Cassiano C, Casapullo A, Tosco A, et al. In cell interactome of oleocanthal, an extra virgin olive oil bioactive component. Nat Prod Commun. 2015;10:1013–1016.
   PubMed Web of Science ®Google Scholar
• Margarucci L, Monti MC, Cassiano C, et al. Chemical proteomics-driven discovery of oleocanthal as an Hsp90 inhibitor. Chem Commun (Camb). 2013;49:5844–5846.
   PubMed Web of Science ®Google Scholar
• Rigacci S. Olive oil phenols as promising multi-targeting agents against Alzheimer’s disease. Adv Exp Med Biol. 2015;863:1–20.
   PubMed Web of Science ®Google Scholar
• De Bock M, Derraik JGB, Brennan CM, et al. Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial. PLoS One. 2013;8:e57622.
   PubMed Web of Science ®Google Scholar
• Wainstein J, Ganz T, Boaz M, et al. Olive leaf extract as a hypoglycemic agent in both human diabetic subjects and in rats. J Med Food. 2012;15:605–610.
   PubMed Web of Science ®Google Scholar
• Biessels GJ, Reagan LP. Hippocampal insulin resistance and cognitive dysfunction. NatureRev Neurol. 2015;16:660–671.
   Web of Science ®Google Scholar
• Bitra VR, Deepthi Rapaka D, Akula A. Prediabetes and Alzheimer’s Disease. Indian J Pharm Sci. 2015;77:511–514.
   PubMed Web of Science ®Google Scholar
• Bedse G, Di Domenico F, Serviddio G, et al. Aberrant insulin signaling in Alzheimer’s disease: current knowledge. Front Neurosci. 2015;9:204.
   PubMed Web of Science ®Google Scholar
• De La Monte SM. Type 3 diabetes in sporadic Alzheimer׳s disease: mini-review. Eur Neuropsychopharmacol. 2014;24:1954–1960.
   PubMed Web of Science ®Google Scholar
• Jolivalt CG, Lee CA, Beiswenger KK, et al. Defective insulin signaling pathway and increased glycogen synthase kinase-3 activity in the brain of diabetic mice: parallels with Alzheimer’s disease and correction by insulin. J Neurosci Res. 2008;86:3265–3274.
   PubMed Web of Science ®Google Scholar
• Rigacci S, Stefani M. Nutraceutical properties of olive oil polyphenols. An itinerary from cultured cells through animal models to humans. Int J Mol Sci. 2016;17:pii:E843.
   PubMed Web of Science ®Google Scholar
• Xu J, Kao S-Y, Lee FJS, et al. Dopamine-dependent neurotoxicity of α-synuclein: a mechanism for selective neurodegeneration in Parkinson’s’s disease. Nat Med. 2002;8:600–606.
   PubMed Web of Science ®Google Scholar
• Burke WJ, Li SW, Williams EA, et al. 3,4-Dihydroxyphenylacetaldehyde is the toxic dopamine metabolite in vivo: implications for Parkinson’s’s disease pathogenesis. Brain Res. 2003;989:205–213.
   PubMed Web of Science ®Google Scholar
• Schaffer S, Podstawa M, Visioli F, et al. Hydroxytyrosol-rich olive mill wastewater extract protects brain cells in vitro and ex vivo. J Agr Food Chem. 2007;55:5043–5049.
   PubMed Web of Science ®Google Scholar
• González-Correa JA, Navas MD, Lopez-Villodres JA, et al. Neuroprotective effect of hydroxytyrosol and hydroxytyrosol acetate in rat brain slices subjected to hypoxia-reoxygenation. Neurosci Lett. 2008;446:143–146.
   PubMed Web of Science ®Google Scholar
• Sarsour EH, Kumar MG, Kalen AL, et al. MnSOD activity regulates hydroxytyrosolinduced extension of chronological lifespan. Age (Dordr). 2012;34:95–109.
   PubMed Web of Science ®Google Scholar
• Canuelo A, Gilbert-Lopez B, Pacheco-Linan P, et al. Tyrosol, a main phenol present in extra virgin olive oil, increases lifespan and stress resistance in Caenorhabditis elegans. Mech Ageing Dev. 2012;133:563–574.
   PubMed Web of Science ®Google Scholar
• Odiatou EM, Skaltsounis AL, Constantinou A. Identification of the factors responsible for the in vivo pro-oxidant and cytotoxic activities of the olive polyphenols oleuropein and hydroxytyrosol. Cancer Lett. 2013;330:113–121.
   PubMed Web of Science ®Google Scholar
• Menendez JA, Joven J, Aragonès G, et al. Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil: A new family of gerosuppressant agents. Cell Cycle. 2013;12:555–578.
   PubMed Web of Science ®Google Scholar
• Rigacci S, Miceli C, Nediani C, et al. Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: a mechanistic insight. Oncotarget. 2015;6:35344–35357.
   PubMed Web of Science ®Google Scholar
• Wang M, Yu T, Zhu C, et al. Resveratrol triggers protective autophagy through the Ceramide/Akt/mTOR pathway in melanoma B16 cells. Nutr Cancer. 2014;66:435–440.
   PubMed Web of Science ®Google Scholar
• St-Laurent-Thibault C, Arseneault M, Longpre F, et al. Tyrosol and hydroxytyrosol two main components of olive oil, Protect N2a cells against amyloid-β-induced toxicity. Involvement of the NF-κB signaling. Curr Alz Res. 2011;8:543–551.
   PubMed Web of Science ®Google Scholar
• Yu G, Deng A, Tang W, et al. Hydroxytyrosol induces phase II detoxifying enzyme expression and effectively protects dopaminergic cells against dopamine- and 6-hydroxydopamine induced cytotoxicity. Neurochem Int. 2016;96:113–120.
   PubMed Web of Science ®Google Scholar
• Galinano V, Villalain J. Oleuropein aglycone in lipid bilayer membranes. A molecular dynamics study. Biochim Biophys Acta. 2015;1848:2849–2858.
   PubMed Web of Science ®Google Scholar
• Peyrot Des Gachons C, Uchida K, Bryant B, et al. Unusual pungency from extra virgin olive oil is attributable to restricted spatial expression of the receptor of oleocanthal. J Neurosci. 2011;31:999–1009.
   PubMed Web of Science ®Google Scholar
• Diomede L, Rigacci S, Romeo M, et al. Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit. PLoS One. 2013;8:e58893.
   PubMed Web of Science ®Google Scholar
• Chishti MA, Yang DS, Janus C, et al. Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem. 2001;276:21562–21570.
   PubMed Web of Science ®Google Scholar
• Luccarini I, Grossi C, Rigacci S, et al. Oleuropein aglycone protects against pyroglutamylated-3 amyloid-β toxicity: biochemical, epigenetic and functional correlates. Neurobiol Aging. 2015;36:648–663.
   PubMed Web of Science ®Google Scholar
• Pantano D, Luccarini I, Nardiello P, et al. Oleuropein aglycone and polyphenols from olive mill wastewater ameliorate cognitive deficits and neuropathology. Br J Clin Pharmacol. 2016. Published on line 2016 Aug 18. DOI:10.1111/bcp.12993
   PubMedGoogle Scholar
• Luccarini I, Ed Dami T, Grossi C, et al. Oleuropein aglycone counteracts Aβ42 toxicity in the rat brain. Neurosci Lett. 2014;558:67–72.65.
   PubMed Web of Science ®Google Scholar
• Qosa H, Batarseh YS, Moyeldin MM, et al. Oleocanthal enhances amyloid-β clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model. ACS Chem Neurosci. 2015;6:1849–1859.
   PubMed Web of Science ®Google Scholar
• Arunsundar M, Shanmugarajan TS, Ravichandran V. 3,4-dihydroxyphenylethanol attenuates spatio-cognitive deficits in an Alzheimer’s disease mouse model: modulation of the molecular signals in neuronal survival-apoptotic programs. Neurotox Res. 2015;27:143–155.
   PubMed Web of Science ®Google Scholar
• Remely M, Stefanska B, Lovrecic L, et al. Nutriepigenomics: the role of nutrition in epigenetic control of human diseases. Curr Opin Clin Nutr Metab Care. 2015;18:328–333.
   PubMed Web of Science ®Google Scholar
• Gräff J, Rei D, Guan JS, et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature. 2012;483:222–226.
   PubMed Web of Science ®Google Scholar
• Adwan L, Zawia NH. Epigenetics: a novel therapeutic approach for the treatment ofAlzheimer’s disease. Pharmacol Ther. 2013;139:41–50.
   PubMed Web of Science ®Google Scholar
• Covas MI, Konstantinidou V, Fitó M. Olive oil and cardiovascular health. J Cardiovasc Pharmacol. 2009;54:477–482.
   PubMed Web of Science ®Google Scholar
• Martínez-Lapiscina EH, Clavero P, Toledo E, et al. Virgin olive oil supplementation and long-term cognition: theMediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Nutr Health Aging. 2013;17:544–552.
   PubMed Web of Science ®Google Scholar
• Valls-Pedret C, Lamuela-Raventos RM, Medina-Remon A, et al. Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alz Dis. 2012;29:773–782.
   PubMed Web of Science ®Google Scholar
• Knight A, Bryan J, Wilson C, et al. A randomised controlled intervention trial evaluating the efficacy of a Mediterranean dietary pattern on cognitive function and psychological wellbeing in healthy older adults: the MedLey study. BMC Geriatr. 2015;15:55.
   PubMed Web of Science ®Google Scholar
• Valls-Pedret C, Sala-Vila A, Serra-Mir M, et al. Mediterranean diet and age-related cognitive decline: a randomized clinical trial. JAMA Intern Med. 2015;175:1094–1103.
   PubMed Web of Science ®Google Scholar
• Martínez-Lapiscina EH, Galbete C, Corella D, et al. Genotype patterns at CLU, CR1, PICALM and APOE, cognition and Mediterranean diet: the PREDIMED-NAVARRA trial. Genes Nutr. 2014;9:393.
   PubMed Web of Science ®Google Scholar
• Nemeth K, Plumb GW, Berrin JG, et al. Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr. 2002;42:29–42.
   Web of Science ®Google Scholar
• Sang S, Lambert JD, Ho CT, et al. The chemistry and biotransformation of tea constituents. Pharmacol Res. 2011;64:87–99.
   PubMed Web of Science ®Google Scholar
• Wu B, Kulkarmi K, Basu S, et al. First-pass metabolism via UDP-glucuronyltransferase: a barrier to oral bioavailability of phenolics. J Pharm Sci. 2011;100:3655–3681.
   PubMed Web of Science ®Google Scholar
• Manach C, Scalbert A, Morand C, et al. Dietary polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79:727–747.
   PubMed Web of Science ®Google Scholar
• Ozdal T, Sela DA, Xiao J, et al. The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility. Nutrients. 2016;8:pii: E78.
   PubMed Web of Science ®Google Scholar
• Dueñas M, Cueva C, Muñoz-González I, et al. Studies on modulation of gut microbiota by wine polyphenols: from isolated cultures to Omic approaches. Antioxidants (Basel). 2015;4:1–21.
   PubMedGoogle Scholar
• Etxeberria U, Arias N, Boqué N, et al. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. J Nutr Biochem. 2015;26:651–660.
   PubMed Web of Science ®Google Scholar
• Dueñas M, Muñoz-González I, Cueva C, et al. A survey of modulation of gut microbiota by dietary polyphenols. Biomed Res Int. 2015;2015:850902.
   PubMed Web of Science ®Google Scholar
• Moreno-Indias I, Sánchez-Alcoholado L, Pérez-Martínez P, et al. Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients. Food Funct. 2016;7:1775–1787.
   PubMed Web of Science ®Google Scholar
• Roopchand DE, Carmody RN, Kuhn P, et al. Dietary polyphenols promote growth of the gut bacterium akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes. 2015;64:2847–2858.
   PubMed Web of Science ®Google Scholar
• Gasperotti M, Passamonti S, Tramer F, et al. Fate of microbial metabolites of dietary polyphenols in rats: is the brain their target destination?. ACS Chem Neurosci. 2015;6:1341–1352.
   PubMed Web of Science ®Google Scholar
• Wang D, Ho L, Faith J, et al. Role of intestinal microbiota in the generation of polyphenolderived phenolic acid mediated attenuation of Alzheimer’s disease β-amyloid oligomerization. Mol Nutr Food Res. 2015;59:1025–1040.
   PubMed Web of Science ®Google Scholar
• Lin P, Qian W, Wang X, et al. The biotransformation of oleuropein in rats. Biomed Chromatogr. 2013;27:1162–1167.
   PubMed Web of Science ®Google Scholar
• Corona G, Tzounis X, Dessì MA, et al. The fate of olive oil polyphenols in the gastrointestinal tract. Implications of gastric and colonic microflora-dependent biotransformation. Free Rad Res. 2006;40:647–658.
   PubMed Web of Science ®Google Scholar
• Martín-Peláez S, Mosele JI, Pizarro N, et al. Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: implications of human gut microbiota. Eur J Nutr. 2015. Published online 2016 Nov 5. DOI:10.1007/s00394-015-1063-2
   Google Scholar
• Mosele JI, Martín-Peláez S, Macià A, et al. Faecal microbial metabolism of olive oil phenolic compounds: in vitro and in vivo approaches. Mol Nutr Food Res. 2014;58:1809–1819.
   PubMed Web of Science ®Google Scholar
• Markopoulos C, Vertzoni M, Agalias A, et al. Stability of oleuropein in the human proximal gut. Pharm Pharmacol. 2009;61:143–149.
   PubMed Web of Science ®Google Scholar
• Bazoti FN, Gikas E, Tsarbopoulos A. Simultaneous quantification of oleuropein and its metabolites in rat plasma by liquid chromatography electrospray ionization tandem mass spectrometry. Biomed Chrom. 2010;24:506–515.
   PubMed Web of Science ®Google Scholar
• Vissers MN, Zock PL, Roodenburg AJC, et al. Olive oil phenols are absorbed in humans. J Nutr. 2002;132:409–417.
   PubMed Web of Science ®Google Scholar
• De Bock M, Thorstensen EB, Derraik JGB, et al. Human absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract. Mol Nutr Food Res. 2013;57:2079–2085.
   PubMed Web of Science ®Google Scholar
• Garcia-Villalba R, Larrosa M, Possemiers S, et al. Bioavailability of phenolics from an oleuropein-rich olive (Olea europaea) leaf extract and its acute effect on plasma antioxidant status: comparison between pre- and postmenopausal women. Eur J Nutr. 2014;53:1015–1027.
   PubMed Web of Science ®Google Scholar
• Serra A, Rubiò L, Borràs X, et al. Distribution of olive oil phenolic compounds in rat tissues after administration of a phenolic extract from olive cake. Mol Nutr Food Res. 2012;56:486–496.
   PubMed Web of Science ®Google Scholar
• Quirantes-Piné R, Zurek G, Barrajòn-Catalàn E, et al. A metabolite-profiling approach to assess the uptake and metabolism of phenolic compounds from olive leaves in SKBR3 cells by HPLC-ESI-QTOF-MS. J Pharm Biomed Anal. 2013;72:121–126.
   PubMed Web of Science ®Google Scholar
• Turner RS, Thomas RG, Craft S, et al. Alzheimer’s Disease Cooperative Study. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015;85:1383–1391.
   PubMed Web of Science ®Google Scholar
• Ringman JM, Frautschy SA, Teng E, et al. Oral curcumin for Alzheimer’s disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther. 2012;4:43.
   PubMed Web of Science ®Google Scholar
• Cheng KK, Yeung CF, Ho SW, et al. Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer’s disease Tg2576 mice. The AAPS J. 2013;15:324–336.
   PubMed Web of Science ®Google Scholar