Month: February 2019

Epigenetics, environmental responses and viticulture

By Anabella Varela, Federico Berli, Carlos Marfil and Verónica Noé Ibañez

Since plants as sessile organism cannot escape from stressful environmental conditions they have developed morphophysiological and biochemical adjustments (phenotypes), as the result of short-term gene expression changes (Atkinson and Urwin, 2012) and epigenetic modifications like DNA methylation (Jablonka and Raz, 2009). The ability of an organism to express diverse phenotypes in different environments is called phenotypic plasticity. This plasticity is part of acclimation processes, which prevent plants from dying and enable plant production in diverse environments. Grapevine possess high phenotypic plasticity allowing it to grow in very contrasting environments around the world.
Epigenetic modifications refer to heritable and reversible changes in gene expression (which afterwards may lead to changes in the phenotype) without changes in the DNA sequence. This definition has two important concepts. First, that heritable changes in gene expression may play a role in phenotypic plasticity (Zhang et al., 2013) which in line to what we said above, increase the acclimation of plants to various abiotic and biotic factors (Johannes et al., 2009). Secondly, since these modifications happens without changes in the DNA sequence, two grapevines clones originated from the same mother can still present phenotypic differences. The late concept takes special relevance from an oenological point of view, since berry and wine composition (quality) can be associated with a wine region or specific vineyard, concept known as terroir that involves plant material (genotype), environmental conditions and management characteristics (Van Leeuwen et al., 2004).


We present some important findings recently published by our research group from the Instituto de Biología Agrícola de Mendoza, CONICET-Universidad Nacional de Cuyo, Argentina, in collaboration with the Catena Institute of Wine, Bodega Catena Zapata. The paper by Marfil et al. (2019) evaluates whether different environmental signals induce DNA methylation changes in the Malbec genome, the emblematic variety of Argentine viticulture. Also, correlate this epigenetic mechanism with the variability observed in sensory quality compounds such as polyphenols, and study to what extent this epigenetic characteristic is inherited as part of an acclimation mechanism.
The experiment was conducted during two growing seasons in field grown Vitis vinifera L. cv. Malbec plants exposed to contrasting ultraviolet-B radiation (UV-B; minus UV-B vs. high UV-B) and water regimes (well-watered vs. water deficit). These environmental signals were chosen because are common in our local environmental conditions. Mendoza is the main wine region of Argentina, having high-altitude vineyards reaching up to 1400 m a.s.l. These vineyards cultivated with elevated UV-B levels are drip irrigated and produce deep and colorful red wines. Both components are considered within the terroir concept, i.e. UV-B, as an abiotic factor, and water restriction, as both an abiotic factor and a management practice.


High UV-B and water deficit were the treatments that induced greater number of DNA methylation changes respect to Control (minus UV-B and well-watered). In addition, high UV-B was associated with flavonols accumulation, suggesting that DNA methylation could regulate sensory quality compounds accumulation and participate in acclimation mechanisms.


  • Solar ultraviolet-B radiation (UV-B) and water deficit induce grapevine DNA methylation changes
  • UV-B is associated with flavonols accumulation in berries and early fruit shoots
  • Flavonol response to UV-B can be DNA methylation dependent and inherited

Those interested in a longer length report can download the working paper at:



Anabella Varela

Masters degree in Vititulture and Oenology in the University of Padova, Udine and Verona. PhD student working on Vitis vinifera epigenetics in the Instituto de Biología Agrícola de Mendoza, CONICET-Universidad Nacional de Cuyo, Argentina. Advisors: Carlos Marfil and Federico Berli.


Federico Berli

Professor of Plant Biochemistry and Researcher in the Instituto de Biología Agrícola de Mendoza, CONICET-Universidad Nacional de Cuyo, Argentina. His research is focused on the effects of environmental factors on the grapevine physiology. He is author of 21 papers in international scientific journals. Mail:


Carlos Marfil

Professor of Genetics and Researcher in the Instituto de Biología Agrícola de Mendoza, CONICET-Universidad Nacional de Cuyo, Argentina. We develop researches related to the study of epigenetic variability as a source of phenotypic novelties in plants: we are interested in describing factors that generate epigenetic variability and the stability and importance of this variability in processes of acclimatization, adaptation and plant diversification. To study the environmental induced epigenetic variation we use as experimental models germplasm from agro-ecosystems (vine) and from natural ecosystems (wild potato species).


Verónica Noé Ibañez

Agricultural engineer, from the National University of Cuyo. PhD student in the Instituto de Biología Agrícola de Mendoza, CONICET-Universidad Nacional de Cuyo, Argentina. Her research is focused on environmental induced epigenetic variation under natural conditions in Solanum kurtzianum, the argentine wild potato best adapted to desert regions. Advisors: Carlos Marfil.



Atkinson, N.J., Urwin, P.E., 2012. The interaction of plant biotic and abiotic stresses: from genes to the field. J. Exp. Bot. 63, 3523–3544.

Jablonka, E.V.A., Raz, G.A.L., 2009. Transgenerational epigenetic inheritance: pre- valence, mechanisms, and implications for the study of heredity and evolution. Q. Rev. Biol. 84, 131–176.

Johannes, F., Porcher, E., Teixeira, F.K., Saliba-Colombani, V., Simon, M., Agier, N., Bulski, A., Albuisson, J., Heredia, F., Audigier, P., 2009. Assessing the impact of transgenerational epigenetic variation on complex traits. PLoS Genet. 5 e1000530- e1000530.

Marfil C., Ibañez V., Alonso R., Varela A., Bottini R., Masuelli R., Fontana A., Berli F., 2018. Changes in grapevine DNA methylation and polyphenols content induced by solar ultraviolet-B radiation, water deficit and abscisic acid spray treatments. Plant Physiol. Biochem. 135, 287–294.

Van Leeuwen, C., Friant, P., Choné, X., Tregoat, O., Koundouras, S., Dubourdieu, D., 2004. Influence of climate, soil, and cultivar on terroir. Am. J. Enol. Vitic. 55, 207–217.

Zhang, Y.Y., Fischer, M., Colot, V., Bossdorf, O., 2013. Epigenetic variation creates po- tential for evolution of plant phenotypic plasticity. New Phytol. 197, 314–322.


Posted by in Viticulture

Application of ozone during grape drying to produce straw wine. Effects on the microbiota and compositive profile of grapes.

By Raffaele Guzzon

Ozone is an emerging tool in winemaking, recently applied for controlling spoilage microorganisms in winery. This sanitizer has some attractive features. Thanks to a new generation of O3 generator is possible a cheap and in situ production of this gas. Ozone counteract the development of a large range of microorganism, from viruses to molds. Also, it is able to eliminate the parasites of the fresh fruits such as insects that can be vectors of dangerous microbial contaminations (i.e. the sour rot due to D. suzukii proliferation). The high reactivity of ozone ensures it disappearance already after few minutes from the application, therefore this gas is particularly interesting in the treatment of food because the risk of residues that can affect the safety of consumers are totally excluded. For these reasons the ozone finds numerous applications in the post-harvest treatment of vegetable and fruits, to preserve they from microbial spoilage. The study recently published on the Journal of Applied Microbiology from Raffaele Guzzon and her colleagues of the Edmund Mach Foundation (Italy) describes a new application of ozone as effective and safe alternative to chemical preservatives which are today involved in the control of microbial alterations of grapes.
The Italian’s researchers applied the ozone at the conservation of grapes involved in the production of straw wines. The production of sweet wine from dried grapes is an ancient technology, widespread in the Mediterranean area. In this winemaking process, grapes were dried before crushing for a long period, to concentrate their components and enhance their biotransformation, which results in peculiar flavors and taste of the final wines. Some straw wines are present in Italy (Amarone della Valpolicella, Vino Santo Trentino, Vin Santo Toscano, Passito di Pantelleria), Spain (Sherry), Greece (Samos’s wines), in all of these must made from dried grapes contains high concentration of fermentable sugars, which does not fit with the technological potentiality of oenological yeasts. Indeed, the alcoholic fermentation stops after the production of about 13 - 15% v/v ethanol, and a relevant amount of sugars resides stably in wine.

On the contrary, grapes are not microbiologically stable during the drying period that follows harvesting. Bunches are stored in fresh and ventilated warehouses to allow a gentle water loss. This process usually takes usually between 3 and 6 months, and exposes grapes to the risk of microbial spoilage, product losses, and accumulation of toxic compounds such as ochratoxin A. In this work the ozone was evaluated as tool to preserve grapes during drying, in terms of qualitative and quantitative changes induced in the epiphytic microflora. In addition, the alteration exerted by ozone on grape’s chemical composition was analyzed. This latter deepening is necessary because ozone is a powerful oxidizing agent and one must be sure that it does not alter the organoleptic profile of the wines derived from the grapes exposed to it. Grapes from four vine varieties were treated with ozone produced by a cold plasma generator during the entire drying period (6 weeks). Treatments with ozone were performed weekly and each of them lasted 6 hours, reaching an O3 concentration of about 100 ppm. The microflora was quantified 12 hours after O3 treatments by plate count and characterized by 454-pyrosequencing. Obtained results were compared with those obtained on identical, untreated, grape samples. At the end of drying, an extensive chemical characterization was performed onto the whole mass of grapes by FT-IR and GC-MS.


Figure. Evolution of the microflora during 6 weeks of grape drying in function of ozone treatments. A. Total yeast population. B Non-Saccharomyces yeast. C. Acetic bacteria. D. Lactic acid bacteria (mean ± SD; n=5). Riesling; ◊ Riesling O3; ▴ Gewurztraminer; ▵ Gewurztraminer O3; ▪ Sauvignon; ▫Sauvignon O3; ● Moscato; ○ Moscato O3.

The experiments demonstrated that ozone acts as antiseptic agents maintaining the microflora of treated grapes under the limit of spoilage activity, in particular for Botrytis cinerea and acetic acid bacteria. The 454-pyrosequencing of grapes at the end of drying showed two different microbiota profiles, in function of the treatment performed on grapes. In the case of ozone treated grapes, we observed maintenance of a large biodiversity, with the prevalence of yeasts involved in the first steps of winemaking process. In untreated grape samples we observed the opposite situation, and Acetobacter sp. and Botrytis sp. dominated the microbiota. The GC-MS characterization of volatile profile of dried grapes excluded alteration due to ozone that do not negatively affect the studied free and bound volatile compounds. No significant differences were observed in terms of volatile compounds typical of the studied aromatic grape varieties, which therefore are suitable for the production of high-quality wines.


These promising results must be considered as preliminary evidences, and some of the observed differences between control and ozone-treated samples need further confirmation with a larger experimental plan. Nevertheless, this study already highlights that ozone treatment of grapes could be a promising solution to improve the conservation of wine grapes after harvesting.
Those interested in a longer length report can download the working paper at:


Raffaele Guzzon

After graduating in Food Technology at the University of Parma (Italy), he earned the PhD at the University of Trento, with a work about the application of immobilized microbial cultures of lactic bacteria at the oenological fermentation. He works since 2003 at the Edmund Mach Foundation, a research center based in the North of Italy, and currently he coordinates the local food microbiological laboratory. Raffaele Guzzon teaches Wine Microbiology at the Course of Viticulture and Enology of the University of Trento. He performs consulting in the fields of microbiology and winemaking in some Italian wineries.
The main fields of scientific activities concern the study of evolution of microbial ecosystems during the winemaking and the impact of oenological practices on them. He carries out experiments to optimize the winemaking protocols by the use of environmentally-friendly technologies. Winner in 2009 of the Award of the Italian Society of Viticulture and Enology "Italian Research for Development", was a finalist in all subsequent editions. He is the author of numerous publications on scientific and technical journals.

Posted by in Viticulture

New insights about the functionalities of oenological tannins

By Adeline Vignault, Jordi Gombau,Joan Miquel Canals, Pierre-Louis Teissedre and Fernando Zamora

The use of oenological tannins in winemaking is a common practice but the International Organization of Vine and Wine (OIV) only authorize nowadays their use for wine fining [1]. Nevertheless, it is incontestable that oenological tannins are also currently used for many other purposes. Indeed, the literature has attributed several other functionalities to oenological tannins, such as antioxidant activity [2], direct consumption of dissolved oxygen [2,3], antioxidasic activity [4], ability to scavenge peroxyl radicals [5], ability to chelate iron (II), prevention of oxidative damage mediated by Fenton-based reactions [6], color improvement and stabilization of red wines [7], direct formation of new pigments [8], improvement of wine structure and mouthfeel [9], copigmentation effect [10], elimination of reduction odors [9] and even bacteriostatic effects [11].
Although oenological tannins are commonly employed to these ends, there are many questions about them that need to be clarified because many of these functionalities have only been verified empirically and there is a lack of scientific literature showing that oenological tannins really exert these functions. Moreover, under the term oenological tannin is included a wide range of phenolic compounds which differ in chemical structure, botanical origin, manufacturing process and probably in their effectiveness for the different described functionalities. This broad family of substances includes hydrolysable tannins (gallotannins and ellagitannins) from nut galls, tara, oak and chestnut, and condensed tannins (proanthocyanidins) from grape seeds and skins and other plant sources, such as quebracho, mimosa and acacia [8].

For that reason, the OIV working group on oenological tannins has performed an exhaustive study with 36 oenological commercial tannins to determine their chemical composition and verify their possible functionalities in order to include it in the OIV International Oenological Codex. Specifically this study has analyzed the functionalities of 17 proanthocyanidins comprising 9 procyanidins/prodelphinidins (PC/PD: 3 from grapes, 4 from grape seeds and 2 from grape skin) and 8 profisetinidins/prorobinetidins (PF/PR: 2 from acacia and 6 from quebracho), and 19 hydrolysable tannins comprising 8 gallotannins (GT: 4 from nut galls and 4 from tara) and 11 ellagitannins (ET: 8 from oak and 3 from chestnut). This post synthetize some of the main results obtained up to the current date. Specifically this post is focused in their chemical composition (Total Polyphenol Index [12], Bate-Smith [13], Methyl-cellulose [14], Folin-Ciocalteu [15], OIV official method [2] and phloroglucinolisis [16]), the antioxidant capacities (ABTS, CUPRAC, DPPH, FRAP and ORAC methods) [2], the direct oxygen consumption rate [2,3], the inhibitory effect on laccase activity [17] and the effectiveness as copigments to improve the color of red wines [10]. Some of these results have been previously published [2,3,10,18].
Figure 1 shows the principal component analysis corresponding to the chemical composition of the thirty-six different commercial tannins. This PCA enabled the different oenological tannins to be separated with only two incorrect classifications. More specifically, PC1 placed ET on the left and PC/PD on the right, with GT and PF/PR being in the center. PC2 enabled GT and PF/PR to be separated, locating GT above PF/PR.

Figure 2 shows the principal component analysis corresponding to the antioxidant capacities of the 36 different commercial tannins. In that case, PCA enable to distinguish between hydrolysable and condensed tannins according to their antioxidant capacities, but cannot differentiate between PC/PD and PF/PR or between GT and ET. These data also indicates that hydrolysable tannins have higher antioxidant activity than condensed tannins.

Figure 3 shows the oxygen consumption rate (OCR) of the different types of commercial tannins. This data confirms that ellagitannins are the most effective of the various oenological tannins, followed in decreasing order by condensed tannins (PC/PD and PF/PR) and finally gallotannins in terms of protecting the wine against chemical oxidation.

Figure 4 shows the inhibitory effect of the different types of commercial tannins on the laccase activity. All the tannins exerted an inhibitory effect on laccase activity which depended of the tannin dose. Indeed, the higher is the dose used lower is the laccase residual activity. This data confirms the utility of using oenological tannins to protect grape juice and wine from browning when grey root is present in the grapes.

Figure 5 shows the effectiveness of the different type of commercial tannins as copigments in a wine model solution containing 50 mg/L of malvidin-3-O-glucoside. The results indicate that the presence of (-)-epicatechin and all the types of commercial tannins increase red color (A520nm) of the solution and that this increase is greater when the copigment/pigment ratio is higher. This data confirms therefore that all of them are good copigments and consequently it can be asserted that supplementation with commercial tannins exert a beneficial effect on the color of red wines

It can be concluded that oenological tannins really exert a protection effect against wine oxidation because they have antioxidant activity, they consume directly oxygen and they exert an inhibitory effect on the laccase activity. Moreover, oenological tannins also exert a copigmentation effect which can improve and protect de color of red wines. Further studies are required to deep in the knowledge of the functionalities of oenological tannins but the actual findings suggest the need to include these new functionalities of oenological tannins in the OIV International Oenological Codex.

1 Université de Bordeaux, Unité de recherche Œnologie, EA 4577, USC 1366 INRA, ISVV, 33882 Villenave d’Ornon cedex, France.
2 Departament de Bioquímica i Biotecnologia, Facultat d’Enologia de Tarragona, Universitat Rovira i Virgili, C/ Domingo 1, 43007 Tarragona, Spain

Research Groups:
Adeline Vignault and Pierre-Louis Teissedre. Université de Bordeaux, Unité de recherche Œnologie
Jordi Gombau, Joan Miquel Canals and Fernando Zamora. Universidad Rovira i Virgili. Group of Research in Oenological Technology
Both research groups focus mainly their studies on the role of phenolic compounds on the color, astringency and general quality of red wines. Recently, they have begun a collaboration with the aim of studying the chemical characterization and functionalities of oenological tannins within the framework of the working group on oenological tannins of the International Organization of Vine and Wine (OIV).


  1. International Oenological Codex. COEI-1-TANINS: 2015.
  2. Vignault, M.R. González-Centeno, O. Pascual, J. Gombau, M. Jourdes, V. Moine, N. Iturmendi, J.M. Canals, F. Zamora, P.L. Teissedre, Food Chem. 268, 210-219 (2018)
  3. Pascual, A. Vignault, J. Gombau , M. Navarro, S. Gómez-Alonso, E. García-Romero, J.M. Canals, I. Hermosín-Gutíerrez, P.L. Teissedre, F. Zamora, Food Chemistry, 234, 26-32 (2017)
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  12. Ribéreau-Gayon, D. Dubourdieu, B. Donèche, (2006). Handbook of enology (2nd ed.). Chichester, West Sussex, England; Hoboken, NJ: John Wiley.
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Posted by in Viticulture

The beneficial effects of wine polyphenols on Alzheimer’s disease

By Paula Silva

With aging decline of cognitive function occurs, but the mechanisms responsible are unknown. However, is now acknowledged that several lifestyle factors (e.g. diet, cognitive and physical activities) have an impact on brain aging and the development of neurodegenerative diseases. This post is about the neuroprotective abilities of the wine polyphenols (Figure 1) in correlation to the pathophysiological mechanisms involved in Alzheimer's disease (AD) and summarizes a part of a recent review paper written by me in collaboration with David Vauzour published in Beverages Journal [1].

Figure 1. Red and white wine phenolic composition.

Alzheimer’s disease is the most common form of dementia and its prevalence increases with age. The pathological hallmark of AD is the extracellular deposition of amyloid-β aggregates which is the main component of senile plaques contributing to neuronal dysfunction and behavioural changes. Mechanisms that underlie the accumulation of amyloid-β in the brain are still not fully understood [2,3,4]. Looking for the proposed mechanisms involved in AD (Figure 2) several ones could be defined as potential targets for preventive/treatments strategies.
Major candidates’ therapeutic targets to lower amyloid-β in a preventive mode are secretases. Recent lines of research in the search for AD treatments, include β- and γ-secretase inhibitors and enhancers of α-secretase expression. A study with a mice model of AD shows that α-secretase activity is elevated in the brain of animals treated with Cabernet Sauvignon compared to ethanol-treated control [6]. α-Secretase is also elevated in primary neurons obtained from those mice [5]. Similar results are found in both in vitro and in vivo studies with resveratrol [7,8], quercetin [9], myricetin [10] and hydroxycinnamate compounds [11]. Several in vitro studies show that wine polyphenols are able of block β-Secretase (BACE 1) activity to decrease Aβ accumulation. However, few studies were carried out with animals to confirm that wine polyphenols could inhibit BACE 1. Analysing those in vivo studies, we can conclude that more experiments are needed to clarify whether BACE 1 can be a molecular target for wine polyphenols (1). In last year’s researchers are searching for γ-secretase inhibitors since this is a promising strategy for disease modification. Regarding wine polyphenols only in vitro studies with resveratrol were carried out and again different results are reported. Two studies show that resveratrol decrease γ-secretase processing activity [12, 13] and one study shows that resveratrol does not inhibit Aβ production, partly because it has no effect on the Aβ-producing enzymes β- and γ-secretases [14].


Figure 2. Diagrammatic representation of pathogenic mechanisms involved in Alzheimer’s disease.
Aβ, amyloid beta; Aβo, amyloid beta oligomers; APP, amyloid precursor protein; IL-1β, interleukin 1
beta; IFN-γ, interferon gamma; LPR1, low-density lipoprotein receptor-related protein 1; ROS,
reactive oxygen species; TNF-α, tumor necrosis factor alpha.

Preventive and treatment options targeting amyloid aggregation and/or clearance are under study. Regarding wine polyphenols most of the studies used resveratrol that shows potential to both inhibition of Aβ oligomers aggregation and its clearance from the nervous system [1].
Tau protein is normally synthesized by neuronal cells to stabilize the microtubules for proper functioning of the neurons (Figure 2). So, targeting tau protein may prove to be a good therapeutic intervention. Neuroprotective effects of resveratrol also result from the inhibition of tau protein hyperphosphorylation, as it was observed cell nervous cell lines [15, 16]. Recently, some studies indicated the ability of quercetin [17], anthocyanins [18] and caffeic acid [19] to decrease tau protein hyperphosphorylation and thereby to attenuate the associated neuropathology.
Recent studies confirmed the influence of reactive oxygen species (ROS) on the development of AD. Targeting oxidative stress and increasing antioxidant defences of the brain would be an important strategy for maintaining survival of brain structure. Therefore, there has been an increase of interest in the therapeutic potential of polyphenols, especially resveratrol. As reviewed by me and David [1] It is known that resveratrol reduces ROS production in brain by:
-preventing nuclear factor-κB (NF-κB) activation;
-activating AMPK;
-reducing both lipid peroxidation levels and oxidative stress induced by Aβ senile plaques;
-downregulating inducible nitric oxide synthase (iNOS);
-inducing heme oxygenase 1 (HO-1);
-restoring intracellular antioxidant enzymes;
-reversing Aβ-induced malondialdehyde (MDA) overproduction derived from the lipid membrane oxidation.
Not only resveratrol but also the quercetin, (+)-catechin, epicatechin and myricetin are important in the prevention of neuronal damages by balancing oxidative and anti-oxidative status.
As suggested by epidemiological studies moderate consumption of wine, an element of the Mediterranean diet, is one of the main factors behind the neuroprotective effects observed in some populations [1]. Most of pre-clinical studies evaluated wine neuroprotection indirectly by analysing effects of the phenolic compounds of wine, mainly resveratrol. It is important to highlight that wine is a complex chemical mixture (Figure 1), therefore preventive/therapeutic efficacy of wine is due a combination of neuroprotective effects of wine phenolic compounds. In conclusion, wine could modulate multiple targets simultaneously involved in AD helping to prevent or slow age-related neurodegenerative diseases.
Those interested in a longer length report can download the working paper at:



Paula Silva
Assistant Professor in the Laboratory of Histology and Embryology, Department of Microscopy, in the Institute of Biomedical Sciences Abel Salazar (ICBAS) of University of Porto (UPorto). Teaching experience covers: Histology and Embryology (Human and Comparative), Animal Models of Human Disease, and Science Communication. Director of the continuing training course “Science communication - Life and health sciences” (6ECTS) and of the continuing training unit “Animal Models of Human Disease” (6ECTS). She obtained her PhD in Biomedical Sciences in UPorto. Paula Silva presents in her CV 18 original articles published in journals indexed in the Science Citation Index (SCI), 1 book chapter, participation in some I&DT projects, and numerous works in many national and international congress. At present, her main research topic is the influence of moderate consumption of wine on chronic diseases, particularly, neurodegenerative diseases. 


1.Silva, P.; Vauzour, D. Wine polyphenols and neurodegenerative diseases: an update on the molecular mechanisms underpinning their protective effects. Beverages 2018, 4(4), 96.
2.Selkoe, D.J.; Hardy, J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO molecular medicine 2016, 8, 595-608, doi:10.15252/emmm.201606210.
3.Li, Q.; Barres, B.A. Microglia and macrophages in brain homeostasis and disease. Nature reviews. Immunology 2018, 18, 225-242, doi:10.1038/nri.2017.125.
4.Congdon, E.E.; Sigurdsson, E.M. Tau-targeting therapies for Alzheimer disease. Nature reviews. Neurology 2018, 10.1038/s41582-018-0013-z, doi:10.1038/s41582-018-0013-z.
5.Wang, J.; Ho, L.; Zhao, Z.; Seror, I.; Humala, N.; Dickstein, D.L.; Thiyagarajan, M.; Percival, S.S.; Talcott, S.T.; Pasinetti, G.M. Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2006, 20, 2313-2320, doi:10.1096/fj.06-6281com.
6.Wang, J.; Ho, L.; Zhao, Z.; Seror, I.; Humala, N.; Dickstein, D.L.; Thiyagarajan, M.; Percival, S.S.; Talcott, S.T.; Pasinetti, G.M. Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2006, 20, 2313-2320, doi:10.1096/fj.06-6281com.
7.Porquet, D.; Casadesus, G.; Bayod, S.; Vicente, A.; Canudas, A.M.; Vilaplana, J.; Pelegri, C.; Sanfeliu, C.; Camins, A.; Pallas, M., et al. Dietary resveratrol prevents Alzheimer's markers and increases life span in SAMP8. Age (Dordrecht, Netherlands) 2013, 35, 1851-1865, doi:10.1007/s11357-012-9489-4.
8.Corpas, R.; Grinan-Ferre, C.; Rodriguez-Farre, E.; Pallas, M.; Sanfeliu, C. Resveratrol Induces Brain Resilience Against Alzheimer Neurodegeneration Through Proteostasis Enhancement. Molecular neurobiology 2018, 10.1007/s12035-018-1157-y, doi:10.1007/s12035-018-1157-y.
9.Martin-Aragon, S.; Jimenez-Aliaga, K.L.; Benedi, J.; Bermejo-Bescos, P. Neurohormetic responses of quercetin and rutin in a cell line over-expressing the amyloid precursor protein (APPswe cells). Phytomedicine : international journal of phytotherapy and phytopharmacology 2016, 23, 1285-1294, doi:10.1016/j.phymed.2016.07.007.
10.Shimmyo, Y.; Kihara, T.; Akaike, A.; Niidome, T.; Sugimoto, H. Multifunction of myricetin on A beta: neuroprotection via a conformational change of A beta and reduction of A beta via the interference of secretases. Journal of neuroscience research 2008, 86, 368-377, doi:10.1002/jnr.21476.
11.Huang, Y.; Jin, M.; Pi, R.; Zhang, J.; Chen, M.; Ouyang, Y.; Liu, A.; Chao, X.; Liu, P.; Liu, J., et al. Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells. Neuroscience letters 2013, 535, 146-151, doi:10.1016/j.neulet.2012.12.051.
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