Examinando por Autor "Rosales-Conrado, Noelia"

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A Comprehensive Analytical Review of Polyphenols: Evaluating Neuroprotection in Alzheimer’s Disease
(MDPI, 2024-05-28) Vicente-Zurdo, David; Gómez-Mejía, Esther; Rosales-Conrado, Noelia; León-González, María Eugenia
Alzheimer’s Disease (AD), a prevalent neurodegenerative disorder, is the primary cause of dementia. Despite significant advancements in neuroscience, a definitive cure or treatment for this debilitating disease remains elusive. A notable characteristic of AD is oxidative stress, which has been identified as a potential therapeutic target. Polyphenols, secondary metabolites of plant origin, have attracted attention due to their potent antioxidant properties. Epidemiological studies suggest a correlation between the consumption of polyphenol-rich foods and the prevention of chronic diseases, including neurodegenerative disorders, which underscores the potential of polyphenols as a therapeutic strategy in AD management. Hence, this comprehensive review focuses on the diverse roles of polyphenols in AD, with a particular emphasis on neuroprotective potential. Scopus, ScienceDirect, and Google Scholar were used as leading databases for study selection, from 2018 to late March 2024. Analytical chemistry serves as a crucial tool for characterizing polyphenols, with a nuanced exploration of their extraction methods from various sources, often employing chemometric techniques for a holistic interpretation of the advances in this field. Moreover, this review examines current in vitro and in vivo research, aiming to enhance the understanding of polyphenols’ role in AD, and providing valuable insights for forthcoming approaches in this context.
Ability of selenium species to inhibit metal-induced Aβ aggregation involved in the development of Alzheimer’s disease
(Springer, 2020-04-22) Vicente-Zurdo, David; Romero-Sánchez, Iván; Rosales-Conrado, Noelia; León-González, María Eugenia; Madrid, Yolanda
Extracellular accumulation of amyloid beta peptide (Aβ) is believed to be one of the main factors responsible for neurodegeneration in Alzheimer’s disease (AD). Metals could induce Aβ aggregation, by their redox activity or binding properties to amyloid β fibrils, leading to their accumulation and deposition outside neurons. For this reason, metal chelation may have an acknowledged part to play in AD prevention and treatment. In the current work, the role of different selenium species, including selenium nanoparticles, in Aβ aggregation, was studied by evaluating their metal-chelating properties and their ability both to inhibit metal-induced Aβ1–42 aggregation fibrils and to disaggregate them once formed. Transition biometals such as Fe(II), Cu(II), and Zn(II) at 50 μM were selected to establish the in vitro models. The DPPH assay was used to determine the antioxidant capacity of the evaluated selenium species. Selenium nanoparticles stabilized with chitosan (Ch-SeNPs) and with both chitosan and chlorogenic acid polyphenol (CGA@ChSeNPs) showed the highest antioxidant properties with EC50 of 0.9 and 0.07 mM, respectively. UV–Vis and d1(UV–Vis) spectra also revealed that selenium species, in particular selenomethionine (SeMet), were able to interact with metals. Regarding Aβ1–42 incubation experiments, Fe(II), Cu(II), and Zn(II) induced Aβ aggregation, in a similar way to most of the evaluated selenium species. However, Ch-SeNPs produced a high inhibition of metal-induced Aβ aggregation, as well as a high disaggregation capacity of Aβ fibrils in both the presence and absence of biometals, in addition to reducing the length and width (20% of reduction in the presence of Zn(II)) of the generated Aβ fibrils
Cytotoxicity, uptake and accumulation of selenium nanoparticles and other selenium species in neuroblastoma cell lines related to Alzheimer's disease by using cytotoxicity assays, TEM and single cell-ICP-MS
(Elsevier, 2023-04-08) Vicente-Zurdo, David; Gómez-Gómez, Beatriz; Romero-Sánchez, Iván; Rosales-Conrado, Noelia; León-González, María Eugenia; Madrid, Yolanda
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, representing 80% of the total dementia cases. The “amyloid cascade hypothesis” stablishes that the aggregation of the beta-amyloid protein (Aβ42) is the first event that subsequently triggers AD development. Selenium nanoparticles stabilized with chitosan (Ch-SeNPs) have demonstrated excellent anti-amyloidogenic properties in previous works, leading to an improvement of AD aetiology. Here, the in vitro effect of selenium species in AD model cell line has been study to obtain a better assessment of their effects in AD treatment. For this purpose, mouse neuroblastoma (Neuro-2a) and human neuroblastoma (SH-SY5Y) cell lines were used. Cytotoxicity of selenium species, such as selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys) and Ch-SeNPs, has been determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry methods. Intracellular localisation of Ch-SeNPs, and their pathway through SH-SY5Y cell line, have been evaluated by transmission electron microscopy (TEM). The uptake and accumulation of selenium species by both neuroblastoma cell lines have been quantified at single cell level by single cell- Inductively Coupled Plasma with Mass Spectrometry detection (SC-ICP-MS), with a previous optimisation of transport efficiency using gold nanoparticles (AuNPs) ((69 ± 3) %) and 2.5 mm calibration beads ((92 ± 8) %). Results showed that Ch-SeNPs would be more readily accumulated by both cell lines than organic species being accumulation ranges between 1.2 and 89.5 fg Se cell−1 for Neuro-2a and 3.1–129.8 fg Se cell−1 for SH-SY5Y exposed to 250 μM Ch-SeNPs. Data obtained were statistically treated using chemometric tools. These results provide an important insight into the interaction of Ch-SeNPs with neuronal cells, which could support their potential use in AD treatment
Discovery of 7-aminophenanthridin-6-one as a new scaffold for matrix metalloproteinase inhibitors with multitarget neuroprotective activity
(Elsevier, 2021-01-15) Rocchi, Damiano; Blázquez-Barbadillo, Cristina; Agamennone, Mariangela; Laghezza, Antonio; Tortorella, Paolo; Vicente-Zurdo, David; Rosales-Conrado, Noelia; Moyano, Paula; del Pino, Javier; González, Juan F; Menéndez, J. Carlos
Matrix metalloproteinases (MMPs) are zinc-dependent hydrolytic enzymes of great biological relevance, and some of them are key to the neuroinflammatory events and the brain damage associated to stroke. Non-zinc binding ligands are an emerging trend in drug discovery programs in this area due to their lower tendency to show off-target effects. 7-Amino-phenanthridin-6-one is disclosed as a new framework able to inhibit matrix metalloproteinases by binding to the distal part of the enzyme S1’ site, as shown by computational studies. A kinetic study revealed inhibition to be noncompetitive. Some of the compounds showed some degree of selectivity for the MMP-2 and MMP-9 enzymes, which are crucial for brain damage associated to ischemic stroke. Furthermore, some compounds also had a high neuroprotective activity against oxidative stress, which is also very relevant aspect of ischaemic stroke pathogenesis, both decreasing lipid peroxidation and protecting against the oxidative stress-induced reduction in cell viability. One of the compounds, bearing a 2-thienyl substituent at C-9 and a 4-methoxyphenylamino at C-7, had the best-balanced multitarget profile and was selected as a lead on which to base future structural manipulation
Neuroprotective Action of Multitarget 7-Aminophenanthridin-6(5H)-one Derivatives against Metal-Induced Cell Death and Oxidative Stress in SN56 Cells
(American Chemical Society, 2021-08-30) Moyano, Paula; Vicente-Zurdo, David; Blázquez-Barbadillo, Cristina; Menéndez, J. Carlos; González, Juan F; Rosales-Conrado, Noelia; del Pino, Javier
Neurodegenerative diseases have been associated with brain metal accumulation, which produces oxidative stress (OS), matrix metalloproteinases (MMPs) induction, and neuronal cell death. Several metals have been reported to downregulate both the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the antioxidant enzymes regulated by it, mediating OS induction and neurodegeneration. Among a recently discovered family of multitarget 7-amino-phenanthridin-6-one derivatives (APH) the most promising compounds were tested against metal-induced cell death and OS in SN56 cells. These compounds, designed to have chelating activity, are known to inhibit some MMPs and to present antioxidant and neuroprotective effects against hydrogen peroxide treatment to SN56 neuronal cells. However, the mechanisms that mediate this protective effect are not fully understood. The obtained results show that compounds APH1, APH2, APH3, APH4, and APH5 were only able to chelate iron and copper ions among all metals studied and that APH3, APH4, and APH5 were also able to chelate mercury ion. However, none of them was able to chelate zinc, cadmium, and aluminum, thus exhibiting selective chelating activity that can be partly responsible for their neuroprotective action. Otherwise, our results indicate that their antioxidant effect is mediated through induction of the Nrf2 pathway that leads to overexpression of antioxidant enzymes. Finally, these compounds exhibited neuroprotective effects, reversing partially or completely the cytotoxic effects induced by the metals studied depending on the compound used. APH4 was the most effective and safe compound.
Neuroprotective activity of selenium nanoparticles against the effect of amino acid enantiomers in Alzheimer’s disease
(Springer, 2022-08-19) Vicente-Zurdo, David; Rodríguez-Blázquez, Sandra; Gómez-Mejía, Esther; Rosales-Conrado, Noelia; León-González, María Eugenia; Madrid, Yolanda
Alzheimer’s disease (AD), the most prevalent neurodegenerative disease, is characterized by extracellular accumulation of amyloid-beta protein (Aβ), which is believed to be the very starting event of AD neurodegeneration. In this work, D-Phe, D-Ala, and D-Glu amino acids, which are the non-occurring enantiomeric form in the human body, and also D-Asp and DL-SeMet, have proved to be amyloidogenic regarding Aβ42 aggregation in TEM studies. These amyloidogenic amino acid enantiomers also widened Aβ42 fibrils up to 437% regarding Aβ42 alone, suggesting that Aβ42 aggregation is enantiomerically dependent. To inhibit enantiomeric-induced amyloid aggregation, selenium nanoparticles stabilized with chitosan (Ch-SeNPs) were successfully synthesized and employed. Thus, Ch-SeNPs reduced and even completely inhibited Aβ42 aggregation produced in the presence of some amino acid enantiomers. In addition, through UV–Vis spectroscopy and fluorescence studies, it was deduced that Ch-SeNPs were able to interact differently with amino acids depending on their enantiomeric form. On the other hand, antioxidant properties of amino acid enantiomers were evaluated by DPPH and TBARS assays, with Tyr enantiomers being the only ones showing antioxidant effect. All spectroscopic data were statistically analysed through experimental design and response surface analysis, showing that the interaction between the Ch-SeNPs and the amino acids studied was enantioselective and allowing, in some cases, to establish the concentration ratios in which this interaction is maximum
Neuroprotective mechanisms of multitarget 7-aminophenanthridin-6(5H)-one derivatives against metal-induced amyloid proteins generation and aggregation
(Elsevier, 2022-09) Moyano, Paula; Vicente-Zurdo, David; Blázquez-Barbadillo, Cristina; Menéndez, J. Carlos; González, Juan F; Rosales-Conrado, Noelia; del Pino, Javier
Brain's metals accumulation is associated with toxic proteins, like amyloid-proteins (Aβ), formation, accumulation, and aggregation, leading to neurodegeneration. Metals downregulate the correct folding, disaggregation, or degradation mechanisms of toxic proteins, as heat shock proteins (HSPs) and proteasome. The 7-amino-phenanthridin-6(5H)-one derivatives (APH) showed neuroprotective effects against metal-induced cell death through their antioxidant effect, independently of their chelating activity. However, additional neuroprotective mechanisms seem to be involved. We tested the most promising APH compounds (APH1-5, 10–100 μM) chemical ability to prevent metal-induced Aβ proteins aggregation; the APH1-5 effect on HSP70 and proteasome 20S (P20S) expression, the metals effect on Aβ formation and the involvement of HSP70 and P20S in the process, and the APH1-5 neuroprotective effects against Aβ proteins (1 μM) and metals in SN56 cells. Our results show that APH1-5 compounds chemically avoid metal-induced Aβ proteins aggregation and induce HSP70 and P20S expression. Additionally, iron and cadmium induced Aβ proteins formation through downregulation of HSP70 and P20S. Finally, APH1-5 compounds protected against Aβ proteins-induced neuronal cell death, reversing partially or completely this effect. These data may help to provide a new therapeutic approach against the neurotoxic effect induced by metals and other environmental pollutants, especially when mediated by toxic proteins
Novel Rivastigmine Derivatives as Promising Multi‐Target Compounds for Potential Treatment of Alzheimer’s Disease
(MDPI, 2022-06-26) Vicente-Zurdo, David; Rosales-Conrado, Noelia; León-González, María Eugenia; Brunetti, Leonardo; Piemontese, Luca; Raquel Pereira-Santos, A; Cardoso, Sandra M; Madrid, Yolanda; Chaves, Sílvia; Santos, M. Amélia
Alzheimer’s disease (AD) is the most serious and prevalent neurodegenerative disorder still without cure. Since its aetiology is diverse, recent research on anti‐AD drugs has been focused on multi‐target compounds. In this work, seven novel hybrids (RIV–BIM) conjugating the active moiety of the drug rivastigmine (RIV) with 2 isomeric hydroxyphenylbenzimidazole (BIM) units were developed and studied. While RIV assures the inhibition of cholinesterases, BIM provides further appropriate properties, such as inhibition of amyloid β‐peptide (Aβ) aggregation, antioxidation and metal chelation. The evaluated biological properties of these hybrids included antioxidant activity; inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and Aβ42 aggregation; as well as promotion of cell viability and neuroprotection. All the compounds are better inhibitors of AChE than rivastigmine (IC50 = 32.1 μM), but compounds of series 5 are better inhibitors of BChE (IC50 = 0.9−1.7 μM) than those of series 4. Series 5 also showed good capacity to inhibit self‐ (42.1−58.7%) and Cu(II)‐induced (40.3−60.8%) Aβ aggregation and also to narrow (22.4−42.6%) amyloid fibrils, the relevant compounds being 5b and 5d. Some of these compounds can also prevent the toxicity induced in SH‐SY5Y cells by Aβ42 and oxidative stress. Therefore, RIV– BIM hybrids seem to be potential drug candidates for AD with multi‐target abilities.
Screening the extraction process of phenolic compounds from pressed grape seed residue: Towards an integrated and sustainable management of viticultural waste
(Elsevier, 2022-11-01) Gómez-Mejía, Esther; Vicente-Zurdo, David; Rosales-Conrado, Noelia; León-González, María Eugenia; Madrid, Yolanda
The integrated valorisation of waste from the food chain to obtain value-added compounds with biological functionality will facilitate the transition to the era of a sustainable bioeconomy. To this end, an efficient matrix solid-phase dispersion (MSPD) extraction method was developed and optimized, using experimental factorial design and response surface methodology, for polyphenols recovery from pressed grape seeds obtained after the extraction of essential oils by cold pressing. Gallic, dihydroxybenzoic, p-coumaric and trans-ferulic acid, naringin, resveratrol, quercetin and kaempferol were quantified at 2.1–295 μg g−1 by capillary liquid chromatography coupled to a diode array detector and a mass analyser (cLC-DAD-MS). Furthermore, total antioxidant activity, free radical scavenging and lipid peroxidation suppression, together with the inhibition of beta-amyloid (Αβ42) protein aggregation, considered one of the main pathological effects of Alzheimer's disease, were evaluated. Potent lipid peroxidation inhibition (IC50 0.238 ± 0.003 ng g−1) was observed, along with the reduction of Αβ42 fibril width (9.4–54.8%) and aggregation. The results presented proved that the MSPD extraction method could be considered as an efficient and sustainable methodology to produce phenolic-rich extracts that may serve as an alternative antioxidant and neuroprotective ingredient for the food or pharmaceutical formulations, leading to the cascade valorisation of winery by-products.
The Potential of Plum Seed Residue: Unraveling the Effect of Processing on Phytochemical Composition and Bioactive Properties
(MDPI, 2024-01-19) Rodríguez-Blázquez, Sandra; Pedrera-Cajas, Laura; Gómez-Mejía, Esther; Vicente-Zurdo, David; Rosales-Conrado, Noelia; León-González, María Eugenia; Rodríguez-Bencomo, Juan José; Miranda, Rubén
Bioactive compounds extracted from plum seeds were identified and quantified, aiming to establish how the brandy manufacturing process affects the properties and possible cascade valorization of seed residues. Extraction with n-hexane using Soxhlet has provided oils rich in unsaturated fatty acids (92.24–92.51%), mainly oleic acid (72–75.56%), which is characterized by its heart-healthy properties. The fat extracts also contain tocopherols with antioxidant and anti-inflammatory properties. All the ethanol–water extracts of the defatted seeds contain neochlorogenic acid (90–368 µg·g−1), chlorogenic acid (36.1–117 µg·g−1), and protocatechuate (31.8–100 µg·g−1) that have an impact on bioactive properties such as antimicrobial and antioxidant. Anti-amyloidogenic activity (25 mg·mL−1) was observed in the after both fermentation and distillation extract, which may be related to high levels of caffeic acid (64 ± 10 µg·g−1). The principal component analysis showed that all plum seed oils could have potential applications in the food industry as edible oils or in the cosmetic industry as an active ingredient in anti-aging and anti-stain cosmetics, among others. Furthermore, defatted seeds, after both fermentation and distillation, showed the greatest applicability in the food and nutraceutical industry as a food supplement or as an additive in the design of active packaging.
Unlocking the in vitro neuroprotection of sloe residues phenolic extracts by bioanalytical and chemometric strategies
(Elsevier, 2025-01-15) Gómez-Mejía, Esther; Vicente-Zurdo, David; Rosales-Conrado, Noelia; León-González, María Eugenia
Wild fruits, particularly the underutilized sloe (Prunus spinosa), are gaining interest as natural antioxidants, with residues from liqueur production being a source of bioactive compounds. This study proposes a sustainable approach for valorizing sloe residues, seeds and skins, by employing an innovative green extraction method. HPLC-ESI-QTOF and spectrophotometric techniques were used to explore the phenolic profile, highlighting the predominance of quercetin, 2,3-dihydroxybenzoic and ferulic acids (9.7–57 μg·g−1). In addition, the presence of Cu, Zn and Ca was confirmed by atomic absorption spectroscopy. Simultaneously, their neuroprotective potential against Alzheimer's disease (AD) was studied by exploring the inhibition of beta-amyloid aggregation and oxidative stress cytoprotection in SH-SY5Y cell line, standing out 1 μg·g−1 and 10 μg·g−1 extracts of sloe skin. Phenolic composition was correlated with bioactivities by means of multivariate analysis. These results contributed to highlight the potential of this bio-residue as a neuroprotective agent against AD in pharmaceutical and nutraceutical industries.
Unravelling the in vitro and in vivo potential of selenium nanoparticles in Alzheimer's disease: A bioanalytical review
(Elsevier, 2024-03-01) Vicente-Zurdo, David; Rosales-Conrado, Noelia; León-González, María Eugenia
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and the accumulation of beta-amyloid plaques and tau tangles in the brain. Current therapies have limited efficacy, prompting the search for novel treatments. Selenium nanoparticles (SeNPs) have emerged as promising candidates for AD therapy due to their unique physicochemical properties and potential therapeutic effects. This review provides an overview of SeNPs and their potential application in AD treatment, as well as the main bioanalytical techniques applied in this field. SeNPs possess antioxidant and anti-inflammatory properties, making them potential candidates to combat the oxidative stress and neuroinflammation associated with AD. Moreover, SeNPs have shown the ability to cross the blood-brain barrier (BBB), allowing them to target brain regions affected by AD pathology. Various methods for synthesizing SeNPs are explored, including chemical, physical and biological synthesis approaches. Based on the employment of algae, yeast, fungi, and plants, green methods offer a promising and biocompatible alternative for SeNPs production. In vitro studies have demonstrated the potential of SeNPs in reducing beta-amyloid aggregation and inhibiting tau hyperphosphorylation, providing evidence of their neuroprotective effects on neuronal cells. In vivo studies using transgenic mouse models and AD-induced symptoms have shown promising results, with SeNPs treatment leading to cognitive improvements and reduced amyloid plaque burden in the hippocampus. Looking ahead, future trends in SeNPs research involve developing innovative brain delivery strategies to enhance their therapeutic potential, exploring alternative animal models to complement traditional mouse studies, and investigating multi-targeted SeNPs formulations to address multiple aspects of AD pathology. Overall, SeNPs represent a promising avenue for AD treatment, and further research in this field may pave the way for effective and much-needed therapeutic interventions for individuals affected by this debilitating disease.