A Comprehensive Analytical Review of Polyphenols: Evaluating Neuroprotection in Alzheimer's Disease.

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.

Valorization of Defatted Cherry Seed Residues from Liquor Processing by Matrix Solid-Phase Dispersion Extraction: A Sustainable Strategy for Production of Phenolic-Rich Extracts with Antioxidant Potential.

The integrated valorization of food chain waste is one of the most promising alternatives in the transition to a sustainable bioeconomy. Thus, an efficient solid-phase matrix dispersion extraction method, using experimental factorial design and response surface methodology, has been developed and optimized for the recovery of polyphenols from defatted cherry seeds obtained after cherry liquor manufacture and subsequent fatty acid extraction, evaluating the effect of each processing step on the composition and phenolic content of sweet cherry residues. The phenolic extracts before fermentation showed the highest content of total polyphenols (TPC) and flavonoids (TFC) (3 ± 1 mg QE·g-1 and 1.37 ± 0.08 mg GAE·g-1, respectively), while the highest antioxidant capacity was obtained in the defatted seed extracts after both fermentation and distillation. In addition, high-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer (HPLC-ESI-QTOF-MS) was used to determine the phenolic profile. Dihydroxybenzoic acid, neochlorogenic acid, caffeic acid, and quercetin were the main phenolics found, showing differences in concentration between the stages of liquor production. The results underline the prospective of cherry by-products for obtaining phenol-rich bioactive extracts for possible use in different industrial sectors, offering a feasible solution for the cascade valorization of cherry agri-food waste.

Valorization of Citrus reticulata Blanco Peels to Produce Enriched Wheat Bread: Phenolic Bioaccessibility and Antioxidant Potential.

The fortification of foods with bioactive polyphenols aims to improve their functional properties and to provide health benefits. Yet, to exert their benefits, phenolic compounds must be released from the food matrix and absorbed by the small intestine after digestion, so assessing their bioaccessibility is crucial to determine their potential role. This work aims to incorporate Citrus reticulata Blanco peel extracts into wheat bread as a promising opportunity to increase their bioactive potential, along with supporting the sustainable management of citrus-industry waste. A control and a wheat bread enriched at 2% and 4% (w/v) with a phenolic extract from mandarin peels were prepared and analyzed for antioxidant activity and phenolic composition using LC-MS and UV-Vis spectrophotometry. In addition, in vitro digestion was performed, and the digested extracts were analyzed with HPLC-MS/MS. The results showed a significant increase in total flavonoid content (TFC, 2.2 ± 0.1 mg·g-1), antioxidant activity (IC50 = 37 ± 4 mg·g-1), and contents of quercetin, caffeic acid, and hesperidin in the 4% (w/v) enriched bread. Yet, most polyphenols were completely degraded after the in vitro digestion process, barring hesperidin (159 ± 36 µg·g-1), highlighting the contribution of citrus enrichment in the development of an enriched bread with antioxidant potential.

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.

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 (Aß42) 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.

Effect of Storage and Drying Treatments on Antioxidant Activity and Phenolic Composition of Lemon and Clementine Peel Extracts.

Obtaining polyphenols from horticultural waste is an emerging trend that enables the valorization of resources and the recovery of value-added compounds. However, a pivotal point in the exploitation of these natural extracts is the assessment of their chemical stability. Hence, this study evaluates the effect of temperature storage (20 and -20 °C) and drying methods on the phenolic composition and antioxidant activity of clementine and lemon peel extracts, applying HPLC-DAD-MS, spectrophotometric methods, and chemometric tools. Vacuum-drying treatment at 60 °C proved to be rather suitable for retaining the highest antioxidant activity and the hesperidin, ferulic, and coumaric contents in clementine peel extracts. Lemon extracts showed an increase in phenolic acids after oven-drying at 40 °C, while hesperidin and rutin were sustained better at 60 °C. Hydroethanolic extracts stored for 90 days preserved antioxidant activity and showed an increase in the total phenolic and flavonoid contents in lemon peels, unlike in clementine peels. Additionally, more than 50% of the initial concentration was maintained up to 51 days, highlighting a half-life time of 71 days for hesperidin in lemon peels. Temperature was not significant in the preservation of the polyphenols evaluated, except for in rutin and gallic acid, thus, the extracts could be kept at 20 °C.

A combined analytical-chemometric approach for the in vitro determination of polyphenol bioaccessibility by simulated gastrointestinal digestion.

In this study, an integrated characterisation through polyphenol and caffeine content and antioxidant activity was combined with chemometric analysis to assess the effects of simulated in vitro gastrointestinal digestion on the bioaccessibility of these bioactive compounds from nine different tea infusions. Tea infusions were characterised based on total flavonoids, total polyphenols and antioxidant activity, together with the determination of individual polyphenol content. Fourteen phenolic compounds, including phenolic acids, stilbenes and flavonoids, were selected based on their reported bioactivity and high accessibility, attributed to their low molecular weight. Both polyphenols and caffeine were initially monitored in raw tea infusions and through the different digestion stages (salivary, gastric and duodenal) by capillary high performance liquid chromatography coupled to diode array detection (cHPLC-DAD) and/or HPLC coupled to a triple quadrupole mass analyser (HPLC-MS/MS). Multivariate analysis of the studied bioactives, using principal component analysis and cluster analysis, revealed that the decaffeination process seems to increase the stability and concentration of the compounds evaluated during digestion. The greatest transformations occurred mainly in the gastric and duodenal stages, where low bioactivity indices (IVBA) were shown for resveratrol and caffeic acid (IVBA = 0%). In contrast, the polyphenols gallic acid, chlorogenic acid and quercetin gave rise to their availability in white, green and oolong infusion teas (IVBA > 90%). Furthermore, highly fermented black and pu-erh varieties could be designated as less bioaccessible environments in the duodenum with respect to the tested compounds.

A combined approach based on matrix solid-phase dispersion extraction assisted by titanium dioxide nanoparticles and liquid chromatography to determine polyphenols from grape residues.

A simple and efficient low-cost matrix solid phase dispersion (MSPD) extraction assisted by TiO2 nanoparticles and diatomaceous earth has been developed for the extraction of phenolic compounds from grape and grape pomace wastes. Experimental conditions for MSPD extraction were optimized by a factorial design and a surface response methodology. The simultaneous identification and quantification of eight main natural polyphenols (caffeic, p-coumaric, dihydroxybenzoic and gallic acid, rutin, resveratrol, quercetin and catechin) was possible by combining MSPD and capillary liquid chromatography coupled to a diode array detection and a mass simple quadrupole analyzer (cLC-DAD-MS). Good linearity and acceptable LOD (0.05-62 µg·g-1) and LOQ (0.2-207 µg·g-1) were obtained. The quantities of extracted polyphenols were within 2.4 and 333 µg·g-1, with catechin and rutin the most abundant compounds in grape pomace and grape wastes, respectively. Furthermore, considering the prospective uses of the winery bioresidues, the extracts have been characterised in terms of bioactive properties (several antioxidant activities and bacterial inhibition against Staphylococcus aureus, Escherichia coli and Pseudomona aeruginosa) and parameters such as total polyphenol and total flavonoid content. The high antioxidant activity (IC50 5.0 ± 0.4 µg ·g-1 against DPPH radical) and antibacterial activity (2.2 ± 0.3 mg·mL-1) suggests that the methodology developed is efficient, rapid and promising for the extraction of phenolic compounds with potential application as bioactive ingredients in food and cosmetic industries.

Anti-inflammatory activity of ethyl acetate and n-butanol extracts from Ranunculus macrophyllus Desf. and their phenolic profile.

ETHNOPHARMACOLOGICAL RELEVANCE: The members of the genus Ranunculus have counter-irritating properties and thus, they are traditionally used for treating anti-inflammatory disorders and other skin conditions. Ranunculus macrophyllus Desf. is a wild medicinal plant growing in Algeria and traditionally used to treat some cutaneous skin disorders. AIM: The aim of this study was to characterize the composition of the ethyl acetate and n-butanol extracts from Ranunculus macrophyllus Desf. as well as to elucidate and to compare their effect against acute skin inflammation. Moreover, both the antioxidant activity and the acute toxicity of the plant extracts were also studied. MATERIALS AND METHODS: Spectrophotometric and chromatographic methods were employed to identify and quantify phenolic compounds and triterpenoids from R. macrophyllus Desf. fractions. The antioxidant activity was estimated using the phosphomolebdenum, DPPH, reducing power and ß-carotene bleaching assays. The ethyl acetate and n-butanol extracts were screened for their anti-inflammatory activities using ex-vivo membrane stabilizing assays and in-vivo acute skin inflammation model. RESULTS: Ethyl acetate fraction showed the highest amounts of total phenolic compounds (413 ± 4 µg GAE/mg extract) and triterpenoids (70.4 ± 1.8 µg UAE/mg extract). Rutin, hesperidin, myricetin and kaempferol were the major compounds identified in the different fractions. Ethyl acetate fraction exhibited strong DPPH• radical scavenging ability (IC50 1.6 ± 0.2 µg/mL), high total antioxidant capacity (447 ± 7 µg AAE/mg extract) and reducing power (514 ± 8 µg AAE/mg extract). Ethyl acetate fraction inhibited (73.4 ± 0.3) % of linoleic acid peroxidation. Ethyl acetate and n-butanol fractions did not have any visible toxicity at 2000 mg/kg and presented excellent membrane stabilizing ability. The inhibition of xylene induced ear inflammation was (38 ± 4) % and (46 ± 1) % for RM-B and RM-EA, respectively. CONCLUSIONS: The high content of both phenolic compounds and triterpenoids combined with the remarkable anti-inflammatory effect and antioxidant activity of ethyl acetate and n-butanol extracts from R. macrophyllus Desf. support the wide spread use of this traditional plant on some skin disorders (inflammatory skin disorders).

Valorisation of black mulberry and grape seeds: Chemical characterization and bioactive potential.

Grape (Vitis vinifera L. var. Albariño) and mulberry (Morus nigra L.) seeds pomace were characterized in terms of tocopherols, organic acids, phenolic compounds and bioactive properties. Higher contents of tocopherols (28 ± 1 mg/100 g fw) were obtained in mulberry, whilst grape seeds were richer in organic acids (79 ± 4 mg/100 g fw). The phenolic analysis of hydroethanolic extracts characterised grape seeds by catechin oligomers (36.0 ± 0.3 mg/g) and mulberry seeds by ellagic acid derivatives (3.14 ± 0.02 mg/g). Both exhibited high antimicrobial activity against multiresistant Staphylococcus aureus MIC = 5 mg/mL) and no cytotoxicity against carcinogenic and non-tumour primary liver (PLP) cells. Mulberry seeds revealed the strongest inhibition (p < 0.05) against thiobarbituric reactive substances (IC50 = 23 ± 2 µg/mL) and oxidative haemolysis (IC50 at 60 min = 46.0 ± 0.8 µg/mL). Both seed by-products could be exploited for the developing of antioxidant-rich ingredients with health benefits for industrial application.

Ability of selenium species to inhibit metal-induced Aß aggregation involved in the development of Alzheimer's disease.

Extracellular accumulation of amyloid beta peptide (Aß) is believed to be one of the main factors responsible for neurodegeneration in Alzheimer's disease (AD). Metals could induce Aß aggregation, by their redox activity or binding properties to amyloid ß 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 Aß aggregation, was studied by evaluating their metal-chelating properties and their ability both to inhibit metal-induced Aß1-42 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 Aß1-42 incubation experiments, Fe(II), Cu(II), and Zn(II) induced Aß aggregation, in a similar way to most of the evaluated selenium species. However, Ch-SeNPs produced a high inhibition of metal-induced Aß aggregation, as well as a high disaggregation capacity of Aß 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 Aß fibrils. Graphical abstract.

Extraction of polyphenols and synthesis of new activated carbon from spent coffee grounds.

A valorization process of spent coffee grounds (SCG) was studied. Thus, a two-stage process, the first stage of polyphenols extraction and synthesis of a carbonaceous precursor and a subsequent stage of obtaining activated carbon (AC) by means of a carbonization process from the precursor of the previous stage, was performed. The extraction was carried out with a hydro-alcoholic solution in a pressure reactor, modifying time, temperature and different mixtures EtOH:H2O. To optimize the polyphenols extraction, a two-level factorial experimental design with three replicates at the central point was used. The best results were obtained by using a temperature of 80 °C during 30 min with a mixture of EtOH:H2O 50:50 (v/v). Caffeine and chlorogenic acid were the most abundant compounds in the analysed extracts, ranging from 0.09 to 4.8 mg∙g-1 and 0.06 to 9.7 mg∙g-1, respectively. Similarly, an experimental design was realized in order to analyze the influence of different variables in the AC obtained process (reaction time, temperature and KOH:precursor ratio). The best results were 1 h, 850 °C, and a mixture of 2.5:1. The obtained activated carbons exhibit a great specific surface (between 1600 m2∙g-1 and 2330 m2∙g-1) with a microporous surface. Finally, the adsorption capacity of the activated carbons was evaluated by methylene blue adsorption.

Extraction, identification and quantification of polyphenols from spent coffee grounds by chromatographic methods and chemometric analyses.

A solid-liquid extraction method using ethanol-water mixtures was combined with cLC-DAD, LC-MS/MS and chemometric analyses for establishing the optimum extraction conditions of valuable polyphenols from spent coffee grounds. Chlorogenic and p-coumaric acids were the most abundant polyphenols found, ranging from 0.02 to 4.8 mg g-1 and 0.173-0.50 mg g-1, respectively. In addition, total polyphenol content (9-29 mg GAE g-1 DW), total flavonoid content (11-27 mg QE g-1 DW), total antioxidant activity (0.3-7 mg GAE g-1 DW) and free radical scavenging ability (DPPH assay, 64-927 µg extract g-1 at EC50) of obtained extracts were determined. Response surface methodology allowed obtaining predictive models for the extraction of each individual polyphenol. On the other hand, multifactorial ANOVA was used to establish differences between coffee and spent coffee ground extracts. Principal component analysis was also employed to relate antioxidant activities, total polyphenol and total flavonoid contents with both the polyphenols extracted and the residue coffee type. The overall results suggested that spent coffee grounds could be reused as a promising, inexpensive and natural source of bioactive polyphenols with potential industrial applications, thus minimizing the waste disposal and environmental impact.

Citrus peels waste as a source of value-added compounds: Extraction and quantification of bioactive polyphenols.

A method combining solid-liquid extraction based on ethanolic aqueous solution, cLC-DAD and chemometrics, was performed to extract and quantify polyphenols from citrus peels. LC-MS/MS was also employed for chemical profiling. The effect of extraction variables on the recovery was examined by experimental factorial design. Data were evaluated using multifactorial-ANOVA, response surface analysis and Principal Component Analysis. trans-Ferulic and p-coumaric antioxidants were found in lower quantities (<1.4 mg·g-1) in all peel extracts. Narangin flavonoid was also identified in all samples, while rutin flavonol was determined in the concentration range of 3.3-4.7 mg·g-1. The most abundant polyphenol in the extracts obtained from all evaluated citrus samples was the flavanone hesperidin (280-673 mg·g-1). Furthermore, peel extracts were evaluated in terms of total polyphenol and flavonoid content, total antioxidant activity and DPPH free radical scavenging. The obtained results suggested that evaluated citrus peel by-products could be reused as a source of polyphenols and transformed into value-added products.

Determination of phenolic compounds in residual brewing yeast using matrix solid-phase dispersion extraction assisted by titanium dioxide nanoparticles.

A simple and efficient low-cost matrix solid-phase dispersion (MSPD) extraction based on TiO2 nanoparticles (NPs) and diatomaceous earth has been developed for the recovery of phenolic compounds from residual brewing yeast. Experimental conditions for MSPD extraction were optimized by an experimental design approach. A screening factorial design plus replicates at the center point, followed by surface response analysis were used. The simultaneous identification and quantification of eleven main natural polyphenols: caffeic, chlorogenic, p-coumaric, 3,4-dihydroxibenzoic, trans-ferulic and gallic acids, kaempferol, myricetin, naringin, quercetin and rutin, was possible by combining MSPD and capillary liquid chromatography couple to a diode array detection system (cLC-DAD) and liquid chromatography couple to a triple quadrupole analyzer (LC-MS/MS). Moreover, residual brewing yeast extracts were evaluated in terms of DPPH (1,1-diphenyl-2 picrylhydrazyl) free radical scavenging activity. Polyphenol-nanoparticle interaction was studied by UV-vis spectroscopy and electron transmission microscopy (TEM), pointing out a stable interplay that assists phenolic isolation. The extracted polyphenol quantities were within the 3.2-1,500 µg g-1 range, and the high antioxidant activity estimated suggested that developed MSPD is a successful, simple, efficient and rapid method for the extraction and recovery of bioactive phenolic compounds, which promotes the reuse and re-evaluation of brewing yeast agri-food by-products.

Simultaneous determination of the size and concentration of AgNPs in water samples by UV-vis spectrophotometry and chemometrics tools.

The combination of UV-vis spectrophotometry with a chemometric calibration tool based on partial least squares (PLS) has allowed us the development of a multivariate analytical method that simultaneously estimates the concentration and size of mixtures of silver nanoparticles (AgNPs) in environmental water samples. The method is based on changes in the surface plasmon resonance band (SPRB) of AgNPs when they form aggregated/assembled structures with L-cysteine (L-cys). Measurementts were performed by employed a fixed-time kinetics method that implies that the final spectra (response) are obtained by subtstracting the solutions spectra at fixed times. Optimization of experimental conditions affecting aggregation such as time, temperature, pH and concentration of aggregating substance was performed by experimental design and response surface methodologies (RSM). A multivariate calibration model using AgNPs of known diameter size ((20 ±â€¯3), (41 ±â€¯3), (59 ±â€¯5) and (79 ±â€¯7) nm) within a concentration range between 0.62 and 2.5 mg L-1 was constructed by using a mixture experimental design and PLS. The method was finally applied to estimate size and concentration of AgNPs in AgNPs-spiked river and tap water samples. Water samples were spiked with individual, binary and ternary mixtures of AgNPs of different sizes and by using two types of AgNPs: citrate-coated AgNPs (cit-AgNPs) and polyvinylpyrrolidone-coated AgNPs (PVP-AgNPs). A good correspondence was obtained between predicted values and the total amount of AgNPs added with recovery values ranged within 80-160% for the individual mixtures, 68-108% for the binary mixtures and 60-64% for the ternary mixtures of AgNPs. Finally, transmission electron microscopy (TEM) measurements were performed for those cases where discrepancies between the expected and the obtained values were observed. TEM micrographs evidenced the presence of agglomerates or aggregates of AgNPs in some of the mixtures or water tested.

Residual brewing yeast as a source of polyphenols: Extraction, identification and quantification by chromatographic and chemometric tools.

A method combining aqueous extraction, reversed-phase high-performance capillary liquid chromatography with photodiode array detection (cLC-DAD) and chemometric tools, was developed to determine phenolic compounds in residual brewing yeast. The effect of temperature, nature of extraction solvent and method for separation of extract solution were studied to optimize the extraction conditions on the basis of total phenolic content (TPC), total flavonoids content (TFC) and antioxidant capacity. Polyphenols were determined by cLC-DAD. Flavonols as rutin and kaempferol, flavonoids as naringin, phenolic acids as gallic acid and antioxidants as trans-ferulic and p-coumaric acids were found and quantified in the brewing residue. Data were subjected to evaluation using multifactor ANOVA and principal component analysis (PCA), both showing that lyophilization pretreatment affects the content of individual polyphenols and that residual brewing yeast contains higher polyphenol amounts than the liquid beer waste. The obtained results suggest that residual brewing yeast could be a source of polyphenols.