Tetraselmis chuii Edible Microalga as a New Source of Neuroprotective Compounds Obtained Using Fast Biosolvent Extraction.

Tetraselmis chuii is an EFSA-approved novel food and dietary supplement with increasing use in nutraceutical production worldwide. This study investigated the neuroprotective potential of bioactive compounds extracted from T. chuii using green biobased solvents (ethyl acetate, AcOEt, and cyclopentyl methyl ether, CPME) under pressurized liquid extraction (PLE) conditions and supercritical fluid extraction (SFE). Response surface optimization was used to study the effect of temperature and solvent composition on the neuroprotective properties of the PLE extracts, including anticholinergic activity, reactive oxygen/nitrogen species (ROS/RNS) scavenging capacity, and anti-inflammatory activity. Optimized extraction conditions of 40 °C and 34.9% AcOEt in CPME resulted in extracts with high anticholinergic and ROS/RNS scavenging capacity, while operation at 180 °C and 54.1% AcOEt in CPME yielded extracts with potent anti-inflammatory properties using only 20 min. Chemical characterization revealed the presence of carotenoids (neoxanthin, violaxanthin, zeaxanthin, α- and ß-carotene) known for their anti-cholinesterase, antioxidant, and anti-inflammatory potential. The extracts also exhibited high levels of omega-3 polyunsaturated fatty acids (PUFAs) with a favorable ω-3/ω-6 ratio (>7), contributing to their neuroprotective and anti-inflammatory effects. Furthermore, the extracts were found to be safe to use, as cytotoxicity assays showed no observed toxicity in HK-2 and THP-1 cell lines at or below a concentration of 40 µg mL-1. These results highlight the neuroprotective potential of Tetraselmis chuii extracts, making them valuable in the field of nutraceutical production and emphasize the interest of studying new green solvents as alternatives to conventional toxic solvents.

In vivo neuroprotective capacity of a Dunaliella salina extract - comprehensive transcriptomics and metabolomics study.

In this study, an exhaustive chemical characterization of a Dunaliella salina (DS) microalga extract obtained using supercritical fluids has been performed, and its neuroprotective capacity has been evaluated in vivo using an Alzheimer's disease (AD) transgenic model of Caenorhabditis elegans (strain CL4176). More than 350 compounds were annotated in the studied DS extract, with triacylglycerols, free fatty acids (FAs), carotenoids, apocarotenoids and glycerol being the most abundant. DS extract significantly protects C. elegans in a dose-dependent manner against Aß-peptide paralysis toxicity, after 32 h, 53% of treated worms at 50 µg/mL were not paralyzed. This concentration was selected to further evaluate the transcriptomics and metabolomics changes after 26 h by using advanced analytical methodologies. The RNA-Seq data showed an alteration of 150 genes, mainly related to the stress and detoxification responses, and the retinol and lipid metabolism. The comprehensive metabolomics and lipidomics analyses allowed the identification of 793 intracellular metabolites, of which 69 were significantly altered compared to non-treated control animals. Among them, different unsaturated FAs, lysophosphatidylethanolamines, nucleosides, dipeptides and modified amino acids that have been previously reported as beneficial during AD progression, were assigned. These compounds could explain the neuroprotective capacity observed, thus, providing with new evidences of the protection mechanisms of this promising extract.

A Comprehensive Study on the Chemical Characterization and Neuroprotective Evaluation of Pracaxi Nuts Extracts Obtained by a Sustainable Approach.

The Amazonian Pentaclethra macroloba (Willd.) Kuntze nuts contain a lipidic fraction with health-promoting effects, but little is known about the bioactivity of other constituents. In this study, the lipidic fraction obtained using supercritical fluid extraction (SFE) with CO2 was chemically characterized by using lipidomics techniques. The SFE-CO2 residue, named as pracaxi cake, was re-extracted by pressurized liquid extraction following a biorefinery approach. Using a response surface methodology and based on the extraction yield and different in vitro assays, two optimum conditions were obtained: 80% and 12.5% of ethanol at 180 °C. Under these conditions, extraction yield and different in vitro measurements related to neuroprotection were assessed. Chemical characterization of these extracts suggested the presence of triterpenoid saponins and spermidine phenolamides, which were not previously reported in pracaxi nuts. These results suggest that pracaxi oil extraction by-products are a valuable source of bioactive compounds with neuroprotective potential.

Omics approaches to investigate the neuroprotective capacity of a Citrus sinensis (sweet orange) extract in a Caenorhabditis elegans Alzheimer's model.

Citrus sinensis by-products are a promising source of neuroprotective molecules. In this study, a pressurized liquid extract of Citrus by-products (PLE100) has been extensively characterized, and its neuroprotective capacity tested in the Caenorhabditis elegans strain CL4176, a validated in vivo model of Alzheimer's disease (AD). More than 450 compounds have been annotated in the extract, being triacylglycerols (TGs), stigmastanes, fatty acids (FAs) and carbohydrates the most abundant. The results demonstrate that worms PLE100-treated are significantly protected in a dose-dependent manner against the Aß-peptide paralysis toxicity. The RNA-Seq data showed an alteration of 294 genes mainly related to the stress response defense along with genes involved in the lipid transport and metabolism. Moreover, the comprehensive metabolomics study allowed the identification of 818 intracellular metabolites, of which 54 were significantly altered (mainly lipids). The integration of these and previous results provides with new evidences of the protection mechanisms of this promising extract.

Metabolomic Characterization of the Antiproliferative Activity of Bioactive Compounds from Fruit By-Products Against Colon Cancer Cells.

This methodological work demonstrates the potential of metabolomic approaches based on liquid chromatography coupled to high-resolution mass spectrometry (LC-ESI(+/-)-HRMS) to investigate the antiproliferative capacity of underexplored biomasses (e.g., Passiflora mollissima seeds and Physalys peruviana calyx), by evaluating the molecular changes induced at the metabolite expression levels on HT-29 human colon cancer cells. This protocol describes in detail the optimal conditions to obtain bioactive extracts by pressurized liquid extraction (PLE), the experimental procedure to grow and treat HT-29 human colon cancer cells and CCD-18Co normal human colon fibroblasts with the target extracts, the metabolites extraction from the cytosolic fraction, and subsequent metabolomic fingerprinting. After treatment for 48 and 72 h, the viability of HT-29 colon cancer cells is markedly affected, and metabolites can be extracted for investigation. Following the proposed metabolomic data analysis and interpretation workflow, altered cellular redox homeostasis, as well as inactivation or dysfunction on other metabolic pathways, constitutes valuable biological information to understand the mechanisms underlying the antiproliferative effect.

Synergic effect of natural deep eutectic solvent and high-intensity ultrasound on obtaining a ready-to-use genipin extract: Crosslinking and anti-neurodegenerative properties.

In this paper, genipin, an important natural crosslinker and anti-neurodegenerative compound, was extracted from unripe Genipa americana L., combining high-intensity ultrasound (HIUS) and natural deep eutectic solvents (NADESs). The extraction process conditions were evaluated step-by-step to reach the best genipin recovery. The obtained ready-to-use genipin-NADES extract was examined regarding its crosslinking properties and anti-neurodegenerative capacity. For the condictions tested, the highest genipin recovery was obtained using 40 % water and 60 % betaine:lactic acid NADES in molar ratio 1:3 (n/n) as the solvent, a solvent:feed ratio of 19 (w/w), and HIUS acoustic power of 14 ± 1 W. The HIUS-assisted extraction using NADES as solvent showed to be a promising and efficient green extraction technique to obtain genipin. The ready-to-use genipin-NADES extract presented crosslinking capacity and anticholinergic activity. These results indicate that genipin-NADES extract can be directly applied in hydrogels for drug delivery, films, tissue engineering, and others. Moreover, it can be used in food, supplements, and medicine to enhance their neuroprotective effect.

Neuroprotective Potential of Thinned Peaches Extracts Obtained by Pressurized Liquid Extraction after Different Drying Processes.

Genetic, environmental and nutritional factors are suggested as primary factors of Alzheimer's disease (AD), and secondary metabolites such as polyphenols present in thinned peaches are considered as good candidates for AD prevention. Thinned peaches are usually dried to avoid putrefaction, but the effects of the drying method and the extraction process on the polyphenol composition and the neuroprotective potential have never been addressed. In this work, a pressurized liquid extraction (PLE) method was optimized and applied to thinned peaches dried under different conditions, and their neuroprotective potential was evaluated in vitro. In addition, the PLE extracts were characterized via HPLC-Q-TOF-MS/MS, and a permeability assay was performed to evaluate the ability of the identified metabolites to cross the blood-brain barrier (BBB). The PLE extracts obtained from freeze-dried (FD) samples with 50% ethanol in water at 180 °C showed the best neuroprotective potential. Finally, among the 81 metabolites identified, isoferulic acid, 4-methyldaphnetin, coniferyl aldehyde and 3,4-dihydroxyacetophenone were found at higher concentrations in FD extracts. These metabolites are able to cross the BBB and are positively correlated with the neuroprotective potential, suggesting FD together with PLE extraction as the best combination to exploit the neuroprotective capacity of thinned peaches.

Impact Factor JUMPS After the 2020 COVID-19 Pandemic: A Retrospective Study in Radiology, Nuclear Medicine & Medical Imaging Journals.

ABSTRACT: One of the most widely applied methods for evaluating a research paper's quality is the impact factor (IF). The term JUMPS was applied to the IF in an article published in PubMed in 2021, describing an increase of more than 40% of IF. In this study, we aimed to compare the growth rate of IF JUMPS in Radiology, Nuclear Medicine & Medical Imaging in the last 6 years. This retrospective study calculated the growth rate (JUMP) in IF from 2015 to 2020. We used the Friedman and Wilcoxon signed ranks tests to calculate the statistically significant difference in IF from 2015 to 2020 and the 2019 to 2020 difference. We classified JUMPS in negative growth rate, quartiles, and journals with >100%. Three journals had more than 100% IF growth rate during 2020 ( Zeitschrift fur Medizinische Physik , Journal of the Belgian Society of Radiology , and Ultrasound Quarterly ). A 76% to 100% growth rate was observed in another 4 journals (3.2%), and 8 journals (6.3%) depicted a 51% to 75% percentage of change. Repeated measures analyses showed a significant difference ( P < 0.001). During the COVID-19 pandemic, several journals in the Radiology, Nuclear Medicine & Medical Imaging category increased their IF by 50%. Knowing the growing trends in this category might supplement the assessment of target journals for authors looking to submit their works.

Blood-Brain Barrier Permeability Study of Potential Neuroprotective Compounds Recovered From Plants and Agri-Food by-Products.

Plants and agri-food by-products represent a wide and renewable source of bioactive compounds with neuroprotective properties. In this research, various green extraction techniques were employed to recover bioactive molecules from Kalanchoe daigremontiana (kalanchoe), epicarp of Cyphomandra betacea (tamarillo), and cooperage woods from Robinia pseudoacacia (acacia) and Nothofagus pumilio (lenga), as well as a reference extract (positive control) from Rosmarinus officinalis L. (rosemary). The neuroprotective capacity of these plant extracts was evaluated in a set of in vitro assays, including enzymatic [acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and lipoxygenase (LOX)] and antioxidant [ABTS, and reactive oxygen and nitrogen species (ROS and RNS)] bioactivity tests. Extracts were also submitted to a parallel artificial membrane permeability assay mimicking the blood-brain barrier (PAMPA-BBB) and to two cell viability assays in HK-2 and SH-SY5Y cell lines. Comprehensive phytochemical profiling based on liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) analysis showed enriched content of phenolic and terpenoid compounds in the target extracts. Moreover, in vitro bioactivity tests showed promising neuroprotective capacity, particularly for supercritical-fluid extraction (SFE) extract from acacia (ABTS IC50 = 0.11 µg ml-1; ROS IC50 = 1.56 µg ml-1; AChE IC50 = 4.23 µg ml-1; BChE IC50 = 1.20 µg ml-1; and LOX IC50 = 4.37 µg ml-1), whereas PAMPA-BBB assays revealed high perfusion capacity of some representative compounds, such as phenolic acids or flavonoids. Regarding cytotoxic assays, tamarillo and rosemary SFE extracts can be considered as non-toxic, acacia SFE extract and lenga pressurized liquid extraction (PLE) extract as mild-cytotoxic, and kalanchoe as highly toxic extracts. The obtained results demonstrate the great potential of the studied biomass extracts to be transformed into valuable food additives, food supplements, or nutraceuticals with promising neuroprotective properties.

Study of the reaction between genipin and amino acids, dairy proteins, and milk to form a blue colorant ingredient.

Currently, one of the biggest challenges of the colorant industry is to obtain natural blue colorants. Among the different options, a blue pigment can be formed by a crosslinking reaction between genipin and primary amine groups. However, at the industrial level, obtaining an ingredient from pure compounds, such as amino acids, is economically unfeasible. The present work aimed to study the reaction and kinetics of the blue color formation, starting the study with pure compounds (genipin and amino acids) to more complex and cheaper natural sources, such as Genipa americana L. fruits and milk. The reaction kinetics of the monomers/dimers for different amino acids reacting with genipin was evaluated, as well as the preferential amino acid, genipin:amino acid ratio and pH, to obtain the most rapid and intense blue color. Finally, the blue pigment formed using milk and its proteins was characterized by SDS-PAGE. The results suggest that the reaction kinetic is influenced by the type and concentration of the amino acid used and the pH of the medium, which could facilitate the further standardization of the industrial process. We also suggested milk as an excellent reaction medium to obtain the colorant from genipin as it presents an ideal pH and favorable amino acid composition to facilitate the reaction.

Neuroprotective potential of terpenoid-rich extracts from orange juice by-products obtained by pressurized liquid extraction.

Pressurized liquid extraction (PLE) conditions were optimized to improve the recovery of orange (Citrus sinensis) by-products terpenoids. The neuroprotective potential of the PLE extracts were tested against a set of in-vitro assay (antioxidant (ABTS), reactive oxygen/nitrogen species (ROS/RNS)) as well as enzymatic tests (acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX)). Gas chromatography coupled to high-resolution mass spectrometry (GC-q-TOF-MS) analysis revealed a higher enrichment in mono- and sesquiterpenoids of the PLE extracts with the highest neuroprotection capacity. In-silico molecular docking analysis showed the specific interaction of representative terpenoids with enzymes active sites. The results demonstrate that the selected extract at 100 °C and 30 minutes possesses high antioxidant (ABTSIC50 = 13.5 µg mL-1; ROSIC50 = 4.4 µg mL-1), anti-cholinesterase (AChEIC50 = 137.1 vg  L-1; BChEIC50 = 147.0 µg mL-1) and anti-inflammatory properties (against IL-6 and LOXIC50 = 76.1 µg mL-1), with low cytotoxicity and protection against L-glutamic acid in cell models.

Metabolomics study of COVID-19 patients in four different clinical stages.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the coronavirus strain causing the respiratory pandemic COVID-19 (coronavirus disease 2019). To understand the pathobiology of SARS-CoV-2 in humans it is necessary to unravel the metabolic changes that are produced in the individuals once the infection has taken place. The goal of this work is to provide new information about the altered biomolecule profile and with that the altered biological pathways of patients in different clinical situations due to SARS-CoV-2 infection. This is done via metabolomics using HPLC-QTOF-MS analysis of plasma samples at COVID-diagnose from a total of 145 adult patients, divided into different clinical stages based on their subsequent clinical outcome (25 negative controls (non-COVID); 28 positive patients with asymptomatic disease not requiring hospitalization; 27 positive patients with mild disease defined by a total time in hospital lower than 10 days; 36 positive patients with severe disease defined by a total time in hospital over 20 days and/or admission at the ICU; and 29 positive patients with fatal outcome or deceased). Moreover, follow up samples between 2 and 3 months after hospital discharge were also obtained from the hospitalized patients with mild prognosis. The final goal of this work is to provide biomarkers that can help to better understand how the COVID-19 illness evolves and to predict how a patient could progress based on the metabolites profile of plasma obtained at an early stage of the infection. In the present work, several metabolites were found as potential biomarkers to distinguish between the end-stage and the early-stage (or non-COVID) disease groups. These metabolites are mainly involved in the metabolism of carnitines, ketone bodies, fatty acids, lysophosphatidylcholines/phosphatidylcholines, tryptophan, bile acids and purines, but also omeprazole. In addition, the levels of several of these metabolites decreased to "normal" values at hospital discharge, suggesting some of them as early prognosis biomarkers in COVID-19 at diagnose.

Metataxonomic and metabolomic evidence of biofilm homeostasis disruption related to caries: An in vitro study.

The ecological dysbiosis of a biofilm includes not only bacterial changes but also changes in their metabolism. Related to oral biofilms, changes in metabolic activity are crucial endpoint, linked directly to the pathogenicity of oral diseases. Despite the advances in caries research, detailed microbial and metabolomic etiology is yet to be fully clarified. To advance this knowledge, a meta-taxonomic approach based on 16S rRNA gene sequencing and an untargeted metabolomic approach based on an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis (UHPLC/Q-TOF-MS) were conducted. To this end, an in vitro biofilm model derived from the saliva of healthy participants were developed, under commensal and cariogenic conditions by adding sucrose as the disease trigger. The cariogenic biofilms showed a significant increase of Firmicutes phyla (p = 0.019), due to the significant increase in the genus Streptococcus (p = 0.010), and Fusobacter (p < 0.001), by increase Fusobacterium (p < 0.001) and Sphingomonas (p = 0.024), while suffered a decrease in Actinobacteria (p < 0.001). As a consequence of the shift in microbiota composition, significant extracellular metabolomics changes were detected, showed 59 metabolites of the 120 identified significantly different in terms of relative abundance between the cariogenic/commensal biofilms (Rate of change > 2 and FDR < 0.05). Forty-two metabolites were significantly higher in abundance in the cariogenic biofilms, whereas 17 metabolites were associated significantly with the commensal biofilms, principally related protein metabolism, with peptides and amino acids as protagonists, latter represented by histidine, arginine, l-methionine, glutamic acid, and phenylalanine derivatives.

In Vitro Study of the Blood-Brain Barrier Transport of Natural Compounds Recovered from Agrifood By-Products and Microalgae.

Agrifood by-products and microalgae represent a low-cost and valuable source of bioactive compounds with neuroprotective properties. However, the neuroprotective effectiveness of therapeutic molecules can be limited by their capacity to cross the blood-brain barrier (BBB) and reach the brain. In this research, various green extracts from Robinia pseudoacacia (ASFE), Cyphomandra betacea (T33), Coffea arabica (PPC1), Olea europaea L., (OL-SS), Citrus sinensis (PLE100) by-products and from the microalgae Dunaliella salina (DS) that have demonstrated in vitro neuroprotective potential were submitted to an in vitro BBB permeability and transport assay based on an immortalized human brain microvascular endothelial cells (HBMEC) model. Toxicity and BBB integrity tests were performed, and the transport of target bioactive molecules across the BBB were evaluated after 2 and 4 h of incubation using gas and liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (GC/LC-Q-TOF-MS). The HBMEC-BBB transport assay revealed a high permeability of representative neuroprotective compounds, such as mono- and sesquiterpenoids, phytosterols and some phenolic compounds. The obtained results from the proposed in vitro BBB cellular model provide further evidence of the neuroprotective potential of the target natural extracts, which represent a promising source of functional ingredients to be transferred into food supplements, food additives, or nutraceuticals with scientifically supported neuroprotective claims.

Capillary electromigration methods for food analysis and Foodomics: Advances and applications in the period February 2019-February 2021.

This work presents a revision of the main applications of capillary electromigration methods in food analysis and Foodomics. Articles that were published during the period February 2019-February 2021 are included. The work shows the multiple CE methods that have been developed and applied to analyze different types of molecules in foods. Namely, CE methods have been applied to analyze amino acids, biogenic amines, carbohydrates, chiral compounds, contaminants, DNAs, food additives, heterocyclic amines, lipids, secondary metabolites, peptides, pesticides, phenols, pigments, polyphenols, proteins, residues, toxins, vitamins, small organic and inorganic compounds, as well as other minor compounds. The last results on the use of CE for monitoring food interactions and food processing, including recent microchips developments and new applications of CE in Foodomics, are discussed too. The new procedures of CE to investigate food quality and safety, nutritional value, storage and bioactivity are also included in the present review work.

Study of the potential neuroprotective effect of Dunaliella salina extract in SH-SY5Y cell model.

Alzheimer's disease (AD) is the most common form of dementia caused by a progressive loss of neurons from different regions of the brain. This multifactorial pathophysiology has been widely characterized by neuroinflammation, extensive oxidative damage, synaptic loss, and neuronal cell death. In this sense, the design of multi-target strategies to prevent or delay its progression is a challenging goal. In the present work, different in vitro assays including antioxidant, anti-inflammatory, and anti-cholinergic activities of a carotenoid-enriched extract from Dunaliella salina microalgae obtained by supercritical fluid extraction are studied. Moreover, its potential neuroprotective effect in the human neuron-like SH-SY5Y cell model against remarkable hallmarks of AD was also evaluated. In parallel, a comprehensive metabolomics study based on the use of charged-surface hybrid chromatography (CSH) and hydrophilic interaction liquid chromatography (HILIC) coupled to high-resolution tandem mass spectrometry (Q-TOF MS/MS) was applied to evaluate the effects of the extract on the metabolism of the treated cells. The use of advanced bioinformatics and statistical tools allowed the identification of more than 314 metabolites in SH-SY5Y cells, of which a great number of phosphatidylcholines, triacylglycerols, and fatty acids were significantly increased, while several phosphatidylglycerols were decreased, compared to controls. These lipidomic changes in cells along with the possible role exerted by carotenoids and other minor compounds on the cell membrane might explain the observed neuroprotective effect of the D. salina extract. However, future experiments using in vivo models to corroborate this hypothesis must be carried out.

Neuroprotective Potential of Tamarillo (Cyphomandra betacea) Epicarp Extracts Obtained by Sustainable Extraction Process.

Tamarillo (Cyphomandra betacea (Cav.) Sendt.), or tree tomato, is a tropical fruit from the Andean region of South America; it is highly rich in vitamins, minerals, and polyphenolic compounds. In this study, extracts from tamarillo epicarp (TE) were obtained by pressurized liquid extraction (PLE), and their in-vitro neuroprotective potential was assessed. A central composite design with response surface methodology was performed to optimize PLE as a function of solvent composition and temperature. Selected response variables were extraction yield, total phenolic content (TPC), total flavonoid content (TFC), total carotenoid content (TCC), antioxidant (ABTS), and anti-inflammatory (LOX) activities, and anti-acetylcholinesterase (AChE) inhibitory capacity. According to the desirability function, the optimal conditions were 100% ethanol and 180°C with a 0.87 desirability value. Next, the anti-butyrylcholinesterase enzyme (BChE), reactive oxygen species (ROS), and reactive nitrogen species (RNS) inhibition as well as cytotoxicity in HK-2, THP-1 monocytes, and SH-5YSY neuroblastoma cell lines were studied for the TE extract obtained under optimized conditions. The optimum TE extract provided the following results: extraction yield (36.25%), TPC (92.09 mg GAE/g extract), TFC (4.4 mg QE/g extract), TCC (107.15 mg CE/g extract), antioxidant capacity (ABTS, IC50 = 6.33 mg/ml extract), LOX (IC50 = 48.3 mg/ml extract), and AChE (IC50 = 97.46 mg/ml extract), and showed no toxicity at concentration up to 120 µg/ml extract for all the tested cell lines. Finally, chemical characterization by liquid chromatography-tandem mass spectrometry (UHPLC-q-TOF-MS/MS) of the optimum TE extract exhibited an important presence of hydroxycinnamic acid derivatives and other phenolic acids as well as quercetin hexoside and rutin, as main metabolites responsible for the observed biological properties. All these results suggested that TE, which represents between 8 and 15% of the total fruit, could become a promising natural by-product with a potential "multitarget" activity against Alzheimer's disease.

In vitro Neuroprotective Potential and Lipidomics Study of Olive Leaves Extracts Enriched in Triterpenoids.

Alzheimer's Disease (AD) is the most common form of dementia that is associated with extracellular amyloid beta (Aß) plaque formation. Genetic, environmental, and nutrition factors have been suggested as contributors to oxidative stress and neuroinflammation events that are connected to AD etiology, and secondary metabolites, such as triterpenes, have shown promising results in AD prevention. In this work, the neuroprotective and anti-inflammatory potential of an olive leaves fraction enriched in triterpenoid compounds obtained using supercritical fluid extraction (SFE) and dynamic adsorption/desorption using sea sand as adsorbent has been performed. In addition, a comprehensive lipidomics study of the response of SH-SY5Y neuroblastoma cell line to this fraction was carried out using advanced analytical methodologies, namely, charged-surface hybrid chromatography-quadrupole-time of flight mass spectrometry (CSH-Q-TOF MS/MS). The use of freely available lipidomic annotation tools and databases, and stringent cut-off filters allowed the annotation of more than 250 intracellular lipids. Advanced bioinformatics and statistical tools showed a number of phosphatidylcholines and phosphatidylethanolamines significantly increased, which could explain the protection against the cell death caused by Aß1-42. Moreover, several triacylglycerols were found decreased. These results suggest triterpenoids from olive leaves as good neuroprotective candidates, and open a new gate for future experiments using in vivo models to corroborate this hypothesis.

Neuroprotective Effect of Terpenoids Recovered from Olive Oil By-Products.

The neuroprotective potential of 32 natural extracts obtained from olive oil by-products was investigated. The online coupling of supercritical fluid extraction (SFE) and dynamic adsorption/desorption allowed the selective enrichment of olive leaves extracts in different terpenoids' families. Seven commercial adsorbents based on silica gel, zeolite, aluminum oxide, and sea sand were used with SFE at three different extraction times to evaluate their selectivity towards different terpene families. Collected fractions were analyzed by gas chromatography coupled to quadrupole-time-of-flight mass spectrometry (GC-QTOF-MS) to quantify the recoveries of monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and triterpenes (C30). A systematic analysis of the neuroprotective activity of the natural extracts was then carried out. Thus, a set of in vitro bioactivity assays including enzymatic (acetylcholinesterase (AChE), butyrylcholinesterase (BChE)), and anti-inflammatory (lipoxidase (LOX)), as well as antioxidant (ABTS), and reactive oxygen and nitrogen species (ROS and RNS, respectively) activity tests were applied to screen for the neuroprotective potential of these extracts. Statistical analysis showed that olive leaves adsorbates from SS exhibited the highest biological activity potential in terms of neuroprotective effect. Blood-brain barrier permeation and cytotoxicity in HK-2 cells and human THP-1 monocytes were studied for the selected olive leaves fraction corroborating its potential.