Determination of ibuprofen enantiomers in breast milk using vortex-assisted matrix solid-phase dispersion and direct chiral liquid chromatography

A mixture of B-cyclodextrin (B-CD) and primary and secondary amine (PSA) sorbents was employed for the extraction and quantification of ibuprofen enantiomers from human breast milk, combining a vortex-assisted matrix solid-phase dispersion method (MSPD) and direct chiral liquid chromatography (CLC) with ultraviolet detection (UV). The MSPD sample preparation procedure was optimized focusing on both the type and amount of dispersion/sorption sorbents and the nature of the elution solvent, in order to obtain acceptable recoveries and avoiding enantiomer conversion. These MSPD parameters were optimized with the aid of an experimental design approach. Hence, a factorial design was used for identification of the main variables affecting the extraction process of ibuprofen enantiomers. Under optimum selected conditions, MSPD combined with direct CLC-UV was successfully applied for ibuprofen enantiomeric determination in breast milk at enantiomer levels between 0.15 and 6.0 µg∙g-1. The proposed analytical method also provided good repeatability, with relative standard deviations of 6.4 % and 8.3 % for the intra-day and inter-day precision, respectively

Screening the extraction process of phenolic compounds from pressed grape seed residue: Towards an integrated and sustainable management of viticultural waste

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

Novel Rivastigmine Derivatives as Promising Multi-Target Compounds for Potential Treatment of Alzheimer’s Disease

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.Depto. de Química AnalíticaFac. de Ciencias QuímicasTRUEPortuguese Fundação para a Ciência e Tecnologia (FCT)Ministerio de Ciencia e InnovaciónComunidad de Madrid and European funding from FSE and FEDER programsMinisterio de Ciencia, Innovación y UniversidadesErasmus+ programpu

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 lt 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.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020); C. L. Roriz PhD’s grant (SFRH/BD/117995/2016), L. Barros to FCT, P.I., through the institutional scientific employment program-contract for their contract and the individual scientific employment program-contract for S.A. Heleno’s contract. To Eramus + grant (P BRAGAC01) and the Complutense University of Madrid, Spain for the preodoctoral grant [CT17/17-CT18/17] of E. Gómez-Mejía. In addition, to the Complutense University of Madrid, Spain for the preodoctoral grant [CT17/17-CT18/17] of E. Gómez-Mejía. In addition, to the companies Ponto Agricola Lda. (Portugal) and Terras Gaudas (Spain) for providing the sample by-products. The authors are grateful to FEDER-Interreg España-Portugal programme for financial support through the project 0377_Iberphenol_6_E.info:eu-repo/semantics/publishedVersio

Página web del grupo bilingüe de la Facultad de Educación para la enseñanza de las ciencias: elaboración, explotación y juicio crítico de los estudiantes de cara a la internacionalización de la docencia

Elaboración de una página web con material didáctico de Ciencias para el grupo bilingüe de Educación, que además sirve para ofrecer información para estudiantes que pudieran estar interesados en formar parte del grupo, incluyendo estudiantes extranjeros

Neuroprotective mechanisms of multitarget 7-aminophenanthridin-6(5H)-one derivatives against metal-induced amyloid proteins generation and aggregation

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

Desarrollos metodológicos en cromatografía líquida capilar y quiral aplicación a la determinación de herbicidas fenoxiácido en muestras complejas

Los herbicidas fenoxiácido son compuestos orgánicos de gran interés analítico, puesto que además de utilizarse con gran profusión como pesticidas de uso agrícola para el control de las malas hierbas de hoja ancha en una amplia variedad de cultivos, resultan tóxicos, incluso a bajas concentraciones, para el hombre y los organismos vivos.Su separación y determinación se ha llevado a cabo mediante cromatografía líquida capilar con temperatura programada o gradiente de composición de fase móvil y detección ultravioleta, inyectando grandes volúmenes de muestra y utilizando técnicas de focalización en cabeza de columna para obtener elevada sensibilidad.Para su análisis multiresidual en mentha pipperita y zumo de manzana a niveles del máximo permitido por la legislación vigente, en suelos a bajos niveles de mg/kg y en orina humana a niveles que permiten establecer el grado de contaminación de trabajadores ocupacionalmente expuestos, se han desarrollado diferentes metodologías de tratamiento de muestra basadas en la lixiviación con ultrasonidos y en la utilización de adsorbentes de extracción en fase sólida.Puesto que la toxicidad y acción herbicida es función de la forma química en que se encuentran y en el caso de presentar quiralidad, de su forma enantiomerica, los métodos cromatográficos desarrollados han permitido la separación y determinación de herbicidas fenoxiácido en forma ácida y de ésteres, así como la resolución enantiomérica de sus mezclas racémicas.Los estudios desarrollados en esta tesis doctoral han permitido la puesta a punto de nuevas metodologías cromatográficas para resolver los problemas de su determinación multiresidual en muestras complejas y para evaluar su incidencia en el medioambiente y en la salud humana. Además han demostrado las considerables ventajas analíticas de la utilización de columnas de diámetro interno reducido en las técnicas de cromatografía de líquidos