Farmacología

URI permanente para esta comunidadhttps://hdl.handle.net/11441/11024

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An Efficient and Practical Method for the Enantioselective Synthesis of Tertiary Trifluoromethyl Carbinols
(Wiley Online Library, 2018-03) Borrego Sánchez de la Cuesta, Lorenzo Gabriel; Recio Jiménez, Rocío; Alcarranza Saucedo, Manuel; Khiar, Noureddine; Fernández Fernández, Inmaculada; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía
An efficient sulfinamide/olefin based chiral ligand, MetSulfolefin, has been developed for the enantioselective rhodium-catalysed addition of aryl-boronic acids to trifluoromethyl ketones. This shelf-stable ligand is insensitive to air, oxygen and moisture, and it is obtained in only two high yielding steps from cheap commercially available (R)-tert-butanesulfinamide. The new ligand tolerates the use of hindered boronic acids and leads to the formation of a series of chiral trifluoromethyl-substituted tertiary carbinols in high yields and excellent enantioselectivities (up to >99% ee). (Figure presented.).
Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice
(Multidisciplinary Digital Publishing Institute (MDPI), 2023) Muñoz García, Rocío; Sánchez Hidalgo, Marina; Alcarranza Saucedo, Manuel; Vázquez Román, María Victoria; Álvarez de Sotomayor Paz, María; González Rodríguez, María Luisa; Andrés, María C.; Alarcón de la Lastra Romero, Catalina; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía; Instituto de Salud Carlos III
Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (w/w)) for 24 weeks. The presence of immune complexes was evaluated by immunohistochemistry and immunofluorescence. Endothelial dysfunction was studied in thoracic aortas. Signaling pathways and oxidative-inflammatory-related mediators were evaluated by Western blotting. Moreover, we studied epigenetic changes such as DNA methyltransferase (DNMT-1) and micro(mi)RNAs expression in renal tissue. Nutritional treatment with OLA reduced the deposition of immune complexes, ameliorating kidney damage. These protective effects could be related to the modulation of mitogen-activated protein kinases, the Janus kinase/signal transducer and transcription activator of transcription, nuclear factor kappa, nuclear-factor-erythroid-2-related factor 2, inflammasome signaling pathways, and the regulation of miRNAs (miRNA-126, miRNA-146a, miRNA-24-3p, and miRNA-123) and DNMT-1 expression. Moreover, the OLA-enriched diet normalized endothelial nitric oxide synthase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 overexpression. These preliminary results suggest that an OLA-supplemented diet could constitute a new alternative nutraceutical therapy in the management of SLE, supporting this compound as a novel epigenetic modulator of the immunoinflammatory response.
Effects of Oleacein, a New Epinutraceutical Bioproduct from Extra Virgin Olive Oil, in LPS-Activated Murine Immune Cells
(MDPI, 2022) Muñoz García, Rocío; Sánchez Hidalgo, Marina; Montoya García, Tatiana; Alcarranza Saucedo, Manuel; Ortega Vidal, Juan; Altarejos, Joaquin; Alarcón de la Lastra Romero, Catalina; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía
The present study was designed to evaluate the immunomodulatory effects of the secoiridoid from extra virgin olive oil, oleacein (OLA), deepening into the possible signaling pathways involved in LPS-activated murine peritoneal macrophages. Moreover, we have explored OLA-induced epigenetic changes in histone markers and related cytokine production in murine LPS-stimulated murine splenocytes. Murine cells were treated with OLA in the presence or absence of LPS (5 μg/mL) for 18 or 24 h. OLA modulated the oxidative stress and the inflammatory response produced by LPS stimulation in murine peritoneal macrophages, by the inhibition of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ, IL-17 and IL-18) and ROS production and the expression of pro-inflammatory enzymes such as iNOS, COX-2 and m-PGES1. These protective effects could be due to the activation of the Nrf-2/HO-1 axis and the inhibition of JAK/STAT, ERK and P38 MAPKs and inflammasome canonical and non-canonical signaling pathways. Moreover, OLA modulated epigenetic modifications throughout histone methylation deacetylation (H3K18ac) and (H3K9me3 and H3K27me) in LPS-activated spleen cells. In conclusion, our data present OLA as an interesting anti-inflammatory and antioxidant natural compound that is able to regulate histone epigenetic markers. Nevertheless, additional in vivo studies are required to further investigate the beneficial effects of this EVOO secoiridoid, which might be a promising epinutraceutical bioproduct for the management of immune-related inflammatory diseases.
Immunomodulatory Effects of (R)-Sulforaphane on LPS-Activated Murine Immune Cells: Molecular Signaling Pathways and Epigenetic Changes in Histone Markers
(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Alcarranza Saucedo, Manuel; Villegas Lama, Isabel; Muñoz García, Rocío; Recio Jiménez, Rocío; Fernández Fernández, Inmaculada; Alarcón de la Lastra Romero, Catalina; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
The aim of this study was to explore the immunomodulatory effects of the natural enantiomer (R)-Sulforaphane (SFN) and the possible signaling pathways involved in an ex vivo model of LPS-stimulated murine peritoneal macrophages. Furthermore, we studied the epigenetic changes induced by (R)-SFN as well as the post-translational modifications of histone H3 (H3K9me3 and H3K18ac) in relation to the production of cytokines in murine splenocytes after LPS stimulation. (R)-SFN was able to modulate the inflammatory response and oxidative stress induced by LPS stimulation in murine peritoneal macrophages through the inhibition of reactive oxygen species (ROS), nitric oxide (NO) and cytokine (IL-1β, IL-6, IL-17, IL-18 and TNF-α) production by down-regulating the expression of pro-inflammatory enzymes (iNOS, COX-2 and mPGES-1). We also found that activation of the Nrf-2/HO-1 axis and inhibition of the JAK2/STAT-3, MAPK, canonical and non-canonical inflammasome signaling pathways could have been responsible for the immunomodulatory effects of (R)-SFN. Furthermore, (R)-SFN modulated epigenetic modifications through histone methylation (H3K9me3) and deacetylation (H3K18ac) in LPS-activated spleen cells. Collectively, our results suggest that (R)-SFN could be a promising epinutraceutical compound for the management of immunoinflammatory diseases.
Innovación docente de la asignatura optativa “Fitoterapia” en el Grado en Farmacia
(Real e Ilustre Colegio Oficial de Farmacéuticos, 2023-07) Alcarranza Saucedo, Manuel; Ávila Román, Francisco Javier; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla
La Fitoterapia es una ciencia multidisciplinar que combina conocimientos de diversas áreas. Esta asignatura se imparte en el último curso y ayuda a consolidar los conocimientos adquiridos por el alumno durante la carrera para su vida profesional como farmacéutico. Fitoterapia es una materia optativa que se recupera en el primer cuatrimestre del quinto año del Grado en Farmacia de la Universidad de Sevilla para el curso 2023/2024. El objetivo de esta disciplina es proporcionar al alumnado el conocimiento necesario sobre plantas medicinales y recursos bibliográficos científicos, necesarios para su carrera profesional. La metodología se centrará en las prácticas, que se repartirán en 5 días no consecutivos de 3 horas presenciales cada uno. El primer día, se realizará una excursión al campo para el reconocimiento de plantas medicinales silvestres. El segundo día, se formará al alumnado en la utilización del gestor bibliográfico Mendeley y el uso de bases de datos científicas. El tercer día, se trabajará en el laboratorio para determinar y analizar una droga asignada al azar. Los resultados obtenidos se emplearán para redactar una memoria evaluable en el periodo comprendido entre los días 4 y 5. El día 5, los alumnos expondrán sus resultados oralmente ante la clase. La evaluación del módulo de prácticas se basará en los 1,5 créditos asignados: 70% de la nota corresponderá a la memoria escrita, 20% a la presentación oral y 10% a la realización de actividades dirigidas. Los trabajos más destacados se presentarán en las Jornadas de Fitoterapia mediante un póster, donde se expondrá la investigación realizada y será valorado positivamente en la calificación final de la asignatura. Los conocimientos adquiridos serán de utilidad para el futuro profesional: elaboración de fórmulas magistrales, recomendación de productos naturales en la oficina de farmacia o desarrollo profesional en la industria (departamentos de I+D+i y calidad).
(R)-8-Methylsulfinyloctyl isothiocyanate from Nasturtium officinale inhibits LPS-induced immunoinflammatory responses in mouse peritoneal macrophages: chemical synthesis and molecular signaling pathways involved
(Royal Society of Chemistry, 2023-07-20) Alcarranza Saucedo, Manuel; Villegas Lama, Isabel; Recio Jiménez, Rocío; Muñoz García, Rocío; Fernández Fernández, Inmaculada; Alarcón de la Lastra Romero, Catalina; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía; Universidad de Sevilla. FQM102: Estereoquímica y Síntesis Asimétrica; Universidad de Sevilla. CTS259: Farmacología Experimental y Farmacia Clínica
The aim of this study was to develop an optimal synthetic route to obtain natural (R)-8-methylsulfinyloctyl isothiocyanate ((R)-8-OITC), present in watercress, based on the “DAG methodology” as well as to evaluate its potential antioxidant and immunomodulatory effects, exploring possible signaling pathways that could be involved in an ex vivo model of murine peritoneal macrophages stimulated with LPS. Treatment with (R)-8-OITC inhibited the levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-17 and IL-18), intracellular ROS production and expression of pro-inflammatory enzymes (COX-2, iNOS and mPGES-1) through modulation of the expression of Nrf2, MAPKs (p38, JNK and ERK) and JAK/STAT, and the canonical and non-canonical pathways of the inflammasome. Taking all these together, our results provide a rapid and cost-effective synthetic route to obtain natural (R)-8-OITC and demonstrate that it could be a potential nutraceutical candidate for managing immuno-inflammatory pathologies. Therefore, further in vivo trials are warranted.

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Examinando Farmacología por Autor "Alcarranza Saucedo, Manuel"