Búsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae)
ilustraciones, fotografías, gráficas, tablas
- Autores:
-
Bustamante Romero, Andrés Felipe
- Tipo de recurso:
- Fecha de publicación:
- 2022
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/81720
- Palabra clave:
- 610 - Medicina y salud::615 - Farmacología y terapéutica
Zanthoxylum
Zanthoxylum
Enfermedad de Alzheimer/tratamiento farmacológico
Fármacos Neuroprotectores
Alzheimer Disease/drug therapy
Neuroprotective Agents
Enfermedad de Alzheimer
Zanthoxylum caribaeum
Aislamiento químico biodirigido
LXR
Multifuncional
Alzheimer's disease
Bio-guided chemical isolation
Multifunctional
- Rights
- openAccess
- License
- Atribución-NoComercial-SinDerivadas 4.0 Internacional
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Universidad Nacional de Colombia |
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| dc.title.spa.fl_str_mv |
Búsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae) |
| dc.title.translated.eng.fl_str_mv |
Search for active principles with neuroprotective potential for the treatment of alzheimer's disease from a species of the gender Zanthoxylum caribaeum (Rutaceae) |
| title |
Búsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae) |
| spellingShingle |
Búsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae) 610 - Medicina y salud::615 - Farmacología y terapéutica Zanthoxylum Zanthoxylum Enfermedad de Alzheimer/tratamiento farmacológico Fármacos Neuroprotectores Alzheimer Disease/drug therapy Neuroprotective Agents Enfermedad de Alzheimer Zanthoxylum caribaeum Aislamiento químico biodirigido LXR Multifuncional Alzheimer's disease Bio-guided chemical isolation Multifunctional |
| title_short |
Búsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae) |
| title_full |
Búsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae) |
| title_fullStr |
Búsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae) |
| title_full_unstemmed |
Búsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae) |
| title_sort |
Búsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae) |
| dc.creator.fl_str_mv |
Bustamante Romero, Andrés Felipe |
| dc.contributor.advisor.spa.fl_str_mv |
Ávila Murillo, Mónica Constanza Sandoval Hernández, Adrián Gabriel |
| dc.contributor.author.spa.fl_str_mv |
Bustamante Romero, Andrés Felipe |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de Investigación en Química de Productos Naturales Vegetales Bioactivos (Quipronab) |
| dc.subject.ddc.spa.fl_str_mv |
610 - Medicina y salud::615 - Farmacología y terapéutica |
| topic |
610 - Medicina y salud::615 - Farmacología y terapéutica Zanthoxylum Zanthoxylum Enfermedad de Alzheimer/tratamiento farmacológico Fármacos Neuroprotectores Alzheimer Disease/drug therapy Neuroprotective Agents Enfermedad de Alzheimer Zanthoxylum caribaeum Aislamiento químico biodirigido LXR Multifuncional Alzheimer's disease Bio-guided chemical isolation Multifunctional |
| dc.subject.agrovoc.spa.fl_str_mv |
Zanthoxylum |
| dc.subject.agrovoc.eng.fl_str_mv |
Zanthoxylum |
| dc.subject.decs.spa.fl_str_mv |
Enfermedad de Alzheimer/tratamiento farmacológico Fármacos Neuroprotectores |
| dc.subject.decs.eng.fl_str_mv |
Alzheimer Disease/drug therapy Neuroprotective Agents |
| dc.subject.proposal.spa.fl_str_mv |
Enfermedad de Alzheimer Zanthoxylum caribaeum Aislamiento químico biodirigido LXR Multifuncional |
| dc.subject.proposal.eng.fl_str_mv |
Alzheimer's disease Bio-guided chemical isolation Multifunctional |
| description |
ilustraciones, fotografías, gráficas, tablas |
| publishDate |
2022 |
| dc.date.accessioned.none.fl_str_mv |
2022-07-19T22:41:59Z |
| dc.date.available.none.fl_str_mv |
2022-07-19T22:41:59Z |
| dc.date.issued.none.fl_str_mv |
2022-06-08 |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/masterThesis |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
| dc.type.content.spa.fl_str_mv |
Text |
| dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/TM |
| status_str |
acceptedVersion |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/81720 |
| dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
| dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
| dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.unal.edu.co/ |
| url |
https://repositorio.unal.edu.co/handle/unal/81720 https://repositorio.unal.edu.co/ |
| identifier_str_mv |
Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
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spa |
| language |
spa |
| dc.relation.indexed.spa.fl_str_mv |
Bireme |
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Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Ávila Murillo, Mónica Constanzad26839373d12f4b4932a0ceebaaf03b1600Sandoval Hernández, Adrián Gabriel2bd70ff6a3a7af73c5e7d7ef2dceb9f0600Bustamante Romero, Andrés Felipee9d69122e894e8de7287a64df77df3c9Grupo de Investigación en Química de Productos Naturales Vegetales Bioactivos (Quipronab)2022-07-19T22:41:59Z2022-07-19T22:41:59Z2022-06-08https://repositorio.unal.edu.co/handle/unal/81720Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, fotografías, gráficas, tablasLa Enfermedad de Alzheimer (EA) es la demencia más común, un desorden neurodegenerativo de carácter multifactorial caracterizado por la presencia de placas amiloides, ovillos neurofibrilares, reducción de la actividad colinesterasa, estrés oxidativo, entre otros mecanismos. A pesar de la inversión en investigación durante las últimas décadas, se considera que la investigación debe tomar nuevos enfoques, buscar nuevas dianas biológicas y desarrollar nuevos fármacos, es por ello que en este trabajo se realiza la búsqueda y caracterización de compuestos con actividad multi-diana a partir de productos naturales, teniendo en cuenta que estudios previos de los grupos de investigación demostraron la actividad biológica y el potencial neuroprotector de especies de la familia Rutaceae y particularmente las pertenecientes al género Zanthoxylum de la flora colombiana, las cuales poseen efectos antioxidantes, agonista de LXR e inhibidores de colinesterasas. El objetivo de este trabajo fue realizar una búsqueda de agentes neuroprotectores a partir de la especie Z. caribaeum. Inicialmente se obtuvo un extracto mediante maceración etanólica en frio de la raíz, posteriormente se determinaron el tipo de metabolitos presentes usando técnicas de coloración, se fraccionó el extracto usando cromatografía liquida al vacío (CLV), los compuestos se purificaron usando técnicas cromatográficas, se identificó la estructura química de los compuestos mediante técnicas espectroscópicas y espectrométricas, se evaluó la capacidad antioxidante mediante el método DPPH, y protección del foto-blanqueo del β-caroteno, se evaluó la actividad inhibitoria de acetil y butiril colinestearasas mediante el método Ellman, se realizaron ensayos de viabilidad celular y neuro-protección por MTT, se evaluó la actividad agonista de LXR mediante el ensayo del gen reportero y se determinó la capacidad antiagregante de Aβ de los compuestos mediante un modelo in vitro de cinética de agregación del péptido amiloide. Dentro de los resultados, se logró determinar en el extracto la presencia de metabolitos de tipo alcaloidal, fenólicos, aminas, entre otros. Tanto el extracto como algunas fracciones obtenidas, presentaron actividad agonista de LXR, actividad captadora de radicales libres, protección frente a la peroxidación lipídica y actividad inhibitoria de la butiril colinesterasa; de estas fracciones y mediante el aislamiento químico dirigido, se obtuvo el compuesto 10H-furano [3,2-a] carbazol, el compuesto 5,7 -dimetoxi-4H-cromen-4-ona, y una mezcla de esteroles que contiene estigmasterol y β-sitosterol. El compuesto 10H-furano [3,2-a] carbazol presentó actividad agonista de LXR, se observó efecto neuroprotector y actividad antiagregante de Aβ; el compuesto 5,7 -dimetoxi-4H-cromen-4-ona se reporta por primera vez en esta especie, presenta efecto neuroprotector y actividad antiagregante de Aβ; por su parte, la mezcla de esteroles estigmasterol y β-sitosterol presentó actividad agonista de LXR, efecto neuroprotector y actividad antiagregante de Aβ. Nuestros resultados nos permiten concluir que tanto las fracciones y compuestos aislados de Z. caribaeum presentan un potencial multifuncional para la terapéutica de la EA. (Texto tomado de la fuente).Alzheimer's Disease (AD) is the most common dementia, a multifactorial neurodegenerative disorder characterized by the accumulation of amyloid plaques, neurofibrillary tangles, reduced cholinesterase activity, oxidative stress, among other mechanisms. Despite the investment in research during the last decades, it is considered that research must take new approaches, search for new biological targets and develop new drugs. Here we carry out the search and characterization of compounds with multi-functional activity from Ethanolic extract of Z.caribaeum roots. Previous studies of our research groups demonstrated the biological activity and neuroprotective potential of species of the Rutaceae family and particularly those belonging to the Zanthoxylum genus, which have antioxidant effects, LXR agonist activity and cholinesterase inhibitors. The aim of this work was the search for neuroprotective agents from Zanthoxylum caribaeum. Ethanolic extract of Z.caribaeum roots, was obtained by maceration. The kind of metabolites presents in the extract were determined using coloration assays, the fractionation was carried out using vacuum liquid chromatography (VLC). The compounds were purified by chromatographic techniques, the chemical structures were identified by spectroscopic and spectrometric techniques. The multifunctional potential of ethanolic extract roots, and fractions was determined by antioxidant capacity (DPPH method, and protection from photo-bleaching of β-carotene), inhibitory activity of cholinesterases (acetyl and butyryl cholinesterases), and LXR agonist effect (the gene-reporter assay). In the extract was detected the presence of alkaloidal, phenolic, amines metabolites. The extract and some fractions have LXR agonist activity, free radical scavenging activity, protection against lipid peroxidation, and butyryl cholinesterase inhibitory activity. The compound 10H-furan[3,2-a]carbazole, 5,7-dimethoxy-4H-chromen-4-one, and a mixture of sterols containing stigmasterol and β-sitosterol were isolated and this multifuntional potential was determined by the LXR agonistic activity, Neuroprotective and the Aβ antiaggregating capacity in model in vitro of amyloid peptide aggregation kinetics The compound 10H-furan [3,2-a] carbazole showed LXR agonist activity, neuroprotective effect and antiaggregant activity of Aβ; the compound 5,7-dimethoxy-4H-chromen-4-one is reported for the first time in this species and has a neuroprotective effect and antiaggregant activity of Aβ. Stigmasterol and β-sitosterol presented LXR agonist activity, neuroprotective effect and Aβ antiaggregant activity. Our results allow us to conclude that both the fractions and compounds isolated from Z. caribaeum have multifunctional potential for therapeutics in AD.MaestríaMagíster en NeurocienciasNeurofarmacologíaxxiii, 138 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en NeurocienciasFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::615 - Farmacología y terapéuticaZanthoxylumZanthoxylumEnfermedad de Alzheimer/tratamiento farmacológicoFármacos NeuroprotectoresAlzheimer Disease/drug therapyNeuroprotective AgentsEnfermedad de AlzheimerZanthoxylum caribaeumAislamiento químico biodirigidoLXRMultifuncionalAlzheimer's diseaseBio-guided chemical isolationMultifunctionalBúsqueda de principios activos con potencial neuroprotector para el tratamiento de la enfermedad de alzheimer a partir de una especie del género Zanthoxylum caribaeum (Rutaceae)Search for active principles with neuroprotective potential for the treatment of alzheimer's disease from a species of the gender Zanthoxylum caribaeum (Rutaceae)Trabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMBiremeAddae‐Mensah, I., Munenge, R., & Guantai, A. 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Acta Pharmacologica Sinica, 33(9), 1170–1175. https://doi.org/10.1038/aps.2012.128EstudiantesInvestigadoresPúblico generalORIGINALDOC TESIS AFBR VF 2022.pdfDOC TESIS AFBR VF 2022.pdfTesis de Maestría en Neurocienciasapplication/pdf3309136https://repositorio.unal.edu.co/bitstream/unal/81720/5/DOC%20TESIS%20AFBR%20VF%202022.pdf585ff3cc5327ef869f4f08c2cf0db746MD55LICENSElicense.txtlicense.txttext/plain; charset=utf-84074https://repositorio.unal.edu.co/bitstream/unal/81720/4/license.txt8153f7789df02f0a4c9e079953658ab2MD54THUMBNAILDOC TESIS AFBR VF 2022.pdf.jpgDOC TESIS AFBR VF 2022.pdf.jpgGenerated Thumbnailimage/jpeg6686https://repositorio.unal.edu.co/bitstream/unal/81720/6/DOC%20TESIS%20AFBR%20VF%202022.pdf.jpgb4c3aa207b9184e4bf5d735126322130MD56unal/81720oai:repositorio.unal.edu.co:unal/817202023-08-05 23:04:19.203Repositorio Institucional Universidad Nacional de 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