Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer

ilustraciones, gráficas

Autores:
Ruiz González, Juan Carlos
Tipo de recurso:
Fecha de publicación:
2021
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/80378
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/80378
https://repositorio.unal.edu.co/
Palabra clave:
570 - Biología::572 - Bioquímica
Sapindales
Rutaceae
Alzheimer Disease
Therapeutics
Enfermedad de Alzheimer
Terapéutica
Enfermedad de Alzheimer
Productos naturales vegetales
LXR
Alzheimer's disease
Natural vegetal products
ApoE
Zanthoxylum caribaeum
Rights
openAccess
License
Atribución-NoComercial-CompartirIgual 4.0 Internacional
id UNACIONAL2_4c2cf2ad4c22ee01af64ea6d0c18f14c
oai_identifier_str oai:repositorio.unal.edu.co:unal/80378
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer
dc.title.translated.eng.fl_str_mv Therapeutic potential of Zanthoxylum caribaeum root extract in the triple-transgenic mice model of Alzheimer´s disease
title Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer
spellingShingle Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer
570 - Biología::572 - Bioquímica
Sapindales
Rutaceae
Alzheimer Disease
Therapeutics
Enfermedad de Alzheimer
Terapéutica
Enfermedad de Alzheimer
Productos naturales vegetales
LXR
Alzheimer's disease
Natural vegetal products
ApoE
Zanthoxylum caribaeum
title_short Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer
title_full Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer
title_fullStr Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer
title_full_unstemmed Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer
title_sort Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer
dc.creator.fl_str_mv Ruiz González, Juan Carlos
dc.contributor.advisor.none.fl_str_mv Sandoval-Hernandez, Adrián Gabriel
dc.contributor.author.none.fl_str_mv Ruiz González, Juan Carlos
dc.contributor.researchgroup.spa.fl_str_mv Muerte Celular
dc.subject.ddc.spa.fl_str_mv 570 - Biología::572 - Bioquímica
topic 570 - Biología::572 - Bioquímica
Sapindales
Rutaceae
Alzheimer Disease
Therapeutics
Enfermedad de Alzheimer
Terapéutica
Enfermedad de Alzheimer
Productos naturales vegetales
LXR
Alzheimer's disease
Natural vegetal products
ApoE
Zanthoxylum caribaeum
dc.subject.other.none.fl_str_mv Sapindales
Rutaceae
dc.subject.decs.eng.fl_str_mv Alzheimer Disease
Therapeutics
dc.subject.decs.spa.fl_str_mv Enfermedad de Alzheimer
Terapéutica
dc.subject.proposal.spa.fl_str_mv Enfermedad de Alzheimer
Productos naturales vegetales
dc.subject.proposal.eng.fl_str_mv LXR
Alzheimer's disease
Natural vegetal products
dc.subject.proposal.none.fl_str_mv ApoE
Zanthoxylum caribaeum
description ilustraciones, gráficas
publishDate 2021
dc.date.accessioned.none.fl_str_mv 2021-10-04T21:04:54Z
dc.date.available.none.fl_str_mv 2021-10-04T21:04:54Z
dc.date.issued.none.fl_str_mv 2021-06-29
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/80378
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/80378
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
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spelling Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Sandoval-Hernandez, Adrián Gabriel2bd70ff6a3a7af73c5e7d7ef2dceb9f0600Ruiz González, Juan Carloscd5ab31c63374fc5c3fd98dca56b9d19Muerte Celular2021-10-04T21:04:54Z2021-10-04T21:04:54Z2021-06-29https://repositorio.unal.edu.co/handle/unal/80378Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, gráficasLa Enfermedad de Alzheimer (EA) es la principal causa de demencia en el mundo, se proyecta como el mayor problema de salud pública en el mundo para el año 2050. Su etiología es desconocida, se caracteriza por la pérdida progresiva de la memoria y patológicamente por la acumulación de péptidos beta-amiloide (Aβ) y la proteína Tau-hiperfosforilada. La hipótesis amiloide es la más aceptada, postula que el origen de la enfermedad comienza con la acumulación de Aβ, conlleva a procesos inflamatorios, desregulación de quinasas, incremento de especies reactivas de oxígeno, reducción de células madre neuronales, perdida de espinas dendríticas y muerte neuronal, explicando la demencia. Se ha evidenciado que la activación farmacológica de los receptores X hepáticos (LXR) en modelos animales de EA ha producido mejoría cognitiva asociada con incremento de expresión de las proteínas APOE y ABCA1, reducción de astrogliosis y microgliosis, protección de la plasticidad sináptica y espinas dendríticas. Los productos naturales vegetales han representado una fuente promisoria de moléculas bioactivas de características multimodales para el tratamiento de la EA, debido a sus altas cantidades de compuestos alcaloidales. Por su parte, Zanthoxylum caribaeum es una especie arbórea perteneciente a la familia Rutaceae que ha sido seleccionada luego de un amplio screening de plantas colombianas por su alto contenido de alcaloides, actividad agonista de LXRs, antiagregante de Aβ, antioxidante e inhibidora de acetilcolinesterasas in vitro. El objetivo de este trabajo fue de evaluar el efecto de un extracto etanolico de Zanthoxylum caribeum en un modelo in vivo de EA. Se realizó la administración oral a ratones triple-transgenicos de EA (3xTg-AD) y controles, encontrando mejoría de la memoria espacial en el laberinto acuático de Morris, incremento en la expresión de ABCA1 y ApoE, reducción del marcaje para marcadores moleculares de progresión de la EA. Adicionalmente, se observó un incremento en la expresión de proteínas asociadas con la función sináptica Sinapsina1, Shank 1/2/3 y PSD-95. En conclusión, se describió el efecto de un extracto etanólico crudo de Zanthoxylum caribaeum sobre los principales marcadores fisiopatológicos de la EA con potencial uso terapéutico en el modelo 3xTg-AD. (Texto tomado de la fuente).Alzheimer's disease (AD) is the main cause of dementia worldwide, it is projected as the largest public health problem in the world by the year 2050. Its etiology is unknown, it is characterized by progressive memory loss and pathologically by the accumulation of beta-amyloid peptides (Aβ) and the hyperphosphorylated Tau protein. The amyloid hypothesis is the most accepted, it postulates that the origin of the disease begins with the accumulation of Aβ, which leads to inflammatory processes, dysregulation of kinases, increase in reactive oxygen species, reduction of neuronal stem cells, loss of dendritic spines and death. neuronal, explaining dementia. It has been shown that the pharmacological activation of hepatic X receptors (LXR) in animal models of AD has produced cognitive improvement associated with increased expression of APOE and ABCA1 proteins, reduction of astrogliosis and microgliosis, protection of synaptic plasticity and dendritic spines. Natural products derived from plants have represented a promising source of bioactive molecules with multimodal characteristics for the treatment of AD, due to their high amounts of alkaloidal compounds. Zanthoxylum caribaeum is an arboreal species belonging to the Rutaceae family that has been selected after an extensive screening of Colombian plants for its high alkaloid content, LXRs agonist activity, Aβ antiaggregant, antioxidant and inhibitor of acetylcholinesterase in vitro. The objective of this work is to evaluate the effect of an ethanolic extract of Zanthoxylum caribaeum in the triple transgenic model of Alzheimer´s disease (3xTg-AD). Oral administration to triple-transgenic EA (3xTg-AD) mice and controls was performed, finding improvement in spatial memory in the Morris water maze, increased expression of ABCA1 and ApoE, reduction of expression for molecular markers of progression of the EA. Additionally, an increase in the expression of proteins associated with the synaptic function Synapsin1, Shank 1/2/3 and PSD-95 was observed. In conclusion, the effect of a crude ethanolic extract of Zanthoxylum caribaeum on the main pathophysiological markers of AD with potential therapeutic use in the 3xTg-AD model was described.proyecto: “Búsqueda racional de alcaloides isoquinolínicos del género Zanthoxylum (Rutaceae) como posibles agentes neuroprotectores para el tratamiento de la enfermedad de Alzheimer" Código 110177758004, convocatoria 777-2017" -RC-854 de 2017.MaestríaMagíster en Ciencias - BioquímicaEnfermedades neurodegenerativasxxii, 104 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - BioquímicaDepartamento de QuímicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::572 - BioquímicaSapindalesRutaceaeAlzheimer DiseaseTherapeuticsEnfermedad de AlzheimerTerapéuticaEnfermedad de AlzheimerProductos naturales vegetalesLXRAlzheimer's diseaseNatural vegetal productsApoEZanthoxylum caribaeumEvaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de AlzheimerTherapeutic potential of Zanthoxylum caribaeum root extract in the triple-transgenic mice model of Alzheimer´s diseaseTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAdesina, S. . 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CNS Neurosci Ther., 25(February), 665–673. https://doi.org/10.1111/cns.13123Búsqueda racional de alcaloides isoquinolínicos del género Zanthoxylum (Rutaceae) como posibles agentes neuroprotectores para el tratamiento de la enfermedad de AlzheimerMinisterio de Ciencia, Tecnología e InnovaciónInvestigadoresPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-83964https://repositorio.unal.edu.co/bitstream/unal/80378/1/license.txtcccfe52f796b7c63423298c2d3365fc6MD51ORIGINAL1022375276.2021.pdf1022375276.2021.pdfTesis de Maestría en Ciencias - Bioquímicaapplication/pdf3882073https://repositorio.unal.edu.co/bitstream/unal/80378/3/1022375276.2021.pdfa67760f672b072e45dd57456fd465314MD53THUMBNAIL1022375276.2021.pdf.jpg1022375276.2021.pdf.jpgGenerated Thumbnailimage/jpeg5652https://repositorio.unal.edu.co/bitstream/unal/80378/4/1022375276.2021.pdf.jpgd5dfe383827cb84b61d5430c3831f70bMD54unal/80378oai:repositorio.unal.edu.co:unal/803782024-07-28 23:59:26.31Repositorio Institucional 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