Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acción

96 páginas : gráficas

Autores:
Núñez Márquez, Jeidy Marlin
Escobar Romero, Yandi Yashana
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2019
Institución:
Universidad de Ciencias Aplicadas y Ambientales U.D.C.A
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Repositorio Institucional UDCA
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spa
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oai:repository.udca.edu.co:11158/1924
Acceso en línea:
https://repository.udca.edu.co/handle/11158/1924
Palabra clave:
Análisis químico de las plantas
Campánula
Diterpenos
Campánula
Extractos vegetales
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repository_id_str
dc.title.spa.fl_str_mv Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acción
title Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acción
spellingShingle Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acción
Análisis químico de las plantas
Campánula
Diterpenos
Campánula
Extractos vegetales
title_short Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acción
title_full Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acción
title_fullStr Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acción
title_full_unstemmed Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acción
title_sort Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acción
dc.creator.fl_str_mv Núñez Márquez, Jeidy Marlin
Escobar Romero, Yandi Yashana
dc.contributor.advisor.spa.fl_str_mv Estrada Semprun, Omar, dir.
Urrego Novoa, José Ricardo, dir.
dc.contributor.author.spa.fl_str_mv Núñez Márquez, Jeidy Marlin
Escobar Romero, Yandi Yashana
dc.subject.lemb.spa.fl_str_mv Análisis químico de las plantas
topic Análisis químico de las plantas
Campánula
Diterpenos
Campánula
Extractos vegetales
dc.subject.proposal.spa.fl_str_mv Campánula
Diterpenos
dc.subject.agrovoc.spa.fl_str_mv Campánula
Extractos vegetales
description 96 páginas : gráficas
publishDate 2019
dc.date.accessioned.spa.fl_str_mv 2019-08-06T22:10:10Z
dc.date.available.spa.fl_str_mv 2019-08-06T22:10:10Z
dc.date.issued.spa.fl_str_mv 2019
dc.type.spa.fl_str_mv Trabajo de grado - Pregrado
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dc.identifier.local.spa.fl_str_mv QF033 N85e 2019 (205606)
url https://repository.udca.edu.co/handle/11158/1924
identifier_str_mv QF033 N85e 2019 (205606)
dc.language.iso.spa.fl_str_mv spa
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spelling Estrada Semprun, Omar, dir.Urrego Novoa, José Ricardo, dir.Núñez Márquez, Jeidy MarlinEscobar Romero, Yandi Yashana2019-08-06T22:10:10Z2019-08-06T22:10:10Z2019https://repository.udca.edu.co/handle/11158/1924QF033 N85e 2019 (205606)96 páginas : gráficasCardiovascular disease is a health problem worldwide. In Colombia, there is a 45% prevalence of hypertension, associated complications such as heart failure, coronary ischemia multifactorial where the risk factor is one of the highest of Latin American countries. The use of pharmacological treatments has been shown to reduce morbidity and mortality from cardiovascular disease, reducing complications associated with hypertension. For this reason today the search for new alternatives continues with antihypertensive potential; in these order natural products as a source for obtaining biological active molecules are explored. Previous studies have shown that members of the bellflower family have potentially beneficial cardiovascular level activities with antioxidant and / or anti-inflammatory. Therefore the aim of this study was to evaluate the vasorelaxant effect of medium C. in an assay by bioassay-guided technique isolated organ in rat aortic rings, characterize the compound of greater activity and suggest a possible mechanism of action.(He et al., 2014) The results showed that the hydroalcoholic extract of Campanula medium CmXO had two compounds vasorelaxant effect endothelium-dependent. Solubility by a method of solvent and column chromatography and Sephadex LH-20 reverse phase RP18 was achieved isolate two compounds; an already known and reported in the literature as routine and a diterpene named by us as CmE1B, the latter the largest vasorelaxant activity. This compound was characterized qualitatively by thin layer chromatography and then analyzed by NMR and H-1 and C-13 NMR was determined that a diterpene type labdane dihydroxyl. By isolated organ technique it determined that CmE1B has an endothelium-dependent vasorelaxant activity, acting primarily via the nitric oxide and cGMP and through the activation of K + channels dependent Ca2 + in endothelial cellsLas enfermedades cardiovasculares son un problema de salud a nivel mundial. En Colombia existe una prevalencia de 22,82% de hipertensión arterial, según la encuesta Nacional de Salud-2007, asociado a complicaciones como insuficiencia cardiaca, isquemia coronaria de origen multifactorial donde el factor de riesgo es uno de los más altos de los países latinoamericanos (Salud, 2017). El uso de tratamientos farmacológicos ha demostrado reducir la morbilidad y mortalidad por enfermedades cardiovasculares, disminuyendo complicaciones asociadas a la hipertensión. Por esta razón en la actualidad se continúa la búsqueda de nuevas alternativas con potencial antihipertensivo; en este orden se exploran los productos naturales como fuente de obtención de moléculas con actividad biológica. Estudios previos han demostrado que miembros de la familia Campanulaceae poseen actividades potencialmente benéficas a nivel cardiovascular con efectos antioxidantes y/o antiinflamatorios (He et al., 2014). Por esto el objetivo de este estudio fue evaluar el efecto vasorelajante de C. medium, en un ensayo biodirigido mediante la técnica de órgano aislado en anillos aórticos de rata, caracterizar el compuesto de mayor actividad y proponer un posible mecanismo de acción. Los resultados demostraron que el extracto etanólico de Campanula medium CmXO poseía dos compuestos con efecto vasorelajante endotelio-dependiente. Mediante un método de solubilidad por solvente y cromatografía de columna Sephadex LH-20 y fase reversa RP18 se logró aislar dos compuestos; uno ya conocido y reportado en la literatura como rutina y un diterpeno nombrado por nosotros como CmE1B, este último el de mayor actividad vasorelajante. Este compuesto fue caracterizado cualitativamente por cromatografía de capa fina y posteriormente analizado por y RMN H-1 y RMN C-13 determinándose que era un diterpeno tipo labdano dihidroxilado. Mediante la técnica de órgano aislado se determinó que CmE1B tiene una actividad vasorelajante dependiente de endotelio, que actúa mayoritariamente por la vía del óxido nítrico y GMPc y a través de la activación de canales de K+ dependientes de Ca2+ en las células endotelialesIncluye bibliografíaPregradoQuímico(a) Farmacéuticoapplication/pdfspaBogotá : Universidad de Ciencias Aplicadas y Ambientales, 2019Facultad de CienciasQuímica FarmacéuticaDerechos Reservados - Universidad de Ciencias Aplicadas y Ambientaleshttps://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_abf2Estudio de efecto vasorelajante del extracto etanólico Campanula medium aislamiento biodirigido del compuesto activo y posible mecanismo de acciónTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/publishedVersionTexthttp://purl.org/redcol/resource_type/TPhttp://purl.org/coar/version/c_970fb48d4fbd8a85Análisis químico de las plantasCampánulaDiterpenosCampánulaExtractos vegetalesAguilar, E. 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AISLAMIENTO BIODIRIGIDO.pdf.jpgGenerated Thumbnailimage/jpeg4379https://repository.udca.edu.co/bitstreams/84dac7fe-11c4-41dd-9933-4edef27a6a18/downloadcd90cb98a46d347ba78f3af1134e8c18MD55ANEXOS.pdf.jpgANEXOS.pdf.jpgGenerated Thumbnailimage/jpeg5780https://repository.udca.edu.co/bitstreams/aedf4e54-5eda-4621-8789-e26a057e645a/download6c61139054869977e83b4e40daaff04aMD5711158/1924oai:repository.udca.edu.co:11158/19242024-05-09 14:34:42.034https://creativecommons.org/licenses/by-nc-sa/4.0/Derechos Reservados - Universidad de Ciencias Aplicadas y Ambientalesopen.accesshttps://repository.udca.edu.coRepositorio - Universidad de Ciencias Aplicadas y Ambientales 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en las Obras Colectivas;
b.	Distribuir copias o fonogramas de las Obras, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública, incluyéndolas como incorporadas en Obras Colectivas, según corresponda;
c.	Distribuir copias de las Obras Derivadas que se generen, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública.
Los derechos mencionados anteriormente pueden ser ejercidos en todos los medios y formatos, actualmente conocidos o que se inventen en el futuro. Los derechos antes mencionados incluyen el derecho a realizar dichas modificaciones en la medida que sean técnicamente necesarias para ejercer los derechos en otro medio o formatos, pero de otra manera usted no está autorizado para realizar obras derivadas.Todos los derechos no otorgados expresamente por el Licenciante quedan por este medio reservados, incluyendo pero sin limitarse a aquellos que se mencionan en las secciones 4(d) y 4(e).
4. Restricciones.
La licencia otorgada en la anterior Sección 3 está expresamente sujeta y limitada por las siguientes restricciones:
a.	Usted puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra sólo bajo las condiciones de esta Licencia, y Usted debe incluir una copia de esta licencia o del Identificador Universal de Recursos de la misma con cada copia de la Obra que distribuya, exhiba públicamente, ejecute públicamente o ponga a disposición pública. No es posible ofrecer o imponer ninguna condición sobre la Obra que altere o limite las condiciones de esta Licencia o el ejercicio de los derechos de los destinatarios otorgados en este documento. No es posible sublicenciar la Obra. Usted debe mantener intactos todos los avisos que hagan referencia a esta Licencia y a la cláusula de limitación de garantías. Usted no puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra con alguna medida tecnológica que controle el acceso o la utilización de ella de una forma que sea inconsistente con las condiciones de esta Licencia. Lo anterior se aplica a la Obra incorporada a una Obra Colectiva, pero esto no exige que la Obra Colectiva aparte de la obra misma quede sujeta a las condiciones de esta Licencia. Si Usted crea una Obra Colectiva, previo aviso de cualquier Licenciante debe, en la medida de lo posible, eliminar de la Obra Colectiva cualquier referencia a dicho Licenciante o al Autor Original, según lo solicitado por el Licenciante y conforme lo exige la cláusula 4(c).
b.	Usted no puede ejercer ninguno de los derechos que le han sido otorgados en la Sección 3 precedente de modo que estén principalmente destinados o directamente dirigidos a conseguir un provecho comercial o una compensación monetaria privada. El intercambio de la Obra por otras obras protegidas por derechos de autor, ya sea a través de un sistema para compartir archivos digitales (digital file-sharing) o de cualquier otra manera no será considerado como estar destinado principalmente o dirigido directamente a conseguir un provecho comercial o una compensación monetaria privada, siempre que no se realice un pago mediante una compensación monetaria en relación con el intercambio de obras protegidas por el derecho de autor.
c.	Si usted distribuye, exhibe públicamente, ejecuta públicamente o ejecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.
d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:
i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.
ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.
e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, Acinpro), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.
5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
7. Término.
a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.
b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.
8. Varios.
a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.
b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.
c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.
d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.

