Safety evaluation in healthy Colombian volunteers of P2Et extract obtained from caesalpinia spinosa: Design 3+3 phase I clinical trial

Q3Q2The polyphenol-enriched extract called P2Et derived from Caesalpinia spinosa (C. spinosa) had antitumor and immunomodulatory activities reported in breast cancer, leukemia, and melanoma. The aim of this study was to evaluate the safety and maximum tolerated dose of P2Et extract in Colombian healthy volunteers in a phase 1 clinical trial, open labelled, single-arm, dose-escalation design 3 + 3. Seven healthy volunteers were included; P2Et was administrated in capsules of 600 mg/d for 28 days. Analysis by intention to treat was performed. 4 volunteers showed adverse events and discontinued the intervention. 94.6% of AE were grade 1, and most of AE had a reasonable possibility of a relationship with the P2Et (83.8%). We found that the oral administration of P2Et is safe in healthy humans with a maximum tolerated dose of 600 mg/d. There was no severe toxicity; most of the adverse events were mild, without significant changes in the safety parameters evaluated.https://orcid.org/0000-0001-5133-2206https://orcid.org/0000-0002-8468-8716https://orcid.org/0000-0002-5392-7083https://orcid.org/0000-0002-2478-0908https://orcid.org/0000-0001-5529-8279https://orcid.org/0000-0001-5608-3181https://orcid.org/0000-0002-4664-0682Revista Internacional - IndexadaA1N

A gallotannin-rich fraction from Caesalpinia spinosa (Molina) Kuntze displays cytotoxic activity and raises sensitivity to doxorubicin in a leukemia cell line

<p>Abstract</p> <p>Background</p> <p>Enhancement of tumor cell sensitivity may help facilitate a reduction in drug dosage using conventional chemotherapies. Consequently, it is worthwhile to search for adjuvants with the potential of increasing chemotherapeutic drug effectiveness and improving patient quality of life. Natural products are a very good source of such adjuvants.</p> <p>Methods</p> <p>The biological activity of a fraction enriched in hydrolysable polyphenols (P2Et) obtained from <it>Caesalpinia spinosa </it>was evaluated using the hematopoietic cell line K562. This fraction was tested alone or in combination with the conventional chemotherapeutic drugs doxorubicin, vincristine, etoposide, camptothecin and taxol. The parameters evaluated were mitochondrial depolarization, caspase 3 activation, chromatin condensation and clonogenic activity.</p> <p>Results</p> <p>We found that the P2Et fraction induced mitochondrial depolarization, activated caspase 3, induced chromatin condensation and decreased the clonogenic capacity of the K562 cell line. When the P2Et fraction was used in combination with chemotherapeutic drugs at sub-lethal concentrations, a fourfold reduction in doxorubicin inhibitory concentration 50 (IC₅₀) was seen in the K562 cell line. This finding suggested that P2Et fraction activity is specific for the molecular target of doxorubicin.</p> <p>Conclusions</p> <p>Our results suggest that a natural fraction extracted from <it>Caesalpinia spinosa </it>in combination with conventional chemotherapy in combination with natural products on leukemia cells may increase therapeutic effectiveness in relation to leukemia.</p

A fraction from Petiveria alliacea induces apoptosis via a mitochondria-dependent pathway and regulates HSP70 expression

Una fracción de Petiveria alliacea induce apoptosis dependiente de la mitocondria y regula la expresión de la proteína HSP70. Objetivo: Evaluar la actividad biológica in vitro de extractos de Petiveria alliacea utilizando líneas celulares tumorales. Materiales y Métodos: Las fracciones de P.alliacea fueron preparadas mediante un protocolo de purificación biodirigido. La actividad biológica fue caracterizada utilizando dos líneas celulares tumorales de origen humano, donde se analizaron los cambios morfológicos, la viabilidad celular, la actividad sobre la membrana mitocondrial y la fragmentación nuclear. Asimismo se evaluó la actividad de las fracciones sobre la expresión de la proteína HSP70. Resultados: El presente estudio muestra que las fracciones de P.alliacea inducen muerte celular por apoptosis dependiente de la mitocondria y además regulan negativamente la expresión de la proteína HSP70. Los compuestos que posiblemente son responsables de la actividad biológica presente en las fracciones de P.alliacea fueron identificados por desreplicación. Conclusión: El presente estudio contribuyea explicar en parte las propiedades antitumorales de la planta P.alliacea descritas en diversos escritos etnobotánicos.Palabras claves: apoptosis; cáncer; proteínas de choque térmico; Petiveria alliacea.Abstract Objective: To evaluate the biological activity of Petiveria alliacea extracts on tumoral cells in vitro. Materials and Methods: P.alliacea fractions prepared by a bioguided purification protocol were characterized by their biological activities on two human tumoral cell lines. Morphological changes, cell viability, mitochondrial membrane depolarization, nuclear staining and activity on HSP70 were analyzed. Results: The present study demonstrates that P.alliacea fractions can induce apoptosis in a mitochondria-dependent pathway and down regulate HSP70 expression in vitro. The possible compounds present in P.alliacea responsible for the described biological activities were identified by de-replication methods. Conclusion: The present study provides new knowledge on the antitumoral properties of the plant species P. alliacea described in several ethnobotanical studies.Key words: apoptosis; cancer; heat shock proteins; Petiveria alliacea.ResumoUma fração de Petiveria alliacea induz apoptose dependente da mitocôndria e regula a expressão da proteína HSP70. Objetivo: Avaliar a atividade biológica in vitro de extratos de Petiveria alliacea utilizando linhagens de células tumorais. Materiais e Métodos: Frações de P.alliacea foram preparadas utilizando um protocolo de purificação bio-dirigido. A atividade biológica foi caracterizada utilizando duas linhagens de células tumorais de origem humana, onde se analisaram as alterações morfológicas, a viabilidade celular, a atividade na membrana mitocondrial e a fragmentação nuclear. Também se avaliaram a atividade das frações sobre a expressão da proteína HSP70. Resultados: Este estudo mostra que as frações de P.alliacea induzem a morte celular por apoptose dependente da mitocôndria e também regulam negativamente a expressão da proteína HSP70. Os compostos que provavelmente são responsáveis pela atividade biológica presente nas frações de P.alliacea foram identificados por dereplicação. Conclusão: Este estudo ajuda a explicar, em parte, as propriedades antitumorais da planta P.alliacea descrita em vários escritos etnobotânicosPalavras-chave: apoptose, Câncer, Proteínas de choque térmico; Petiveria alliacea

A fraction from Petiveria alliacea induces apoptosis via a mitochondria-dependent pathway and regulates HSP70 expression

To evaluate the biological activity of Petiveria alliacea extracts on tumoral cells in vitro. Materials and methods. P.alliaceafractions prepared by a bioguided purification protocol were characterized by their biological activities on two human tumoral cell lines.Morphological changes, cell viability, mitochondrial membrane depolarization, nuclear staining and activity on HSP70 were analyzed.Results. The present study demonstrates that P.alliacea fractions can induce apoptosis in a mitochondria-dependent pathway and downregulate HSP70 expression in vitro. The possible compounds present in P.alliacea responsible for the described biological activities wereidentified by dereplication methods. Conclusion. The present study provides new knowledge on the antitumoral properties of the plantspecies P. alliacea described in several ethnobotanical studies

Extractos complejos de caesalpinia spinosa inducen apoptosis en lineas de celulas tumorales.

Caesalpinia spinosa, is a Peruvian perennial tree also distributed in several Colombian regions, and traditionally known as Dividivi. Folk medicine describes the Caesalpinia spinosa as a plant having anti-inflammatory properties. Fruit extracts were obtained by drying the fruits in a solar furnace with natural convection at 35°C. The dried material was percolated with 96% ethanol and extracted with solvents of increasing of polararity. Tumor cell lines viability and morphologic analysis showed that the ethanol, and ethyl acetate extracts and a precipitate obtained from the ethyl acetate extract, a high citotoxic activity at relatively low concentrations. Furthermore, at higher concentrations, changes in the mitochondria membrane potential and apoptotic cells were observed. The bio-guided purification has allow us to obtain in short time a not to complex fraction exhibiting a clear antitumor activity.Caesalpinia espinosa, comunmente denominada Dividivi es un árbol perenne originario del Perú y distribuido en algunas regiones Colombianas. La medicina tradicional describe que Caesalpina espinosa como una planta que tiene propiedades anti-inflamatorioas. Los extractos fueron obtenidos luego de secar la planta fresca en horno solar con convección natural a 35°C. El material seco fue extraído con etanol al 96% por percolación y separado con solventes de polaridad creciente. Los análisis de viabilidad y morfología sobre líneas de células tumorales mostraron que los extractos de etanol, acetato de etilo y un precipitado obtenido del acetato de etilo, presentan una alta actividad citotóxica a una baja concentración. Además se evidenciaron cambios en el potencial de la membrana mitocondrial y aparición de células apoptóticas a una concentración mayor. La purificación biodirigida, nos ha permitido obtener rápidamente una fracción poco compleja y fácil de obtener, que presenta una clara actividad antitumoral

Induccion de apoptosis y detencion en g2 del ciclo celular en celulas tumorales podria explicar la actividad antitumoral de petiveria alliacea.

Petiveria alliacea, is a perennial shrub from the Amazon and other tropical regions of America, traditionally known as Anamu and belongs to the Phytocalacceae family. It has been reported that its roots and leaves have analgesic, antifungal properties. as well as immunoregulatory activity. The ethyl acetate extract fractions purified through RP-18 column show diverse biological activities. Fractions F1, F2 and F4 exhibits low activity at the higher concentrations tested (250 to 62.5 mg/ml), while fraction F4 at low concentrations induces cell cycle G2 arrest. Fractions have been characterized by HPLC-UV and at present, the HPLC-MS analysis are being carry out to determine the chemical nature of the fraction components.Petiveria alliacea, es un arbusto perenne presente en la selva amazónica y otras regiones tropicales de America, tradicionalmente conocida como Anamu y perteneciente a la familia phytolacceae. Reportes muestran que las raices y hojas tiene propiedades analgésicas y antifúngicas. Sin embargo, la planta ha sido reconocida por su actividad inmunoreguladora. Las fracciones obtenidas en Acetato de etilo, purificado por columna RP18, muestran diferentes tipos de actividades biológicas. Las fracciones F1, F2 y F4 muestran una débil actividad a altas concentraciones (250 a 62.5 mg/ml), mientras que a bajas concentraciones, la fracción F4 induce detención del ciclo celular en la fase G2. Cada una de estas fracciones ha sido caracterizada por HPLC-UV con lector de diodos y actualmente se esta realizando el análisis por HPLC-MS para determinar la naturaleza de cada una de los componentes de esta fracción

Problemática en la búsqueda y ubicación de victimas de desaparición forzada, en el departamento del Guaviare

El delito de desaparición forzada en Colombia se encuentra tipificado en el artículo 165 del Código penal en el Título III del capítulo Primero “Delitos contra la Libertad Individual y otras garantías” siendo catalogada con el trascurrir del tiempo, como un crimen de Estado. Ha sido un hecho notorio que ha afectado cantidades de hogares Colombianos; desvertebrando así a familias enteras , entre ellos padres, esposos, madres, hijos, abuelos, sobrinos, primos, tíos, suegros, cuñados, etc., impidiendo cumplir sus expectativas y proyectos de vida en conjunto a su grupo familiar. Según consultas realizadas respecto al delito de desaparición forzada en Colombia existe un sinnúmero de definiciones, análisis , investigaciones , artículos periodísticos, informes, libros, folletos, guías, etc., mostrando su evolución histórica a nivel internacional y nacional, sus características, clases de responsables de este crimen de lesa humanidad, tipos de sanciones del mismo, encaminado al avance e inclusión del ordenamiento jurídico colombiano e instrumentos internacionales, sin embargo frente a la parte humanitaria de la reparación del daño consistente en la búsqueda y ubicación de ese integrante de familia faltante en el hogar, son pocos los análisis e investigaciones que muestren y enseñen la gran problemática existente para el cumplimiento de estas funciones por parte del Estado. En su artículo 25 de la Ley 1448 de 2011 se encuentra definido el Derecho a la reparación integral de las víctimas, que comprende desde medidas de restitución, indemnización, rehabilitación, satisfacción y garantías de no repetición; en sus contextos individuales, colectivos, materiales, morales y simbólicos siendo a favor de las victimas dependiendo de la vulneración de sus derechos y las características del hecho victimizante en nuestro caso la desaparición forzada. En los dos parágrafos del citado artículo se encuentran consagradas las medidas de asistencia adicionales, los cuales no sustituyen o reemplazan a las medidas de reparació[email protected]@[email protected]@[email protected]

Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et)

Q2Q1Background: It has been proposed that polyphenols can be used in the development of new therapies against COVID-19, given their ability to interfere with the adsorption and entrance processes of the virus, thus disrupting viral replication. Seeds from Caesalpinia spinosa, have been traditionally used for the treatment of inflammatory pathologies and respiratory diseases. Our team has obtained an extract called P2Et, rich in polyphenols derived from gallic acid with significant antioxidant activity, and the ability to induce complete autophagy in tumor cells and reduce the systemic inflammatory response in animal models. Methods: In this work, a phase II multicenter randomized double-blind clinical trial on COVID-19 patients was designed to evaluate the impact of the P2Et treatment on the clinical outcome and the immunological parameters related to the evolution of the disease. The Trial was registered with the number No. NCT04410510∗. A complementary study in an animal model of lung fibrosis was carried out to evaluate in situ lung changes after P2Et in vivo administration. The ability of P2Et to inhibit the viral load of murine and human coronaviruses in cellular models was also evaluated. Results: Patients treated with P2Et were discharged on average after 7.4 days of admission vs. 9.6 days in the placebo group. Although a decrease in proinflammatory cytokines such as G-CSF, IL-15, IL-12, IL-6, IP10, MCP-1, MCP-2 and IL-18 was observed in both groups, P2Et decreased to a greater extent G-CSF, IL-6 and IL-18 among others, which are related to lower recovery of patients in the long term. The frequency of T lymphocytes (LT) CD3+, LT double negative (CD3+CD4-CD8-), NK cells increased in the P2Et group where the population of eosinophils was also significantly reduced. In the murine bleomycin model, P2Et also reduced lung inflammation and fibrosis. P2Et was able to reduce the viral replication of murine and human coronaviruses in vitro, showing its dual antiviral and anti-inflammatory role, key in disease control. Conclusions: Taken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19.https://orcid.org/0000-0001-5608-3181https://orcid.org/0000-0001-5133-2206https://orcid.org/0000-0001-8491-2952https://orcid.org/0000-0002-4622-0258https://orcid.org/0000-0002-3606-2102https://orcid.org/0000-0002-4664-0682Revista Internacional - IndexadaA1N

III Foro de humanismo digital : la revolución de los humanos

ilustraciones, imágenes, gráficos ; 28 cmLa ponencia estuvo dirigida a reflexionar acerca de las transformaciones en las prácticas educativas a partir de las contingencias causadas por el confinamiento asociado a las medidas de bioseguridad y autocuidado que se debieron tomar de manera global y local por la pandemia del COVID-19. Se describió cómo las nuevas di námicas implicaron un viraje en la manera como las comunidades académicas y las personas debieron ajustar su relación con las tecnologías y aplicaciones digitales, en especial en el ámbito del ejercicio de la enseñanza – aprendizaje, y cómo dichas transformaciones se convierten en herramientas que pueden mejorar los procesos educativos, laborales y de interacción, y dejan un legado que incide de manera significativa y propositiva en distintos ámbitos de la cotidianidad de docentes, estudiantes y responsables de los procesos educativos