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Cancer is an important disease that causing to deaths in the world. Cervical cancer is one of the most common among women and must be treated quickly to prevent cell proliferation. Natural products have been used for cancer treatment due to their antiproliferative and apoptosis induction properties. In the present study, we aimed to determine the antiproliferative and apoptosis induction activities of methanol extract of Inula graveolens (IGME) in the human cerival cancer cell line (HeLa). Antiproliferative activity of IGME was evaluated by using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) method. Apoptosis induction activity was determined by AnnexinV/propodium iodide staining with FACS. ROS induction was determined by DCFH-DA (2',7'-Dichlorofluorescin diacetate) staining. Interleukin 6 and 8 levels (IL-6 and IL-8) were determined by the Elisa method. IGME exhibited antiproliferative effect and induced apoptosis in the HeLa cells. IL-6, IL-8 and intracellular ROS levels were decreased after treatment of IGME. Consequently, IGME was found to have antiproliferative and apoptosis induction activities as an indicator of the anticancer activity.

El cáncer es una enfermedad importante que causa muertes en el mundo. El cáncer de cuello uterino es uno de los más comunes entre las mujeres y debe tratarse rápidamente para evitarla proliferación celular. Los productos naturales se han utilizado para el tratamiento del cáncer debido a sus propiedades anti proliferativas y de inducción de la apoptosis. En el presente estudio, nuestro objetivo fue determinar las actividades de inducción de apoptosis y antiproliferativas del extracto de metanol de Inula graveolens (IGME) en la línea celular de cáncer de cuello uterino humano (HeLa). La actividad antiproliferativa de IGME se evaluó utilizando el método MTT (bromuro de 3-[4,5-dimetiltiazol-2-il]-2,5-difenil-tetrazolio). La actividad de inducción de apoptosis se determinó mediante tinción con anexina V/yoduro de propodio con FACS. La inducción de ROS se determinó mediante tinción con DCFH-DA (diacetato de 2',7'-diclorofluoresceina). Los niveles de interleucina 6 y 8 (IL-6 e IL-8) se determinaron por el método Elisa. IGME exhibió un efecto antiproliferativo e indujo apoptosis en las células HeLa. Los niveles de IL-6, IL-8 y ROS intracelulares disminuyeron después del tratamiento con IGME. En consecuencia, se encontró que IGME tenía actividades antiproliferativas y de inducción de apoptosis como indicador de la actividad anticancerígena.

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OBJECTIVE: Crude oil extracts, components of extracts, and ethanolic extracts of Inula graveolens possess various pharmacological activities on various cancer cells including antioxidative and antiproliferative effects. Aqueous extract of this species has not been investigated on the liquid malignancies and solid tumors with a high incidence of treatment refractoriness and poor survival outcomes such as glioblastoma and leukemia. Hence, the present study aimed to evaluate the cytotoxic efficiency of I. graveolens aqueous extracts on human glioblastoma multiforme and chronic myelogenous leukemia cell lines in comparison to non-cancerous primary rat cerebral cortex and human peripheral blood mononuclear cells. METHODS: The cells were treated with the extracts of I. graveolens (125-1000 µg/mL) for 48 h, the cellular viability was identified using 3'-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and lactate dehydrogenase release was measured to determine the cytotoxic potential. Total oxidant status and apurinic/apyrimidinic endodeoxyribonuclease 1 assays were used to determine the oxidative status of cells and DNA damage, respectively. RESULTS: I. graveolens showed selective cytotoxicity toward human glioblastoma multiforme and chronic myelogenous leukemia cell lines and exhibited a higher antiproliferative effect against cancer cells in comparison to non-cancerous cells. Moreover, it significantly reduced the apurinic/apyrimidinic endodeoxyribonuclease 1 levels on both cancer cell lines as compared with their control cells without changing the levels of an oxidative stress marker. CONCLUSION: The extracts of I. graveolens have anti-cancer potential on human glioblastoma multiforme and chronic myelogenous leukemia cell lines without causing oxidative stress.

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Reactive oxygen species are implicated in multiple pathological conditions including erectile dysfunction. This study evaluated the in vitro and in vivo antioxidant potential of the methanolic extracts of Inula glomerata and Salacia kraussii. The plant materials were pulverized and extracted with methanol. The phytochemical analysis, ability of the crude extracts to scavenge free radicals (ABTS, DPPH, NO.) in vitroas well as the total phenolic and flavonoid contents was investigated. In vivo, antioxidant potentials of the crude extracts (50/250 mg/kg body weight) were determined in an erectile dysfunction rat model. The phytochemical analysis revealed that both plants contain flavonoids, tannins, terpenoids, and alkaloids. The crude extracts at varying degree of efficiency, scavenged ABTS and DPPH radicals. The crude extracts at low concentrations (50 mg/kg b.w) significantly (p<0.05) diminished the level of malondialdehyde, augmented catalase activities and elevated glutathione levels. However, SOD activities were significantly boosted in a dose-dependent manner by the crude extracts. Therefore, I. glomerataand S. kraussiipossess antioxidant properties, hence, can serve as a therapeutic modality in the treatment of oxidative stress-induced erectile dysfunction.

Las especies reactivas de oxígeno están implicadas en múltiples condiciones patológicas, incluyendo la disfunción eréctil. Este estudio evaluó el potencial antioxidante in vitro e in vivo de extractos metanólicos de Inula glomeratay Salacia kraussii. Los materiales vegetales fueron pulverizados y extraídos con metanol. A estos extractos crudos se les llevó a cabo el análisis fitoquímico junto con el contenido total de fenólicos y flavonoides, así como se les investigó la capacidad in vitro para atrapar radicales (ABTS, DPPH, NO.). Los potenciales antioxidantes in vivo de los extractos crudos (50/250 mg/kg de peso corporal) se determinaron en un modelo en ratas con disfunción eréctil. El análisis fitoquímico reveló que ambas plantas contuvieron flavonoides, taninos, terpenoides y alcaloides. Los extractos crudos con un grado variable de eficiencia, atraparon a los radicales ABTS y DPPH. Los extractos crudos a bajas concentraciones (50 mg/kg p.c) significativamente (p<0.05) disminuyeron el nivel de malondialdehído, aumentaron las actividades de catalasa y elevaron los niveles de glutatión. Sin embargo, las actividades de SOD por los extractos crudos fueron significativamente dosis-dependientes. Así, los extractos de I. glomeratay S. kraussii mostraron propiedades antioxidantes, y por lo tanto, podrían servir como una alternativa terapéutica en el tratamiento de disfunción eréctil inducida por estrés oxidativo.

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Inula aucheriana DC is a member of the family Asteraceae which is known to produce cytotoxic secondary metabolites noted as sesquiterpene lactones. In the present study, sesquiterpene lactones inuchinenolide B, 6-deoxychamissonolide (stevin) and 14-acetoxy-1ß,5α,7αH-4ß-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were isolated from I. aucheriana. Inuchinenolide B and 14-acetoxy-1ß,5α,7αH-4ß-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were further evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay to demonstrate cytotoxic activity with IC50 values of (56.6, 19.0), (39.0, 11.8), and (55.7, 15.3) µg/mL against HepG-2, MCF-7 and A-549 cells, respectively. The cytotoxic activity of the two evaluated sesquiterpene lactones partly explains the cytotoxic activity that was previously observed for the extracts of Inula aucheriana. The isolated compounds could be further investigated in cancer research studies.

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