RESUMO
Gastric cancer (GC)-diabetes co-morbidity is nowadays growing into a rising concern. However, no separate treatment procedures have been outlined for such patients. Phytochemicals and their derivatives can therefore be used as therapeutics as they have greater effectiveness, reduced toxicity, and a reduced likelihood of developing multi-drug resistance in cancer treatments. The present study intended to assess the therapeutic efficacy of Shatavarin-IV - a major steroidal saponin from the roots of Asparagus racemosus, in human gastric adenocarcinoma cell line under hyperglycemic conditions and explore its mechanism of action in controlling GC progression. For the present study, AGS cells were incubated in high glucose-containing media and the effects of Shatavarin-IV therein have been evaluated. Cell proliferation, confocal microscopic imaging, flow-cytometric analysis for cell cycle and apoptosis, immunoblotting, zymography, reverse zymography, wound-healing, colony formation, and invasion assays were performed. Shatavarin-IV has a prominent effect on AGS cell proliferation; with IC50 of 2.463 µ M under hyperglycemic conditions. Shatavarin-IV induces cell cycle arrest at the G0/G1 phase, thereby preventing hyperglycemia-induced excessive cell proliferation that later on leads to apoptotic cell death at 36 h of incubation. Shatavarin-IV further inhibits the migratory and invasive potential of AGS cells by altering the expression patterns of different EMT markers. It also inhibits MMP-9 while promoting TIMP-1 activity and expression; thereby regulating ECM turnover. This is the first report demonstrating the therapeutic efficacy of Shatavarin-IV against AGS cells grown in hyperglycemic conditions, implicating new insights into the treatment paradigm of patients with GC-diabetes co-morbidity.
Assuntos
Asparagus , Proliferação de Células , Transição Epitelial-Mesenquimal , Hiperglicemia , Saponinas , Humanos , Saponinas/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Asparagus/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Linhagem Celular Tumoral , Ciclo Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Movimento Celular/efeitos dos fármacosRESUMO
The shoots of Asparagus L. are consumed worldwide, although most species belonging to this genus have a restricted range, and several taxa remain unstudied. In this work, a total of four taxa from different locations were scrutinized and compared with cultivated A. officinalis. All shoots were screened for saponins via LC-MS, and in vitro antiproliferative activities against the HT-29 colorectal cancer cell line were assessed via the MTT assay. The total saponins (TS) contained in the crude extracts ranged from 710.0 (A. officinalis) to 1258.6 mg/100 g dw (A. acutifolius). The richness of the compounds detected in this work stands out; a total of 47 saponins have been detected and quantified in the edible parts (shoots) of five taxa of Asparagus. The structure of all the saponins found present skeletons of the furostane and spirostane type. In turn, the structures with a furostane skeleton are divided into unsaturated and dioxygenated types, both in the 20-22 position. The sum of dioscin and derivatives varied largely among the studied taxa, reaching the following percentages of TS: 27.11 (A. officinalis), 18.96 (A. aphyllus), 5.37 (A. acutifolius), and 0.59 (A. albus); while in A. horridus, this compound remains undetected. Aspachiosde A, D, and M varied largely among samples, while a total of seven aspaspirostanosides were characterized in the analyzed species. The hierarchical cluster analysis of the saponin profiles clearly separated the various taxa and demonstrated that the taxonomic position is more important than the place from which the samples were acquired. Thus, saponin profiles have chemotaxonomic significance in Asparagus taxa. The MTT assay showed dose- and time-dependent inhibitory effects of all saponins extracts on HT-29 cancer cells, and the strongest cell growth inhibition was exercised by A. albus and A. acutifolius (GI50 of 125 and 175 µg/mL). This work constitutes a whole approach to evaluating the saponins from the shoots of different Asparagus taxa and provides arguments for using them as functional foods.
Assuntos
Asparagus , Extratos Vegetais , Brotos de Planta , Saponinas , Saponinas/farmacologia , Saponinas/química , Humanos , Asparagus/química , Brotos de Planta/química , Células HT29 , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proliferação de Células/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/químicaRESUMO
Asparagus officinalis L. is a horticultural crop that contains a variety of bioactive compounds with anti-inflammatory effects. Aqueous extracts of A. officinalis can noticeably improve the learning and memory function of model mice. Herein, a pectin-arabinoglucuronogalactan complex (AOPB-1-1) with a relative molecular weight of 90.8 kDa was isolated from A. officinalis. The repeating structural unit of AOPB-1-1 was identified through monosaccharide composition, methylation analysis, uronic acid reduction, partial acid hydrolysis, and nuclear magnetic resonance spectroscopy. AOPB-1-1 contains the rhamnogalacturonan-I (RG-I) domain of pectin polysaccharides (PPs) and arabinoglucuronogalactan (AGG) regions. The backbone of the AGG region is composed of â3,6)-ß-D-Galp-(1â and â4)-ß-D-Glcp-(1â residues substituted at the 4-position to the â4)-α-D-GalAp-(1â residues of the RG-I main chain. The anti-neuroinflammatory activity of AOPB-1-1 suggests that it can significantly reduce the content of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2 (COX2), nitric oxide synthase (iNOS), TNF-α, IL-6, and interleukin-1ß (IL-1ß) in LPS-stimulated BV2 cells. Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.
Assuntos
Anti-Inflamatórios , Asparagus , Pectinas , Pectinas/farmacologia , Pectinas/química , Pectinas/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Asparagus/química , Animais , Camundongos , Galactanos/farmacologia , Galactanos/química , Galactanos/isolamento & purificação , Citocinas/metabolismo , Óxido Nítrico/metabolismo , Peso MolecularRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Despite various treatment modalities, the progression and metastasis of breast cancer (BC) are grave concerns due to the alarming disease-free survival rate (DFS) and overall survival rate (OS) of affected patients. Over the years, many antibiotics, synthetic compounds, medicinal plant isolates and polyherbal combinations have been used as adjuvants in therapy for the management of primary and secondary tumors. Paclitaxel (PTX)-based chemotherapy for breast cancer causes multiple adverse side effects in patients. Withania somnifera (L.) Dunal (WS) and Asparagus racemosus Willd. (AR) as Ayurveda-inspired plant-based adjuvants were investigated for their anticancer effects on MDA-MB-231 and 4T1 cells in mouse model systems. AIM OF THE STUDY: This study focused on evaluating the adjuvant properties of WS and AR plant extracts with PTX and their effectiveness over PTX alone in terms of tumor inhibition. MATERIALS AND METHODS: The effects of WS and AR on DNA double-strand breaks (DSBs), senescence induction and mitochondrial functions were evaluated in BC cells in vitro. The potential for cancer stem cell (CSC) inhibition was evaluated via mammosphere formation assays and CD44/CD24 immunostaining. In vivo tumor growth studies were conducted in athymic BALB/c mice for MDA-MB-231 cells and in BALB/c mice for 4T1 cells. RESULTS: Induction of senescence was evident due to DSBs induced by the WS and AR extracts. Mammosphere formation and CD44/CD24 CSC markers were reduced after treatment with WS, AR or the combination of both in MCF-7 cells. WS or AR inhibited epithelial-to-mesenchymal transition (EMT). In vivo studies demonstrated that tumor growth inhibition was more pronounced in the treated group than in the PTX alone group and the untreated control group. CONCLUSION: Our study showed that the use of WS or AR plant hydroalcoholic extracts in combination with paclitaxel (PTX) has better effects on sensitivity and efficacy than PTX alone, as demonstrated in in vitro BC cells and mouse models with BC cell grafts. Hence, scheduling adjuvant therapy with WS or AR alone or combined with PTX can be advantageous for the management of triple-negative BC (TNBC). Further studies are warranted in human clinical conditions to ascertain the efficacy of these treatments.
Assuntos
Asparagus , Neoplasias da Mama , Camundongos Endogâmicos BALB C , Paclitaxel , Extratos Vegetais , Withania , Animais , Asparagus/química , Humanos , Withania/química , Feminino , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Linhagem Celular Tumoral , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Camundongos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos Fitogênicos/isolamento & purificação , Antígeno CD24/metabolismo , Receptores de Hialuronatos/metabolismo , Adjuvantes Farmacêuticos/farmacologia , Senescência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacosRESUMO
Background: Asparagus (Asparagus officinalis L.) green is a vegetable with a great demand worldwide, and likewise, it is highly perishable, due to its high respiration rate that accelerates its senescence. Disinfection of vegetables after their harvest is an obligatory practice that can reduce losses by decomposition due to the attack of microorganisms. Therefore, it is vital to preserving its microbiological and sensory characteristics to reach the final consumer. Objective: to evaluate the effect of gaseous ozone (0 to 10 ppm) and storage time (0 to 30 days) on phenol content, overall appearance, count of molds, psychrophilic bacteria, and viable mesophilic aerobes. Methods: the response surface methodology was used, applying a rotatable central composite design. Results: the results indicated that there was a significant influence (p <0.05) of the independent variables on the characteristics studied, as well as an adequate lack of fit of the quadratic regression model (p> 0.05). By means of the contour superposition technique, it was determined that the optimal conditions for the highest retention of phenol content (16.99 mg/g) and overall appearance (7.61 points) and lower counts of viable aerobic mesophilic bacteria (5.3 x 103 CFU/g) they corresponded to 10 ppm of gaseous ozone up to 25.91 days of storage, with adequate quality characteristics in the spears. Conclusion: the region of interest was determined for optimal retention of phenol content and overall appearance, and a lower count of viable aerobic mesophilic bacteria in green asparagus during postharvest, suggesting to use the initial application of ozone gas at 10 ppm allowing 25.9 days storage at 1 °C. The results indicate that this technology is a good alternative in the conservation of fresh vegetables
Antecedentes: El espárrago (Asparagus officinalis L.) verde; es una hortaliza con una gran demanda a nivel mundial, y, asimismo, es altamente perecible, por su elevada velocidad de respiración que, acelera su proceso de senescencia. La desinfección de los vegetales después de su cosecha es una práctica obligada que puede disminuir las pérdidas por descomposición debido al ataque de microrganismos. Por lo tanto, es muy importante conservar sus características microbiológicas y sensoriales para llegar al consumidor final. Objetivo: evaluar el efecto del ozono gaseoso (0 a 10 ppm) y tiempo de almacenamiento (0 a 30 días) sobre el contenido de fenoles, apariencia general, recuento de mohos, bacterias psicrófilas y aerobias mesófilas viables. Métodos: se utilizó la metodología de superficie de respuesta, aplicando un diseño compuesto central rotable. Resultados: los resultados indicaron que existió influencia significativa (p<0.05) de las variables independientes sobre las características estudiadas, así como, una adecuada bondad de ajuste del modelo de regresión cuadrático (p>0.05). Mediante la técnica de superposición de contornos se determinó que las condiciones óptimas para la mayor retención de contenido de fenoles (16.99 mg/g) y apariencia general (7.61 puntos) y menor recuentos de bacterias aerobias mesófilas viables (5.3 x 103 UFC/g) correspondieron a 10 ppm de ozono gaseoso hasta los 25.91 días de almacenamiento, con adecuadas características de calidad en los turiones. Conclusión: se determinó la región de interés para una óptima retención de contenido de fenoles y apariencia general, así como, menor recuento de bacterias aerobias mesófilas viables en el espárrago verde durante la postcosecha, sugiriendo utilizar la aplicación inicial de ozono gaseoso a 10 ppm permitiendo 25.9 días de almacenamiento a 1 °C. Los resultados indican que esta tecnología es una buena alternativa en la conservación de hortalizas frescas
Assuntos
Humanos , Asparagus , Ozônio , FenóisRESUMO
Introdução: O aspargo é tido popularmente como suplemento alimentar eficaz no tratamento do câncer. Objetivo: Avaliar a eficiência da suplementação de aspargo no tratamento ou na prevenção de câncer. Métodos: Por meio de uma revisão sistematizada da literatura (Lilacs, Medline, Colaboração Cochrane, PubMed), procurou-se evidência, em artigos científicos, da ação do aspargo no tratamento do câncer. Não houve restrição a idade, idioma ou tipo de câncer, assim como o tipo de publicação não ficou restrito aos de melhores qualidades metodológicas. Resultados: Não foram encontrados estudos. Conclusão: Não há evidência, na literatura mundial, da eficácia da suplementação de aspargo no tratamento ou prevenção do câncer.
Assuntos
Práticas Alopáticas , Asparagus , Medicina Baseada em Evidências , Neoplasias , Medicamento FitoterápicoRESUMO
OBJECTIVE: Asparagusracemosus Willd has been used as diuretic in Ayurveda but has not been validated by a suitable experimental model. Hence the present study was undertaken. MATERIALS AND METHODS: The study was carried out with an aqueous extract of the roots of Asparagus racemosus utilizing three doses viz 800 mg/kg, 1600 mg/kg and 3200 mg/kg for its diuretic activity in comparison with standard drug (furosemide) and control (normal saline) rats after doing acute toxicity study. RESULTS: Acute toxicity study showed no fatality even with the highest dose and the diuretic study revealed significant diuretic activity (p < 0.05) in the dose of 3200 mg/kg. CONCLUSION: Asparagus racemosus showed diuretic activity at a 3200 mg/kg dose without acute toxicity.
OBJETIVO: El espárrago racemoso Willd ha sido usado como diurético en ayurveda pero no ha sido validado mediante un modelo experimental conveniente. De ahí la razón para emprender el presente estudio. MATERIALES Y MÉTODOS: El estudio fue realizado con extracto acuoso de raíces de espárrago racemoso, utilizando tres dosis, a saber, 800 mg/kg, 1600 mg/kg y 3200 mg/kg para analizar su actividad diurética, comparándolo con el medicamento estándar (furosemida), y ratas de control (solución salina normal) después de hacer un estudio de toxicidad aguda. RESULTADOS: El estudio de toxicidad aguda no mostró fatalidad, incluso con la dosis más alta, y el estudio del diurético reveló una actividad diurética significativa (p < 0.05) con la dosis de 3200 mg/kg. CONCLUSIÓN: El espárrago racemoso mostró actividad diurética en una dosis de 3200 mg/kg sin toxicidad aguda.