RESUMO
The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC50 value lower than that of the reference drug - temozolomide - in the most responsive cell line - SK-MEL-147 - and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC50 = 13.09 µg/mL and selectivity index = 3.82; temozolomide, IC50 = 121.50 µg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations.
Assuntos
Antineoplásicos Fitogênicos , Croton , Lignanas , Melanoma , Metabolômica , Folhas de Planta , Humanos , Linhagem Celular Tumoral , Melanoma/tratamento farmacológico , Croton/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Lignanas/farmacologia , Lignanas/isolamento & purificação , Folhas de Planta/química , Estrutura Molecular , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proliferação de Células/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Furanos/farmacologia , Furanos/isolamento & purificaçãoRESUMO
Melanoma is a cancer type with high lethality, metastatic capacity, and limited therapeutic options. Different essential oils have been reported with antitumoral potential. Thus, the essential oil (EO) of the leaves of C. floribundus was obtained by hydrodistillation and analyzed by GC-MS. The majority of substances annotated were ß-selinene, E-Caryophyllene, and Premnaspirodiene. The cytotoxic activity of EO was evaluated on three melanoma cell lines SKMEL-147, WM-1366, and CHL-1, which are representative of metastatic melanoma with different mutation profiles. The IC50 values found for EO were lower than temozolomide (reference drug) in all melanoma cell lines. In addition, the selectivity of EO was upward when compared to the reference drug. Interestingly, the WM-1366â cell line was the most responsive, and these findings are very promising considering that it has shown high resistance to the plethora of compounds. Thus, the C. floribundus EO is a promising source to drive further studies for the development of new treatments for metastatic melanoma, which is urgently relevant given the resistance of this pathology to current treatments.
Assuntos
Antineoplásicos Fitogênicos , Proliferação de Células , Croton , Ensaios de Seleção de Medicamentos Antitumorais , Melanoma , Óleos Voláteis , Folhas de Planta , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Folhas de Planta/química , Melanoma/tratamento farmacológico , Melanoma/patologia , Croton/química , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Relação Dose-Resposta a Droga , Sobrevivência Celular/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Species Cissus gongylodes has been used in the traditional medicine in South America and India for the treatment of urolithiasis, biliary and inflammatory problems without any scientific evidence. AIM OF THE STUDY: This work was developed to investigate for the first time the anti-inflammatory and anti-urolithiatic activities of leaf decoction of C. gongylodes. MATERIALS AND METHODS: Decoction was subjected to anti-inflammatory evaluation by the in vivo assay of ear oedema and quantification of the main mediators of inflammation PGE2 and LTB4, and the cytokine TNF-α. The decoction's anti-urolithiatic activity was determined by different in vitro assays to evaluate the inhibition and dissolution of the most prevalent types of kidney stones: calcium oxalate (CaOx) and struvite. Diffusion in gel technique and fresh urine of a patient with renal stone were used to investigate the inhibition and dissolution of CaOx, respectively, and the single diffusion gel growth technique was used to evaluate the inhibition and dissolution of struvite crystals. The decoction was chemically characterized by UHPLC-ESI-HRMS analysis. RESULTS: Decoction showed in vivo anti-inflammatory activity by potent decreasing the level of both the main mediators of inflammation and dose-dependent in vitro anti-urolithiatic action by inhibition and dissolution of both type of crystals, CaOx and struvite. CONCLUSIONS: Results obtained corroborate the reports of the traditional use of the decoction of Cissus gongylodes. Besides, it showed multi-target mechanisms actions, inhibition of the main inflammatory pathways, and inhibition/dissolution of the most prevalent types of crystals on urolithiasis. These actions make the decoction a promissory source to the development of new and more efficient drugs.
Assuntos
Anti-Inflamatórios/uso terapêutico , Cissus , Edema/tratamento farmacológico , Cálculos Renais/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Oxalato de Cálcio/química , Óleo de Cróton , Cristalização , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Humanos , Cálculos Renais/química , Leucotrieno B4/metabolismo , Masculino , Camundongos , Extratos Vegetais/química , Folhas de Planta , Estruvita/química , Fator de Necrose Tumoral alfa/metabolismoRESUMO
There is increasing recognition that ecosystems and their services need to be managed at landscape scale and greater. The development of landscape-scale conservation strategies need to incorporate information from multiple sources. In this study, we combine various research tools to link landscape patterns with production units and systems in the Usumacinta River Basin, and inform the discussion of key questions around decision-making related to conservation action and policy in Southern Mexico. A typology based on policy-relevant farmer characteristics (land tenure, farm size, source of income, farming system) differentiated between farmers (traditional vs. cattle ranching) with different motivations that determine how management affects landscape configuration. Five main types of traditional farming systems were identified that combine different forms of land use and vary in their degree of land intensification. Major fragmentation and decrease in connectivity coincided spatially with floodplains dominated by large-scale commercial farms that specialize in livestock production. Traditional practices within large units with low-sloped high quality land were also seen to be intensive; however the presence of trees was notable throughout these units. Policies that promote livestock farming are among the principle causes motivating deforestation. Land intensification by traditional farmers decreased as the landscape became increasingly rugged. Traditional farmers are the focus of initiatives developed by the Biological Corridor project which seeks to increase forest cover and landscape connectivity. These initiatives have shown high levels of rural participation (10,010 farmers benefited from 27,778 projects involving 95,374â¯ha of land) and acceptance (producers carried out more than one project and several types of projects during the first eight years of work). Strong action is still required to take on the segment of large-scale ranchers. Changes in the structure of land tenure over the past decade are highlighted that could have a profound impact on conservation policies and programs.
Assuntos
Agricultura , Rios , Agricultura/métodos , Animais , Bovinos , Conservação dos Recursos Naturais , Ecossistema , Fazendeiros , Fazendas , Renda , México , ÁrvoresRESUMO
Modern high-resolution ultrasound images enable earlier assessment of measures of fetal development, including identification of the bowel. The aim of this study was to describe the ultrasonographic development of fetal bowel and correlate this with gestational age; define whether ultrasonographic visualization of fetal intestinal peristalsis in utero is associated with fetal maturation and determine whether there is a difference in fetal intestinal peristalsis detection time between fetuses delivered by normal delivery and cesarean. A cohort study was conducted in pregnant bitches presented to a veterinary hospital, to assess fetal bowel development. Statistical analysis was used to establish the correlation of the stage of fetal bowel development, as recorded by ultrasound, with outcomes of normal delivery and cesarean section. The study was broken down into three stages: the first stage was a descriptive analysis of fetal bowel development by ultrasound; the second stage compared time (in days) of bowel development between groups (normal delivery vs. cesarean); and the third stage was correlated survival probability for fetuses born on any day after detection of intestinal peristalsis with fetal maturity. All statistical analyses were significant. It is possible to monitor pregnancy progression using ultrasonographic evaluation of bowel development and this can reliably identify the end of fetal organogenesis. However, ultrasonographic detection of bowel segments with visualization of wall layers and associated peristalsis should not be used as the sole indicator for cesarean section planning because it is not possible to determine ultrasonographically whether the bowel is functional (mature).