RESUMO
This study aimed to assess dark sweet cherry (DSC) total polyphenols (WE) and anthocyanins (ACN) against metastatic breast cancer (BC). The WE and ACN anticancer activity and underlying mechanisms were assessed in vitro using 4T1 BC cells. A pilot study using a BALB/C mouse syngeneic model bearing 4T1 tumors assessed the anti-metastatic potential of ACN in vivo. ACN inhibited cell viability with higher potency than WE and reduced reactive oxygen species (ROS) (IC50 = 58.6 µg cyanidin 3-glucoside equivalent (C3G)/mL or 122 µM). ACN induced p38 stress-related intrinsic apoptosis, leading to caspase-3 cleavage and total PARP decrease. ACN suppressed ERK1/2 and Akt/mTOR signaling pathways, which are abnormally activated in BC and promote motility and invasion. This was consistent with suppression of VCAM-1 mRNA, Scr phosphorylation and 88.6% reduction of cells migrating to wounded area. The pilot in vivo results supported the ACN-mediated suppression of angiogenesis in tumors and lungs. ACN also lowered Cenpf mRNA in lungs, associated with lung metastasis lesions and poor survival. Results demonstrated the dual Akt-ERK inhibitory role of ACN and suppression of their downstream pro-invasive targets. These results encourage a larger scale in vivo study to confirm that ACN may help to fight BC invasion and metastasis.
Assuntos
Prunus avium , Neoplasias de Mama Triplo Negativas , Animais , Humanos , Camundongos , Antocianinas/farmacologia , Antocianinas/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Projetos Piloto , Proteínas Proto-Oncogênicas c-akt/metabolismo , Prunus avium/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
The aim of this review was to compile evidence and understand chia seed effects on unbalanced diet animal studies and the molecular mechanisms on metabolic biomarker modulation. A systematic review was conducted in electronic databases, following PRISMA recommendations. Risk of bias and quality was assessed using SYRCLE toll and ARRIVE guidelines. Seventeen articles were included. Throughout the studies, chia's main effects are associated with AMPK modulation: improvement of glucose and insulin tolerance, lipogenesis, antioxidant activity, and inflammation. Details about randomization and allocation concealment were insufficient, as well as information about blind protocols. Sample size, chia dose, and number of animals evaluated for each parameter were found to be lacking information among the studies. Based on experimental study data, chia has bioactive potential, and its daily consumption may reduce the risk of chronic disease development, mainly due to the antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic effects of the seed. PRACTICAL APPLICATION: The consumption of chia seeds may improve lipid profile, insulin and glucose tolerance, and reduce risk of cardiovascular disease. Whole seed or its oil presents positive effect, but the effects of chia oil can act faster than the seed.
Assuntos
Doenças Cardiovasculares/metabolismo , Salvia/metabolismo , Animais , Glucose/metabolismo , Humanos , Insulina/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Camundongos , Ratos , Salvia/química , Sementes/química , Sementes/metabolismoRESUMO
Malaria remains a major detrimental parasitic disease in the developing world, with more than 200 million cases annually. Widespread drug-resistant parasite strains push for the development of novel antimalarial drugs. Plant-derived natural products are key sources of antimalarial molecules. Euterpe oleracea Martius ("açaí") originates from Brazil and has anti-inflammatory and antineoplasic properties. Here, we evaluated the antimalarial efficacy of three phenolic fractions of açaí; total phenolics (1), nonanthocyanin phenolics (2), and total anthocyanins (3). In vitro, fraction 2 moderately inhibited parasite growth in chloroquine-sensitive (HB3) and multiresistant (Dd2) Plasmodium falciparum strains, while none of the fractions was toxic to noncancer cells. Despite the limited activity in vitro, the oral treatment with 20 mg/kg of fraction 1 reduced parasitemia by 89.4% in Plasmodium chabaudi-infected mice and prolonged survival. Contrasting in vitro and in vivo activities of 1 suggest key antiplasmodial roles for polyphenol metabolites rather than the fraction itself. Finally, we performed haploinsufficiency chemical genomic profiling (HIP) utilizing heterozygous Saccharomyces cerevisiae deletion mutants to identify molecular mechanisms of açaí fractions. HIP results indicate proteostasis as the main cellular pathway affected by fraction 2. These results open avenues to develop açaí polyphenols as potential new antimalarial candidates.
RESUMO
Cocoplum (Chrysobalanus icaco L.) (CP) is an anthocyanin-rich fruit found in tropical areas around the globe. CP polyphenols are associated with beneficial effects on health, including reduction of inflammation and oxidative stress. Due to its functional properties, the consumption of this fruit may be beneficial in the promotion of human health and reduce the risk for chronic diseases. The objective of this study was to assess the anti-inflammatory and anti-proliferative activities of anthocyanins extracted from CP (1.0 to 20.0 µg ml-1 gallic acid equivalents [GAE]) in CCD-18Co non-malignant colonic fibroblasts and HT-29 colorectal adenocarcinoma cells. Tumor necrosis factor alpha (TNF-α, 10 ng mL-1) was used to induce inflammation in CCD-18Co cells. CP anthocyanins were identified and quantified using HPLC-ESI-MSn. The chemical analysis of CP extract identified delphinidin, cyanidin, petunidin and peonidin derivatives as major components. Cell proliferation was suppressed in HT-29 cells at 10.0 and 20.0 µg ml-1 GAE and this was accompanied by increased intracellular ROS production as well as decreased TNF-α, IL-1ß, IL-6, and NF-κB1 expressions at 20.0 µg ml-1 GAE. Within the same concentration range, there was no cytotoxic effect of CP anthocyanins in CCD-18Co cells and TNF-α-induced intracellular ROS-production was decreased by 17.3%. IL-1ß, IL-6 and TNF-α protein expressions were also reduced in TNF-α-treated CCD-18Co cells by CP anthocyanins at 20.0 µg ml-1 GAE. These results suggest that cocoplum anthocyanins possess cancer-cytotoxic and anti-inflammatory activities in both inflamed colon and colon cancer cells.
Assuntos
Antocianinas/farmacologia , Anti-Inflamatórios/farmacologia , Chrysobalanaceae/química , Extratos Vegetais/farmacologia , Antocianinas/química , Anti-Inflamatórios/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colo/citologia , Colo/efeitos dos fármacos , Colo/metabolismo , Neoplasias do Colo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Anthocyanins (ANC) are common polyphenolics in plants, but are poorly absorbed into the bloodstream upon consumption. Phospholipids (PL) and terpenes (TP) may serve as enhancing agents in absorption. This study evaluated their role in transepithelial transport within a Caco-2 cell monolayer-model system and impact on ANC stability. Açaí fruit ANC were isolated and found to transport, at a low rate (1.22%), in the absence of soy lecithin phospholipids and Valencia orange terpenes, yet their addition significantly increased the transport of both cyanidin-3-glucoside and cyanidin-3-rutinoside. The best transport results (5.21%) were observed when combinations of PL (5000 mg/l) and TP (50mg/l) were used. The presence of PL and TP had no influence on ANC degradation over a 40 day storage period. Results demonstrated the potential of PL and TP to increase intestinal transport of ANC, and present advancement towards the formulation of functional foods that support improved ANC absorption.
Assuntos
Antocianinas/química , Euterpe/química , Frutas/química , Fosfolipídeos/química , Terpenos/química , Antocianinas/farmacocinética , Transporte Biológico , Células CACO-2 , Humanos , Mucosa Intestinal/metabolismo , Fosfolipídeos/farmacocinética , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Terpenos/farmacocinéticaRESUMO
Phenolic extracts obtained from spices are known to have anti-carcinogenic activities but little is known about the effect of micropropagation on these beneficial effects. The main objective of this study was to evaluate the cytotoxic activity of flavonoid-enriched extracts (FEE) from the leaves of wild (WT), in vitro (IN), and ex vitro (EX) grown oregano plants in colon cancer cells HT-29 and the non-cancer cells CCD-18Co. Cell proliferation of HT-29 cells was reduced to 50 % by WT, IN, and EX at concentrations of 4.01, 1.32, and 4.84 mg of gallic acid equivalents (GAE)/L, respectively. In contrast, in CCD-18Co cells, higher concentrations were required for the same cytotoxic effect. At 6 mg GAE/L, WT and IN reduced the production of reactive oxygen species (ROS) of lipopolysaccharides (LPS)-stimulated control cells to 59.89 and 59.43 %, respectively, and EX to 73.89 %. The mRNA of Caspase-3 was increased 1.53-fold when cells were treated with 4 mg GAE/L of IN extract, and tumor necrosis factor receptor superfamily, member 6 (FAS), and BCL2-associated X protein (BAX) mRNA increased 2.55 and 1.53 fold, respectively. Results on protein expression corroborated the apoptotic effects with a significant decrease of B-cell lymphoma 2 (BCL2) expression for all treatments but more remarkable for EX that also showed the most intense signal of BAX. Overall, FEE extracts derived from micropropagation had increased pro-apoptotic effects, however extracts from the in vitro plants produced more efficacy at the transcriptional level while extracts from the ex vitro plant were superior at the traductional level.
Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Flavonoides/farmacologia , Lamiaceae/química , Lamiaceae/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Anticarcinógenos/química , Apoptose/efeitos dos fármacos , Apoptose/genética , Caspase 3/genética , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Flavonoides/análise , Células HT29/efeitos dos fármacos , Humanos , Lipopolissacarídeos/farmacologia , Fenóis/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Técnicas de Cultura de Tecidos , Proteína X Associada a bcl-2/genéticaRESUMO
Phytochemical analysis of the antioxidant ethanolic extract of Alternanthera tenella Colla led to the isolation of six flavonoids, acacetin 8-C-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranoside] (1), 2"-O-alpha-L-rhamnopyranosyl-vitexin (2), 2"-O-beta-D-glucopyranosyl-vitexin (3), vitexin (4), quercetin (5) and kaempferol (6). All the structures were established by ESI-MS and NMR spectroscopic methods. Antioxidant capacity of extract, fractions and isolated compounds was determined using the oxygen radical absorbance capacity (ORAC) assay and extract, fractions and flavonoids isolated showed antioxidant activity in vitro. Moreover, the total soluble phenolic contents of the extract and fractions were measured using the Folin-Ciocalteau reagent and the quantitative analysis of flavone C-glycosides major constituents was performed by HPLC.