Cinnamon Shows Antidiabetic Properties that Are Species-Specific : Effects on Enzyme Activity Inhibition and Starch Digestion

The study was funded by the Rural and Environment Science and Analytical Services Division of the Scottish government (RESAS). The authors are grateful to Phyllis Nicol for assisting with AGE measurements.Peer reviewedPublisher PD

Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer

BACKGROUND: There is a probable association between consumption of fruit and vegetables and reduced risk of cancer, particularly cancer of the digestive tract. This anti-cancer activity has been attributed in part to anti-oxidants present in these foods. Raspberries in particular are a rich source of the anti-oxidant compounds, such as polyphenols, anthocyanins and ellagitannins. METHODS: A "colon-available" raspberry extract (CARE) was prepared that contained phytochemicals surviving a digestion procedure that mimicked the physiochemical conditions of the upper gastrointestinal tract. The polyphenolic-rich extract was assessed for anti-cancer properties in a series of in vitro systems that model important stages of colon carcinogenesis, initiation, promotion and invasion. RESULTS: The phytochemical composition of CARE was monitored using liquid chromatography mass spectrometry. The colon-available raspberry extract was reduced in anthocyanins and ellagitannins compared to the original raspberry juice but enriched in other polyphenols and polyphenol breakdown products that were more stable to gastrointestinal digestion. Initiation – CARE caused significant protective effects against DNA damage induced by hydrogen peroxide in HT29 colon cancer cells measured using single cell microgelelectrophoresis. Promotion – CARE significantly decreased the population of HT29 cells in the G(1 )phase of the cell cycle, effectively reducing the number of cells entering the cell cycle. However, CARE had no effect on epithelial integrity (barrier function) assessed by recording the trans-epithelial resistance (TER) of CACO-2 cell monolayers. Invasion – CARE caused significant inhibition of HT115 colon cancer cell invasion using the matrigel invasion assay. CONCLUSION: The results indicate that raspberry phytochemicals likely to reach the colon are capable of inhibiting several important stages in colon carcinogenesis in vitro

Differential effects of polyphenols on proliferation and apoptosis in human myeloid and lymphoid leukemia cell lines.

Background: Mortality rates for leukemia are high despite considerable improvements in treatment. Since polyphenols exert pro-apoptotic effects in solid tumors, our study investigated the effects of polyphenols in haematological malignancies. The effect of eight polyphenols (quercetin, chrysin, apigenin, emodin, aloe-emodin, rhein, cis-stilbene and trans-stilbene) were studied on cell proliferation, cell cycle and apoptosis in four lymphoid and four myeloid leukemic cells lines, together with normal haematopoietic control cells. Methods: Cellular proliferation was measured by CellTiter-Glo® luminescent assay; and cell cycle arrest was assessed using flow cytometry of propidium iodide stained cells. Apoptosis was investigated by caspase-3 activity assay using flow cytometry and apoptotic morphology was confirmed by Hoescht 33342 staining. Results: Emodin, quercetin, and cis-stilbene were the most effective polyphenols at decreasing cell viability (IC50 values of 5-22 µM, 8-33 µM, and 25-85 µM respectively) and inducing apoptosis (AP50 values (the concentration which 50% of cells undergo apoptosis) of 2-27 µM, 19-50 µM, and 8-50 µM respectively). Generally, lymphoid cell lines were more sensitive to polyphenol treatment compared to myeloid cell lines, however the most resistant myeloid (KG-1a and K562) cell lines were still found to respond to emodin and quercetin treatment at low micromolar levels. Non-tumor cells were less sensitive to all polyphenols compared to the leukemia cells. Conclusions: These findings suggest that polyphenols have anti-tumor activity against leukemia cells with differential effects. Importantly, the differential sensitivity of emodin, quercetin, and cis-stilbene between leukemia and normal cells suggests that polyphenols are potential therapeutic agents for leukemia

Benzothiadiazole induces the accumulation of phenolics and improves resistance to powdery mildew in strawberries

Benzothiadiazole (BTH) enhanced the accumulation of soluble and cell-wall-bound phenolics in strawberry leaves and also improved the resistance to powdery mildew infection under greenhouse conditions. The most pronounced change was seen in the levels of ellagitannins, which increased up to 2- to 6-fold 4 days after the BTH application, but persisted only in the inoculated plants. The induction of phenolic metabolism by BTH was also reflected in the fruits, several compounds being increased in inoculated, BTH-treated plants. Basal salicylic acid (SA) content was high in strawberry leaves, but increased in a similar fashion to other phenolics after the treatments. Several phenolic compounds were identified in strawberries for the first time. For example, ellagic acid deoxyhexose, three agrimoniin-like ellagitannins, sanguiin H-10- and lambertianin C-like ellagitannins in the leaves, ellagic acid, p-coumaric acid, gallic acid, and kaempferol hexose in the cell-wall-bound fraction of the leaves, and kaempferol malonylglucoside in the fruits. The findings show that BTH can enhance the accumulation of phenolics in strawberry plants which may then be involved in the BTH-induced resistance to powdery mildew

Light manipulation as a route to enhancement of antioxidant properties in red amaranth and red lettuce

We are grateful to Sarah Auld for technical support.Peer reviewe

Assessing the intestinal permeability and anti-inflammatory potential of sesquiterpene lactones from chicory

Funding: This research and the article processing cost were funded by EU Horizon 2020 research & innovation programme under grant agreement N. 760891 project CHIC. M.S.M. also acknowledges the financial support from Fundação para a Ciência e Tecnologia for her PhD scholarship (SFRD/BD/145551/2019).Cichorium intybus L. has recently gained major attention due to large quantities of health-promoting compounds in its roots, such as inulin and sesquiterpene lactones (SLs). Chicory is the main dietary source of SLs, which have underexplored bioactive potential. In this study, we assessed the capacity of SLs to permeate the intestinal barrier to become physiologically available, using in silico predictions and in vitro studies with the well-established cell model of the human intestinal mucosa (differentiated Caco-2 cells). The potential of SLs to modulate inflammatory responses through modulation of the nuclear factor of activated T-cells (NFAT) pathway was also evaluated, using a yeast reporter system. Lactucopicrin was revealed as the most permeable chicory SL in the intestinal barrier model, but it had low anti-inflammatory potential. The SL with the highest anti-inflammatory potential was 11β,13-dihydrolactucin, which inhibited up to 54% of Calcineurin-responsive zinc finger (Crz1) activation, concomitantly with the impairment of the nuclear accumulation of Crz1, the yeast orthologue of human NFAT.publishersversionpublishe

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis

We acknowledge Rita Ramos for support with qRT-PCR and Regina Menezes for the selection of primers; Antonio Temudo and Ana M. Nascimento for imaging support; The IMM-JLA Flow Cytometry Facility. We also thank Prof. Kuninori Suzuki (Tokyo Institute of Technology, Yokohama, Japan) for the 2xmCherry-ATG8 plasmid. TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain. This work was supported by Fundacao para a Ciencia e Tecnologia [iNOVA4Health: UID/Multi/04462/2013, SFRH/BD/73429/2010 and IMM/BI/78-2017 to DM, SFRH/BD/86584/2012 to IF, IF/01097/2013 to CNS, SFRH/BPD/35767/2007 and SFRH/BPD/101646/2014 to ST]. BacHBerry FP7 KBBE-2013-7 613793 to CNS, DM and CJ, Marie Curie International Reintegration Grant and an EMBO Installation Grant to TFO. TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain. The author(s) would like to acknowledge the STSM to AFA and networking support by the COST Action FA 1403 POSITIVe (Interindividual variation in responseto consumption of plant food bioactives and determinants involved), supported by COST (European Cooperation in Science and Technology).Parkinson's disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action. This constitutes a challenge for the development of (poly)phenol-based nutritional therapies. Here, we subjected (poly)phenols from Arbutus unedo to in vitro digestion and tested the products in cell models of PD based on the cytotoxicity of aSyn. The (poly)phenol-digested metabolites from A. unedo leaves (LPDMs) effectively counteracted aSyn and H2O2 toxicity in yeast and human cells, improving viability by reducing aSyn aggregation and inducing its clearance. In addition, LPDMs modulated pathways associated with aSyn toxicity, such as oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial impairment, and SIR2 expression. Overall, LPDMs reduced aSyn toxicity, enhanced the efficiency of ER-associated protein degradation by the proteasome and autophagy, and reduced oxidative stress. In total, our study opens novel avenues for the exploitation of (poly)phenols in nutrition and health.publishersversionpublishe

Differences in the diagnosis and management of systemic lupus erythematosus by primary care and specialist providers in the American Indian/Alaska Native population

Objectives The objective of this study is to investigate differences in the diagnosis and management of systemic lupus erythematosus (SLE) by primary care and specialist physicians in a population-based registry. Methods This study includes individuals from the 2009 Indian Health Service lupus registry population with a diagnosis of SLE documented by either a primary care provider or specialist. SLE classification criteria, laboratory testing, and medication use at any time during the course of disease were determined by medical record abstraction. Results Of the 320 individuals with a diagnosis of SLE, 249 had the diagnosis documented by a specialist, with 71 documented by primary care. Individuals with a specialist diagnosis of SLE were more likely to have medical record documentation of meeting criteria for SLE by all criteria sets (American College of Rheumatology, 79% vs 22%; Boston Weighted, 82% vs 32%; and Systemic Lupus International Collaborating Clinics, 83% vs 35%; p &lt; 0.001 for all comparisons). In addition, specialist diagnosis was associated with documentation of ever having been tested for anti-double-stranded DNA antibody and complement 3 and complement 4 ( p &lt; 0.001). Documentation of ever receiving hydroxychloroquine was also more common with specialist diagnosis (86% vs 64%, p &lt; 0.001). Conclusions Within the population studied, specialist diagnosis of SLE was associated with a higher likelihood of having SLE classification criteria documented, being tested for biomarkers of disease, and ever receiving treatment with hydroxychloroquine. These data support efforts both to increase specialist access for patients with suspected SLE and to provide lupus education to primary care providers. </jats:sec

Neuroprotective effects of digested polyphenols from wild blackberry species

Abstract Purpose Blackberry ingestion has been demonstrated to attenuate brain degenerative processes with the benefits ascribed to the (poly)phenolic components. The aim of this work was to evaluate the neuroprotective potential of two wild blackberry species in a neurodegeneration cell model and compare them with a commercial variety. Methods This work encompasses chemical characterization before and after an in vitro digestion and the assessment of neuroprotection by digested metabolites. Some studies targeting redox/cell death systems were also performed to assess possible neuroprotective molecular mechanisms. Results The three blackberry extracts presented some quantitative differences in polyphenol composition that could be responsible for the different responses in the neurodegeneration cell model. Commercial blackberry extracts were ineffective but both wild blackberries, Rubus brigantinus and Rubus vagabundus, presented neuroprotective effects. It was verified that a diminishment of intracellular ROS levels, modulation of glutathione levels and activation of caspases occurred during treatment. The last effect suggests a preconditioning effect since caspase activation was not accompanied by diminution in cell death and loss of functionality. Conclusions This is the first time that metabolites obtained from an in vitro digested food matrix, and tested at levels approaching the concentrations found in human plasma, have been described as inducing an adaptative response