The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor

The effect of the dietary flavonoid galangin on the metabolism of 7,12-dimethylbenz[a]anthracene (DMBA), the activity of cytochrome P 450 1A1 (CYP1A1), and the expression of CYP1A1 in MCF-7 human breast carcinoma cells was investigated. Galangin inhibited the catabolic breakdown of DMBA, as measured by thin-layer chromatography, in a dose-dependent manner. Galangin also inhibited the formation of DMBA-DNA adducts, and prevented DMBA-induced inhibition of cell growth. Galangin caused a potent, dose-dependent inhibition of CYP1A1 activity, as measured by ethoxyresorufin-O-deethylase activity, in intact cells and in microsomes isolated from DMBA-treated cells. Analysis of the inhibition kinetics by double-reciprocal plot demonstrated that galangin inhibited CYP1A1 activity in a non-competitive manner. Galangin caused an increase in the level of CYP1A1 mRNA, indicating that it may be an agonist of the aryl hydrocarbon receptor, but it inhibited the induction of CYP1A1 mRNA by DMBA or by 2,3,5,7-tetrachlorodibenzo-p-dioxin (TCDD). Galangin also inhibited the DMBA- or TCDD-induced transcription of a reporter vector containing the CYP1A1 promoter. Thus, galangin is a potent inhibitor of DMBA metabolism and an agonist/antagonist of the AhR, and may prove to be an effective chemopreventive agent. © 1999 Cancer Research Campaig

N+3 Aircraft Concept Designs and Trade Studies

Appendices A to F present the theory behind the TASOPT methodology and code. Appendix A describes the bulk of the formulation, while Appendices B to F develop the major sub-models for the engine, fuselage drag, BLI accounting, etc

A Neural Network for Stance Phase detection in smart cane users

Slides from conferencePersons with disabilities often rely on assistive devices to carry on their Activities of Daily Living. Deploying sensors on these devices may provide continuous valuable knowledge on their state and condition. Canes are among the most frequently used assistive devices, regularly employed for ambulation by persons with pain on lower limbs and also for balance. Load on canes is reportedly a meaningful condition indicator. Ideally, it corresponds to the time cane users support weight on their lower limb (stance phase). However, in reality, this relationship is not straightforward. We present a Multilayer Perceptron to reliably predict the Stance Phase in cane users using a simple support detection module on commercial canes. The system has been successfully tested on five cane users in care facilities in Spain. It has been optimized to run on a low cost microcontroller.This work has been supported by: Proyectos Puente and programa operativo de empleo juvenil (UMAJI58) and Plan Propio de Investigación at University of Malaga and the Swedish Knowledge Foundation (KKS) through the research profile Embedded Sensor Systems for Health (ESS−H) at Malardalen University, Sweden. Authors would like to ac- knowledge PONIENTE and LOS NARANJOS senior centers for their support during the tests. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2)

Green tea, mainly through its constituents epigallocatechin gallate, epigallocatechin, epicatechin gallate and epicatechin, has demonstrated anticarcinogenic activity in several animal models, including those for skin, lung and gastro-intestinal tract cancer, although less is known about colorectal cancer. Quercetin, the major flavonoid present in vegetables and fruit, exerts potential anticarcinogenic effects in animal models and cell cultures, but less is known about quercetin glucosides. The objectives of this study were to investigate (i) the antioxidant activity of the phenolic compounds epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside; (ii) the cytotoxicity of different concentrations of epicatechin, epigallocatechin gallate, and gallic acid; (iii) the cellular uptake of epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside and (iv) their effect on the cell cycle. Human colon adenocarcinoma cells were used as experimental model. The results of this study indicate that all dietary flavonoids studied (epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside) show a significant antioxidant effect in a chemical model system, but only epigallocatechin gallate or gallic acid are able to interfere with the cell cycle in Caco2 cell lines. These data suggest that the antioxidant activity of flavonoids is not related to the inhibition of cellular growth. From a structural point of view, the galloyl moiety appears to be required for both the antioxidant and the antiproliferative effects

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe

The effect of Puerariae radix on lipoprotein metabolism in liver and intestinal cells

BACKGROUND: Animal studies investigating the beneficial effects of Puerariae radix on cardiovascular disease have suggested this plant possesses anti-diabetic and lipid lowering properties. However, the exact mechanism by which Puerariae radix affects lipid metabolism is currently unknown. The aim of this study was to investigate the effect of the water extract of Puerariae radix on the secretion of VLDL and chylomicrons from HepG2 liver cells and CaCo2 cells, respectively, in humans. METHODS: The amount of apoB(100 )(a protein marker for VLDL) and apoB(48 )(a protein marker for chylomicrons) in cells and media were quantified by Western Blotting and enhanced chemiluminescence (ECL). Total, free and esterified cholesterol concentrations were measured by gas liquid chromatography. RESULTS: Treatment of cells with water extract of Puerariae radix significantly decreased apoB(100 )production and secretion from HepG2 cells up to 66% in a dose dependent manner. The intracellular total cholesterol and free cholesterol concentration in HepG2 cells also decreased with increasing concentration of the Puerariae radix. In contrast, water extract of Puerariae radix attenuated apoB(48 )concentrations in cells, but not apoB(48 )secretion from CaCo2 enterocytes. CONCLUSIONS: Collectively, our findings suggest that the water extract of Puerariae radix attenuates the hepatic lipoprotein production and secretion. Our present cell culture findings may explain why circulating VLDL and LDL levels were attenuated in animals supplemented with Puerariae radix. Since decreasing the production and secretion of atherogenic lipoproteins decreases the risk of development of cardiovascular disease, diets supplemented with radix may provide a safe and effective beneficial cardioprotective effects in humans

Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets

<p>Abstract</p> <p>Background</p> <p>Flavonoids, a large group of polyphenolic metabolites derived from plants have received a great deal of attention over the last several decades for their properties in inflammation and allergy. Quercetin, the most abundant of plant flavonoids, exerts a modulatory action at nanomolar concentrations on human basophils. As this mechanism needs to be elucidated, in this study we focused the possible signal transduction pathways which may be affected by this compound. Methods: K2-EDTA derived leukocyte buffy coats enriched in basophil granulocytes were treated with different concentrations of quercetin and triggered with anti-IgE, fMLP, the calcium ionophore A23187 and the phorbol ester PMA in different experimental conditions. Basophils were captured in a flow cytometry analysis as CD123bright/HLADRnon expressing cells and fluorescence values of the activation markers CD63-FITC or CD203c-PE were used to produce dose response curves. The same population was assayed for histamine release.</p> <p>Results</p> <p>Quercetin inhibited the expression of CD63 and CD203c and the histamine release in basophils activated with anti-IgE or with the ionophore: the IC50 in the anti-IgE model was higher than in the ionophore model and the effects were more pronounced for CD63 than for CD203c. Nanomolar concentrations of quercetin were able to prime both markers expression and histamine release in the fMLP activation model while no effect of quercetin was observed when basophils were activated with PMA. The specific phosphoinositide-3 kinase (PI3K) inhibitor wortmannin exhibited the same behavior of quercetin in anti-IgE and fMLP activation, thus suggesting a role for PI3K involvement in the priming mechanism.</p> <p>Conclusions</p> <p>These results rule out a possible role of protein kinase C in the complex response of basophil to quercetin, while indirectly suggest PI3K as the major intracellular target of this compound also in human basophils.</p

Apple phytochemicals and their health benefits

Evidence suggests that a diet high in fruits and vegetables may decrease the risk of chronic diseases, such as cardiovascular disease and cancer, and phytochemicals including phenolics, flavonoids and carotenoids from fruits and vegetables may play a key role in reducing chronic disease risk. Apples are a widely consumed, rich source of phytochemicals, and epidemiological studies have linked the consumption of apples with reduced risk of some cancers, cardiovascular disease, asthma, and diabetes. In the laboratory, apples have been found to have very strong antioxidant activity, inhibit cancer cell proliferation, decrease lipid oxidation, and lower cholesterol. Apples contain a variety of phytochemicals, including quercetin, catechin, phloridzin and chlorogenic acid, all of which are strong antioxidants. The phytochemical composition of apples varies greatly between different varieties of apples, and there are also small changes in phytochemicals during the maturation and ripening of the fruit. Storage has little to no effect on apple phytochemicals, but processing can greatly affect apple phytochemicals. While extensive research exists, a literature review of the health benefits of apples and their phytochemicals has not been compiled to summarize this work. The purpose of this paper is to review the most recent literature regarding the health benefits of apples and their phytochemicals, phytochemical bioavailability and antioxidant behavior, and the effects of variety, ripening, storage and processing on apple phytochemicals

Effects of attention on the control of locomotion in individuals with chronic low back pain

<p>Abstract</p> <p>Background</p> <p>People who suffer from low back pain (LBP) exhibit an abnormal gait pattern, characterized by shorter stride length, greater step width, and an impaired thorax-pelvis coordination which may undermine functional walking. As a result, gait in LBP may require stronger cognitive regulation compared to pain free subjects thereby affecting the degree of automaticity of gait control. Conversely, because chronic pain has a strong attentional component, diverting attention away from the pain might facilitate a more efficient walking pattern.</p> <p>Methods</p> <p>Twelve individuals with LBP and fourteen controls participated. Subjects walked on a treadmill at comfortable speed, under varying conditions of attentional load: (a) no secondary task, (b) naming the colors of squares on a screen, (c) naming the colors of color words ("color Stroop task"), and (d) naming the colors of words depicting motor activities. Markers were attached to the thorax, pelvis and feet. Motion was recorded using a three-camera SIMI system with a sample frequency of 100 Hz. To examine the effects of health status and attention on gait, mean and variability of stride parameters were calculated. The coordination between thoracic and pelvic rotations was quantified through the mean and variability of the relative phase between those oscillations.</p> <p>Results</p> <p>LBP sufferers had a lower walking speed, and consequently a smaller stride length and lower mean thorax-pelvis relative phase. Stride length variability was significantly lower in the LBP group but no significant effect of attention was observed. In both groups gait adaptations were found under performance of an attention demanding task, but significantly more so in individuals with LBP as indicated by an interaction effect on relative phase variability.</p> <p>Conclusion</p> <p>Gait in LBP sufferers was characterized by less variable upper body movements. The diminished flexibility in trunk coordination was aggravated under the influence of an attention demanding task. This provides further evidence that individuals with LBP tighten their gait control, and this suggests a stronger cognitive regulation of gait coordination in LBP. These changes in gait coordination reduce the capability to deal with unexpected perturbations, and are therefore maladaptive.</p

Changes in Phospholipid Composition Studied by HPLC and Electric Properties of Liver Cell Membrane of Ethanol-Poisoned Rats

Ethanol introduced into the organism undergoes rapid metabolism to acetaldehyde and then to acetic acid. The process is accompanied by formation of reactive oxygen species (ROS), which damage mainly lipids of membrane cells. The effects of ROS can be neutralized by administering preparations with antioxidant properties. The natural preparations of this kind are teas