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Effects of ellagic acid in human neuroblastoma cellsFjæraa Alfredsson, Christina January 2013 (has links)
A diet rich in polyphenols has been proposed to have beneficial health effects and to reduce risk of disease. Ellagic acid, a polyphenol common in red berries and pomegranates, has potential anti-tumorigenic effects that make it interesting to further study in different cancer cell systems. Neuroblastoma is a childhood cancer that arises during development of the peripheral nervous system. Neuroblastoma, being an embryonal tumor, show loss of function of genes controlling differentiation and apoptosis. Neuroblastoma is a heterogenic tumor disease, and highly malignant neuroblastomas are difficult to treat despite different treatment modalities, identifying a need for new and combinatory treatments. A common model for human neuroblastoma is the SH-SY5Y cell line resembling immature neuroblasts that can be differentiated in vitro with several agents including the phorbol ester 12-O-tetradecanoylphorbol-13-acetate and the vitamin A-derivative all-trans retinoic acid. Here, the effect of ellagic acid on proliferation, cell detachment and apoptosis in non-differentiated and in vitro-differentiated SH-SY5Y cells were studied with the aim of identifying cellular target mechanisms and a possible therapeutic potential for ellagic acid. In non-differentiated cells, ellagic acid reduced cell number, inhibited cell cycle activity, and induced cell detachment and apoptosis. Apoptosis was partly mediated by the intrinsic pathway. 12-O-tetradecanoylphorbol-13-acetate and all-trans retinoic acid both induced morphological differentiation, while only the latter induced G0/G1-arrest. Single-cell analysis revealed that 12-O-tetradecanoylphorbol-13-acetate-treated cells continued cycling during neuritogenesis while these two read-outs were mutually exclusive in all-trans retinoic acid-treated cells. 12-O-tetradecanoylphorbol-13-acetate- and especially all-trans retinoic acid-differentiated cells showed lower sensitivity to ellagic acid-dependent cell detachment and apoptosis. / <p>Artikel 4 ("Altered sensitivity...") ingick som manuskript i avhandlingen, nu publicerad.</p>
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Analysis of cultivable microbiota and diet intake pattern of the long‑lived naked mole‑ratDebebe, Tewodros, Holtze, Susanne, Morhart, Michaela, Hildebrandt, Thomas Bernd, Rodewald, Steffen, Huse, Klaus, Platzer, Matthias, Wyohannes, Dereje, Yirga, Salomon, Lemma, Alemayehu, Thieme, René, König, Brigitte, Birkenmeier, Gerd 29 June 2016 (has links) (PDF)
Background: A variety of microbial communities exist throughout the human and animal body. Genetics, environmental factors and long-term dietary habit contribute to shaping the composition of the gut microbiota. For this reason the study of the gut microbiota of a mammal exhibiting an extraordinary life span is of great importance. The naked mole-rat (Heterocephalus glaber) is a eusocial mammal known for its longevity and cancer resistance. Methods: Here we analyzed its gut microbiota by cultivating the bacteria under aerobic and anaerobic conditions and identifying their species by mass spectrometry. Results: Altogether, 29 species of microbes were identified, predominantly belonging to Firmicutes, and Bacteroidetes. The most frequent species were Bacillus megaterium (45.2 %), followed by Bacteroides thetaiotaomicron (19.4 %), Bacteroides ovatus, Staphylococcus sciuri and Paenibacillus spp., each with a frequency of 16.1 %. Conclusion: Overall, the gut of the naked mole-rat is colonized by diverse, but low numbers of cultivable microbes compared with humans and mice. The primary food plants of the rodents are rich in polyphenols and related compounds, possessing anti-microbial, anti-inflammatory, anti-oxidative as well as anti-cancer activity which may contribute to their exceptionally healthy life.
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Evaluation of pressure- and electrodriven separation techniques for the determination of phenolic compounds in wineDe Villiers, A. J. (Andre Joubert) 03 1900 (has links)
Thesis (MSc)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: The phenolic content of wine is responsible for determining characteristics such as the
organoleptic qualities, colour stability, ageing properties and health-beneficial effects
associated with wine. The aim ofthis study was to investigate the possibilities offered by
capillary electrophoresis (CE) as an alternative separation technique to high performance
liquid chromatography (HPLC) for the analysis of polyphenols in wine. The complexity
of wine samples was the cause that neither technique was capable of a satisfactory singlestep
analysis of wine. Suitable sample preparation techniques such as Sephadex- and Sep-
Pak fractionation and ether extraction of wine polyphenols were investigated. These
techniques did not, however, prove to be universal. A novel form of sample preparation
namely a process analogous to lyophylization used to separate wine volatiles from nonvolatiles
was introduced.
The versatility of CE was further investigated in an attempt to eliminate the need for
sample preparation. The use of polyvinylalcohol (PVA) coated capillaries, micellar
electrokinetic chromatography (MEKC) and capillary gel electrophoresis (CGE) were
investigated in this regard. Although none of these techniques could offer conclusive
results, useful applications were forthcoming and routes for further investigation were
outlined. Liquid chromatography coupled to electro spray ionisation mass spectroscopy
(LC-ESI-MS) and capillary electrophoresis coupled to electro spray ionisation mass
spectroscopy (CE-ESI-MS) were compared for the analysis of polyphenols in wine.
While the latter technique could not produce sufficient separation compared to the
former, future development ofCE-ESI-MS should make it a powerful technique for these
analyses. / AFRIKAANSE OPSOMMING: Die fenoliese komponente in wyn speel 'n bepalende rol by eienskappe soos die
organoleptiese karakter, kleur stabiliteit, verouderingspotensiaal en gesondheids-voordele
wat met wyn geassosieër word. Die doel van hierdie projek was om ondersoek in te stel
na die potensiaal wat kapillêre elektroforese (CE, "capillary electrophoresis") as 'n
alternatiewe skeidingstegniek teenoor hoë druk vloeistof chromatografie (HDVC) vir die
analise van die polifenole in wyn bied. Die kompleksiteit van wyn monsters is van so 'n
aard dat 'n bevredigend enkelstap analise met geeneen van die tegnieke moontlik is nie.
Gepaste monster-voorbereidingstappe soos Sephadex- en Sep-Pak fraksionering asook
eter ekstraksie van die polifenole in wyn is ondersoek. Geeneen van die tegnieke was
egter universeel toepaslik nie. 'n Nuwe metode van monster-voorbereiding, naamlik 'n
proses analoog aan liofilisasie wat gebruik word om die wyn te skei in vlugtige en nievlugtige
komponente is gedemonstreer.
Die veelsydigheid van CE was gevolglik ondersoek in 'n poging om
monstervoorbereiding uit te skakel. Die gebruik van polyvinielalkohol-(pVA) bedekte
kapillêre, missellêre elektrokinetiese chromatografie (MEKC) en kapillêre gel
elektroforese (CGE, "capillary gel electrophoresis) is in hierdie verband ondersoek.
Alhoewel geeneen van hierdie tegnieke onweerlegbare resultate gelewer het nie, het
bruikbare toepassings hieruit voortgespruit en is die grondslag vir verdere navorsing gelê.
Vloeistof chromatografie gekoppel aan eIektrosproei ionisasie massaspektroskopie (LCESI-
MS) en kapillêre elektroforese gekoppel aan elektrosproei ionisasie massaspektroskopie
(CE-ESI-MS) is vergelyk vir die analise van polifenole in wyn. Alhoewel
laasgenoemde tegniek onvoldoende skeiding lewer vergeleke met eersgenoemde, behoort
toekomstige ontwikkelinge op die gebied van CE-ESI-MS dit 'n kragtige tegniek vir die
analise van hierdie monsters te maak.
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Studies on the synthesis of dicaffeoylquinic acid conjugatesRaheem, Kolawole Saki January 2011 (has links)
Dicaffeoylquinic acid (DCQA) is a natural polyphenolic compound widely distributed in plants such as coffee beans, which possesses a range of pharmacological activities. Herein, is reported studies undertaken towards the first total synthesis of 3,5-DCQA conjugates. Two synthetic routes were investigated. The first route involves a seven step sequence beginning from quinic acid. The overall yield via this synthetic approach was 30%. The key steps involved in the sequence were a regioselective benzylation of the C-3-hydroxyl group followed by silyl protection of the C-1 and C-4 hydroxyl groups. Deprotection of the benzyl group by hydrogenolysis and opening of the lactone afforded the 3,5-diol. Esterification of the 3,5-diol with 3,4-tert-butyldimethylsilyl caffeoyl chloride afforded the di-ester. Removal of the protecting groups afforded 3,5-DCQA. The second route involved selective protection of the C-3-hydroxyl group with silyl followed by benzylation of the C-1 and C-3 hydroxyl groups. Saponification of the lactone ring followed by benzylation of the carboxylic acid gave the benzyl ester. Silyl deprotection afforded the 3,5-diol. The 3,5-diol was subsequently esterified by refluxing in toluene with commercially available Meldrum’s acid. In the final step, the synthesis of 3,5-DCQA was achieved by a Knoevenagel condensation of 3,4-dihydroxybenzaldehyde and a malonate ester of quinic acid. An efficient method for the synthesis of possible metabolites of quinic acid conjugates was also described. This protocol employs N-(4-methoxyphenyl)-trifluoroacetimidate glucuronyl as the donor. The key reaction in this sequence was the coupling of N-(4-methoxyphenyl)-trifluoroacetimidate glucuronyl with 4-hydroxy-3-methoxy-benzaldehyde.
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The potential roles of nitric oxide in carbon tetrachloride induced liver injury of mice and the protective effects of green teapolyphenols朱雯, Zhu, Wen. January 1999 (has links)
published_or_final_version / Physics / Doctoral / Doctor of Philosophy
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Curcumin inhibits cell migration of nasopharyngeal carcinoma through reactivation of e-cadherin expressionChan, Wing-san, 陳詠珊 January 2009 (has links)
published_or_final_version / Surgery / Master / Master of Philosophy
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SYNTHESIS AND CHARACTERIZATION OF POLYMERIC ANTIOXIDANT DELIVERY SYSTEMSWattamwar, Paritosh P. 01 January 2011 (has links)
Even though the role of oxidative stress in a variety of disease states is known, strategies to alleviate this oxidative stress by antioxidants have not been able to achieve clinical success. Particularly, treatment of oxidative stress by small molecule antioxidants has not received due attention because of the challenges associated with its delivery. Antioxidant polymers, where small molecule antioxidants are incorporated into the polymer backbone, are an emerging class of materials that can address some of these challenges.
In this work, biodegradable polymers incorporating phenolic antioxidants in the polymer backbone were synthesized. Antioxidant polymers were then characterized for their in vitro degradation, antioxidant release and their effect on oxidative stress levels (redox state) in the cells. Trolox, a water-soluble analogue of vitamin E, was polymerized to synthesize poly(trolox ester) with 100% antioxidant content which undergoes biodegradation to release trolox. Nanoparticles of poly(trolox ester) were able to suppress oxidative stress injury induced by metal nanoparticles in an in vitro cell injury model.
In another study, we polymerized polyphenolic antioxidants (e.g. curcumin, quercetin) using a modified non-free-radical polymerization poly(β-amino ester) chemistry. This synthesis scheme can be extended to all polyphenolic antioxidants and allows tuning of polymer degradation rate by choosing appropriate co-monomers from a large library of monomers available for β-amino ester chemistry. Poly(antioxidant β-amino esters) (PABAE) were synthesized and characterized for their degradation, cytotoxicity and antioxidant activity. PABAE degradation products suppressed oxidative stress levels in the cells confirming antioxidant activity of degradation products.
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An investigation of the photostabilisation of sunscreen absorbers by plant polyphenols.January 2005 (has links)
Commercial sunscreen products are used to protect the skin against hannful ultraviolet (UV) radiation that can induce skin cancer at high dosage. These products contain UV filters that can reflect, scatter or absorb UV light. The chemical UV filters responsible for the absorption of UV radiation can be photochemically modified and as a result reduce the efficacy of the sunscreen formulation. This study focused on the possible use ofplant polyphenols as potential stabilisers of photo-unstable sunscreen chemical absorbers. The photo-instability of some sunscreen absorbers results in radical formation; this prompted the use of the plant, Sutherlandia microphylla (Cancer Bush plant), as a potential photostabiliser. The Cancer Bush plant is used by the indigenous people of South Africa to treat AIDS and cancer. The radical scavenging properties of polyphenolic compounds present in the plant are possibly responsible for the plant's anti-tumour and anti-IDV properties. Therefore, these Cancer Bush polyphenols could possibly be used to photostabilise photo-unstable sunscreen absorbers. Potential polyphenolic photostabilisers from the Cancer Bush plant were extracted by means of various polyphenolic extraction methods. These extracts were analysed by gas chromatography (GC), high-performance liquid chromatography (HPLC), UV spectroscopy and gas chromatography-mass spectrometry (GC-MS). The phenolic content and the antioxidant activity ofthese extracts were investigated by means of the Folin-eiocalteu reagent (FCR) and the diphenylpicrylhydrazyl (DPPH) radical assays respectively. Polyphenols were also extracted from various Rooibos teas and compared with those extracted from the Cancer Bush plant. Both the Cancer Bush and various Rooibos tea extracts were found to contain simple phen~lics and potential polyphenolic compounds. The Cancer Bush extracts as well as the Rooibos tea extracts together with the specific polyphenols, epicatechin and rutin, were assessed for their ability to photostabilise sunscreen absorbers. The photostability of the chemical absorbers in the absence and in the presence of the polyphenol extracts was investigated by UV spectroscopy, by monitoring their absorption spectra during irradiation with solar-simulated radiation. These extracts inhibited the photodegradation of the absorber avobenzone. The photostability of avobenzone is solventIntroduction III dependent hence the investigations were carried out in three solvents, namely, cyclohexane, ethyl acetate and dimethylsulfoxide. Additionally, the cause ofthe instability ofavobenzone in these solvents was investigated by means of DV spectroscopy, HPLC and nuclear magnetic resonance spectroscopy. The oxygen dependency of the photo-instability of avobenzone was also determined. The photo-instability of avobenzone was found to occur as a result of photoisomerisation and!or photodegradation, depending on the solvent. Avobenzone photoisomerised extensively in dimethylsulfoxide and photodegraded appreciably in cyclohexane, whereas both processes occurred to a similar extent in ethyl acetate. Photoisomerisation only occurred in the presence of oxygen whereas photodegradation occurred irrespective of oxygen. The Cancer Bush and various Rooibos tea extracts as well as other polyphenols photostabilised avobenzone in ethyl acetate and dimethylsulfoxide but not in cyclohexane. This photostabilisation effect was potentially due to the radical scavenging ability of polyphenols which prevented the oxygendependent photoisomerisation, but not the oxygen independent photodegradation process from occurring. / Thesis (M.Sc.)-Chemistry-University of KwaZulu-Natal, 2005
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Development of a functional beverage from the Kei apple fruit Dovyalis caffra / M-J. GoreGore, Mary Jane Cook January 2005 (has links)
Interest has grown over the last two decades in the health benefits of polyphenols, with
particular relation to degenerative diseases. The Kei apple (Dovyalis caffra) is an indigenous
plant to South Africa, thought to be rich in polyphenols. This study aimed to produce a
functional beverage from the Kei apple, with demonstrable nutritional benefits, which should
also be found acceptable by consumers due to its sensory attributes. A long term aim of the
study is to assist in improving income of farmers in rural and urban areas by encouraging the
participation of small holders in growing the Kei apple for subsequent economic benefit. A
thorough literature review was conducted on functional foods, trends for beverages, legislation
and on polyphenols as a class of functional ingredients, specifically focusing on fruits and the
fate of polyphenols in the body. A review of fruit processing procedures, preservation
techniques and legislation, followed by new product development (NPD) and the types of
consumers desiring functional foods were investigated as well as the role of sensory evaluation
and consumer research were examined.
Methods
Kei apples were collected from two areas of South Africa, namely Bloemhof in the North West
Province in the 200212003 growing season and from the Eastern and Western Cape in the
200412005 growing season. The first set of Kei apples were used to produce a prototype
functional beverage, from which future development would take place. The second set of Kei
apples were used for pulping on an industrial scale and then a small-scale commercial
production batch of the Kei apple beverages for consumer panel testing was produced.
Various flavours were used to mask the strong characteristic taste and aroma of the Kei apple
for the beverage and these were narrowed down to apple, vanilla and mint 8. vanilla.
Consumer panel testing was undertaken with 152 consumers with a pre-tested questionnaire
using hedonic scales for overall acceptance, ranking for preference, a Fwd Action Rating
Scale (FACT) for consumption intent, and a ranking test for purchase intent. All evaluations
were carried out under strictly controlled sensory evaluation requirement and respondents were
asked to fill in anonymous questionnaires at North West University, Potchefstroom Campus.
Results and Discussion
Statistical analysis of the results were determined by the Statistic* programme, version 7. In
summary for all of the consumer testing, it was found that consumers regarded the apple
flavoured Kei apple beverage statistically significantly more acceptable than the other flavours.
The apple flavoured beverage was found to be rated practically significantly higher for the
attributes of taste and overall acceptance, as well as for consumption intent, purchase intent
and preference. There was, however, no significant differences in any of the attributes or
evaluated consumption and purchase intent between the vanilla and mint & vanilla. The total
polyphenols, determined by UV spectrophotometry as gallic acid equivalents per litre (GAE/I),
were found to be slightly less then expected, with the apple and mint & vanilla showing similar
results (as GAEII) 101.7 versus 106.1 for the latter two, whilst vanilla was 143.0 which may
have been attributed to the vanillic acid molecule itself which also has a phenolic structure.
This lower-than-expected level of total polyphenols may have been due to degradation during
processing. There was a clear difference in the polyphenol content between the different
harvests from the two regions. The former showed greater acidity as determined by total citric
acid 4.81% w/w and sugar 16.3% versus 2.54% w/w and 8.4% This may be due to various
factors of climate, soil and ripeness. For comparison purposes, a commercial product from the
USA, Ocean Spray ® Cranberry, was also found to have more polyphenols present than the Kei
apple beverage. This was also demonstrated by the amount of ascorbic acid, free and bound.
The Kei apple beverage subjected to pasteurization probably lost most of its vitamin C content
due to the heat treatment and the exposure to oxygen during pulping.
Conclusion and Recommendations
The development of a functional beverage from the Kei apple is feasible. As with most new
product developments, further formulation modifications which are not insurmountable are
required. The consumer panel was positive towards the apple flavoured beverage and this
flavour should be taken forward for future development. The key stumbling block to the
success of this project is the lack of an effective organizing body that could liaise with the
growers to form a cooperative and provide a consistent supply of Kei apples. The effect of
variations in harvesting time, soil conditions and climate must also be evaluated. The
improvement of income of farmers may only be achieved by the involvement of other stake
holders and the formation of a Kei apple grower's co-operative / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2006.
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Une approche moléculaire de l'astringence des vins : utilisation de sondes pour l'étude des interactions entre protéines de la salive et polyphénolsDelcambre, Adéline 03 December 2010 (has links)
L’astringence est une sensation de sécheresse ressentie en bouche lors de la dégustation des vins rouges, qui résulte de la complexation entre les polyphénols du vin et les protéines de la salive, provoquant une diminution de lubrification en bouche. Parmi les protéines salivaires, les protéines riches en prolines (PRP) sont connues pour leur capacité à se lier aux polyphénols et à précipiter avec eux. Une meilleure connaissance de ce phénomène au niveau moléculaire est nécessaire pour le comprendre et le maîtriser. Il a été montré qu’un peptide de quatorze acides aminés, IB714, dont la séquence est conservée au sein des protéines riches en proline, était un mime représentatif des PRP. Un travail préliminaire par spectrométrie de masse résolue en énergie a permis de caractériser les interactions entre des polyphénols et le peptide IB714. Une échelle d’affinité en phase gazeuse a ainsi été déterminée. Cependant, cette méthodologie d’analyse d’un système modèle ne permet pas de s’accommoder de la complexité du vin. C’est pourquoi nous avons conçu une nouvelle stratégie reposant sur l'utilisation de sondes moléculaires immobilisée sur des billes magnétiques. Dans un premier temps nous avons élaboré une sonde peptidique, en greffant le peptide IB714 sur des billes magnétiques portant des fonctions carboxylates. Cette sonde peptidique a ensuite été étudiée avec des polyphénols modèles. Après sédimentation des billes magnétiques, les polyphénols non captés par la sonde ont été dosés par spectrométrie de masse en utilisant un étalon interne. Une échelle d'affinité en phase liquide a été établie de cette manière. Les positions relatives des polyphénols modèles sur cette échelle sont similaires à celles qui ont été établies en phase gazeuse. Dans un second temps, nous avons construit sur le même principe une sonde polyphénolique. Pour cela, un polyphénol modifié chimiquement a été immobilisé sur des billes magnétiques portant des fonctions amines. Cette sonde polyphénolique a été utilisée pour étudier l'interaction avec le peptide IB714. Par ailleurs, pour préparer une étude des interactions entre polyphénols et protéines salivaires avec des mélanges plus complexes que les systèmes modèles, une étude de fractionnement des protéines salivaires a été entreprise, permettant notamment de d’éliminer l’amylase, protéine majoritaire de la salive humaine. De même, un fractionnement d’un vin rouge a été entrepris pour disposer de fractions de tannins caractérisées par spectrométrie de masse. La sonde peptidique est l’outil moléculaire qui offre le plus de perspectives de développement ultérieur. / Astringency is a pucker or dry mouth sensation, typically experimented with red wine tasting, that finds its origin in the complexation of polyphenols with salivary proteins, producing a reduced lubrication of the oral cavity. Among salivary proteins, proline rich proteins (PRPs) are well known for their capacity to bind and precipitate dietary polyphenols. A better knowledge of this phenomenon at the molecular level is required in order to master it. A 14 amino acid stretch from the PRP IB7 has been synthesized and shown to be a representative mimic of PRPs. Previous work by Energy Resolved Mass Spectrometry (ERMS) allowed characterizing the keys parameters of the interactions between these polyphenols and the IB714 probe. An affinity scale in the gas phase was determined in this way. However, the ERMS approach was hardly compatible with the complexity of wine polyphenols, and a validation of the affinity scale in condensed phase was required. Thus, we designed a new strategy relying on the use of molecular probes immobilized on magnetic beads. A peptidic probe was obtained by grafting the synthetic IB714 peptide on magnetic beads bearing carboxylate functions, and used to study its interaction with model polyphenols. After magnetic precipitation of the beads, unbound polyphenols left in the supernatant were quantified by mass spectrometry using an internal standard. An affinity scale in liquid phase was established in this way. Relative positions of model polyphenols on this latter scale were similar to those determined by ERMS. A polyphenolic probe was obtained by grafting a model polyphenol on beads bearing amine functions. This probe has been used to study the interaction with IB714. To prepare further work on more complex mixtures, attempts were made to fractionate human saliva; this allowed eliminating amylase, the major salivary protein. Wine tannins were also fractionated, in order to isolate condensed polyphenols that are characterized by mass spectrometry. The peptidic probe is the molecular tool that offers the best perspectives for future work.
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