Mini-dissertation submitted in partial compliance with the requirements for the Master’s Degree in Technology: Homoeopathy in the Department of Homoeopathy, Durban University of Technology, 2011. / The aim of this study was to determine the effect that Curcuma longa 30CH would have on healthy individuals, and record the particular signs and symptoms produced. These signs and symptoms determine the therapeutic indications of this remedy, so that it may be prescribed according to the homoeopathic Law of Similars. The second aim of this study was to analyse the symptomatology of Curcuma longa 30CH in relation to a Doctrine of Signatures analysis of the Curcuma longa plant, in order to facilitate a more comprehensive understanding of the materia medica of this substance. Design The homoeopathic proving of Curcuma longa in 30CH potency took the form of a double blind, randomized, placebo controlled trial. Thirty healthy provers were selected on the basis of them meeting with the necessary inclusion criteria (Appendix A). The provers were randomly divided into 2 groups, of which 20% (6 of the 30 provers) formed the placebo group and received non-medicated powders, and the remaining 80% (24 of the 30 provers) received medicated powders (verum). The 2 groups were not aware of the nature of the substance that they were proving or the potency used. The provers recorded their mental, physical and emotional states over a period of a week prior to taking the remedy in order to establish a baseline for comparison after the administration of the remedy. Both verum and placebo were dispensed in the form of 6 powders. Each powder was taken sublingually 3 times daily for 2 days or until the prover experienced the onset of any symptoms. Each prover kept a journal and recorded their proving signs and symptoms daily after administration of the remedy or the placebo. The data was collected and extracted from these journals and then assessed by the researcher for suitability to be included in the materia medica of Curcuma longa. All data gathered from the case histories (Appendix C), physical examinations and group discussions were also considered for inclusion. Results A variety of mental, emotional and physical symptoms were produced and included in the materia medica of Curcuma longa. There were a total number of 202 symptoms that were produced as a result of the remedy, which resulted in the formulation of 141 rubrics. The main mental and emotional symptoms that surfaced during the proving were depression, a deep sadness, changeability of moods, courage/confidence, relaxed/ calm and less anger, agility, increased concentration, and vivid dreams. The physical symptoms noted were diarrhea, change in energy levels (too much or too little energy), burning sensations, headaches, heart palpitations and increased breathing rates. The symptoms that came about during the proving clearly showed correlation and association with the nature and description of the Turmeric plant, this is in keeping with findings of previous provings (Pistorius, 2006; Webster, 2002; Speckmeier, 2008 & Pather, 2009), furthermore as suggested by Richardson-Boedler (1999:173) the Doctrine of Signatures analysis of the Turmeric plant facilitated in the interpretation of the proving symptoms and thus the materia medica of the remedy.

published_or_final_version / Surgery / Master / Master of Philosophy

Este trabalho teve como objetivo estudar o potencial do uso de farelo obtido do resíduo da extração do pigmento de cúrcuma (Cúrcuma longa L.) na elaboração de filmes biodegradáveis. Primeiramente, foi conduzido um estudo da extração de corante de cúrcuma por método Soxhlet para simular o processo industrial, dessa forma, utilizaram-se dois tipos de solventes, etanol: isopropanol (1:1) e metanol: acetona (1:1). A partir das tortas foi feito um processo de moagem e peneiragem na tentativa de isolar o amido presente, apesar de não ter obtido sucesso, este processo permitiu obter diferentes frações de farelo de cúrcuma. As frações foram divididas em 80 (F1), 200 (F2), 270 (F3), 400 (F4) mesh e fração centrifugada (F5). A caracterização das tortas de cúrcuma e das frações consistiu em análise da composição centesimal, MEV, difração de raios X e FTIR. A partir destas frações foram elaborados filmes pela metodologia casting. Os filmes foram caracterizados por MEV, difração de raios X, FTIR, análise antioxidante, propriedades mecânicas, solubilidade em água, umidade e permeabilidade ao vapor de água. Os filmes feitos a partir das frações (metanol:acetona) apresentaram melhores propriedades mecânicas e de barreira do que os feitos a partir da frações (etanol:isopropanol), porém industrialmente o solvente utilizado para a extração do pigmento é o etanol:isopropanol. Assim, o filme elaborado a partir da fração FE2 (200 mesh) (etanol:isopropanol) foi o escolhido para realizar o estudo de otimização do processo de elaboração destes filmes por ter as melhores propriedades mecânicas e de barreira do que os filmes feitos a partir das frações FE3 e FE5 . Para o estudo da otimização foi desenvolvido um planejamento experimental 22 com quatro pontos axiais e três pontos centrais para estudar o efeito da temperatura de aquecimento (Ta) e do pH da solução filmogênica sobre as propriedades mecânicas, umidade, solubilidade e permeabilidade ao vapor de água dos filmes plastificados com glicerol (22 g de glicerol/100 g da fração) e sorbitol (30 g de sorbitol/100 g da fração). Os resultados foram avaliados utilizando a metodologia de superfície de resposta e análise de multi-resposta. As condições ótimas obtidas para obter filmes com melhores propriedades mecânicas e funcionais foram: T=84,7ºC e pH 8,3, para filmes com glicerol e T=87,6ºC e pH 8,5 para filmes com sorbitol. Os filmes com glicerol quando comparados com o sorbitol, apresentaram menor índice de cristalinidade, menor teor de curcuminóides pela análise por HPLC e DPPH. Os filmes de farelo de cúrcuma com sorbitol foram mais resistentes, pouco elongáveis e menos permeáveis ao vapor de água do que filmes elaborados com glicerol. / This work aimed to study the potential of the bran residue obtained from the extraction of the pigment from turmeric (Curcuma longa L.) in the preparation of biodegradable films. The extraction of the turmeric dye was conducted by Soxhlet procedure in orer to simulate the industrial process. Two types of solvents were employed ethanol isopropanol (1:1) and methanol acetone (1:1). The pies were crushed and sieved in an attempt to isolate the starch, but no success was achieved. However, this process yielded different fractions, which ensured better characterization of the material. The fractions were divided into 80 (F1), 200 (F2), 270 (F3) and 400 (F4) mesh subfractions and centrifuged (F5). The analysis of pies and turmeric fraction were characterized by chemical composition, SEM, XRD and spectroscopy. Films were prepared from these fractions by film casting methodology, and were characterized by SEM, X-ray diffraction and FTIR analysis; they were also analyzed in terms of their antioxidant, mechanical, water solubility, moisture permeability, and water vapor properties. The films prepared from fractions (methanol: acetone) showed better mechanical and barrier properties than those prepared from the fractions (ethanol: isopropanol), but industrially the solvent used for the extraction of pigment is ethanol: isopropanol. Thus, the film prepared from fractional FE2 (200 mesh) (ethanol: isopropanol) which have the best mechanical and barrier properties than the films prepared from fractions from FE3 and FE5, was chosen for the optimization of the preparation of these films. To this end, we developed an experimental design 22 with four axial points and three focal points, for evaluation of the effect of the heating temperature (Ta) and the filmogenic solution pH on the mechanical properties, moisture, solubility, and permeability to water vapor of the films plasticized with glycerol (22 g fraction glycerol/100 g) and sorbitol (30 g sorbitol/100 g fraction). Results were examined by using response surface methodology and analysis multi-response analysis. The optimum conditions for attainment of films with better mechanical properties and functional characteristics were: T = 84.7 º C and pH 8.3 for films with glycerol, and T = 87.6 ° C and pH 8.5 for films with sorbitol. Compared to films plasticized with sorbitol, the films containing glycerol, had lower crystallinity index, lower content of curcuminoids as verified by HPLC analysis and DPPH. The turmeric bran films plasticized with sorbitol were more resistant, less elongated, and slightly permeable to water vapor compared to films prepared with glycerol.

A cúrcuma tem despertado grande interesse na indústria de alimentos devido as suas propriedades funcionais, dentre elas sua ação antioxidante e antidepressiva. Há vários relatos da atividade antidepressiva de extratos vegetais e suas substâncias ativas. A Organização Mundial da Saúde (OMS) estima que futuramente, a segunda maior causa de comprometimento funcional serão os transtornos depressivos, perdendo somente para as doenças coronarianas. Pesquisas mostram que o estresse crônico moderado e imprevisível (ECMI) é considerado um modelo preditivo para a depressão e que modelos animais são amplamente utilizados em estudos pré-clínicos para avaliação de antidepressivos. Dessa forma, faz-se necessário a investigação sobre as propriedades funcionais da cúrcuma, dentre elas sua atividade antioxidante e testes in vivo para demonstrar as possíveis propriedades antidepressivas desse alimento. Assim este trabalho teve como objetivo avaliar a atividade antioxidante por meio da metodologia de superfície de resposta e a ação antidepressiva da cúrcuma em pó em um modelo animal. Foi constatado que a atividade antioxidante da cúrcuma pelos métodos de DPPH e ABTS, apresentou significativo potencial antioxidante, O tratamento com cúrcuma em animais submetidos ao protocolo de ECMI não ocasionou diminuição do volume cerebral, como ocorreu com os animais submetidos ao ECMI sem tratamento. Além disso foi observada uma possível ação antidepressiva da cúrcuma no teste comportamental de natação forçada, pois os animais do grupo ECMI+ CÚRCUMA, apresentaram menor tempo de imobilidade quando comparados aos animais do grupo ECMI+ VEÍCULO. A cúrcuma não apresentou atividade citotóxica como demonstrado por meio das dosagens de transaminases. Conclui-se neste estudo que, o método de quantificação da atividade antioxidante ABTS obteve valores superiores aos encontrados pelo método DPPH e o tratamento com cúrcuma em animais submetidos ao protocolo de ECMI mostrou-se eficaz para alguns parâmetros. Futuros testes devem ser realizados visando evidenciar essa propriedade antidepressiva por meio de experimentos com um período maior de tempo de tratamento com o composto em estudo. / Turmeric has aroused great interest in the food industry because of their functional properties, among them its antioxidant and antidepressant action. There are several reports of antidepressant activity of plant extracts and their active substances. The World Health Organization (WHO) estimates that in the future, the second leading cause of disability are depressive disorders, second only to coronary heart disease. Research shows that moderate and chronic unpredictable stress (CMS) is considered a predictive model for depression and that animal models are widely used in preclinical studies to evaluate antidepressants. Thus, the research it is necessary on the functional properties of turmeric, among them its antioxidant activity and in vivo to demonstrate the possible antidepressant properties of the feed. So this study was to evaluate the antioxidant activity through the response surface methodology and the antidepressant action of turmeric powder in an animal model. It was found that the antioxidant activity of turmeric by the methods of DPPH and ABTS, showed significant antioxidant potential treatment turmeric in animals submitted to CMS protocol did not cause a decrease in brain volume, as with the animals submitted to CMS without treatment. Also observed was a possible antidepressant action of turmeric in the behavioral test forced swim, because the animals of ECMI + TURMERIC group presented lower immobility time when compared to the animals of ECMI + VEHICLE group. Turmeric showed no cytotoxic activity as demonstrated by means of serum aminotransferase levels. We conclude this study, the method of quantification of antioxidant activity ABTS obtained values higher than those found by the DPPH method and treatment with turmeric in animals submitted to CMS protocol was effective for some parameters. Further tests should be conducted to demonstrate that antidepressant owned by experiments with a greater period of time of treatment with the test compound.

背景及研究目的：據報導薑黃素（curcumin）在阿爾茨海默癥（老年癡呆癥）的動物模型中表現出有效性。這可能與其能阻抑β 澱粉樣蛋白的聚集有關，而β 澱粉樣蛋白正是老年癡呆癥中達成共識的神經毒性物質。然而，薑黃素的水溶性很差，這一弱點直接限制其在作為口服藥物的生物利用度。羥丙基-β-環糊精是一種由七個單糖分子鍵合成的環狀分子，該環具有親水性的外部和疏水性的內部，這一特點使得疏水性藥物可以裝入環糊精分子內部從而提高該藥物的親水性，進而提高藥物的口服吸收率。 / 方法：包合物在50 攝氏度下，由摩爾比為1:2 的薑黃素和羥丙基-β-環糊精經過6 小時的攪拌而形成。其后对包合物的物化性質與相同摩爾比的薑黃素與羥丙基-β-環糊精的混合物的物化特性进行了对比以证实包合物的形成，诸如水溶性，掃描電鏡下的形態以及傅利葉紅外圖譜特性。接著用經包合物和普通薑黃素粉末喂食的SD 大鼠做藥代動力學研究，取出大鼠血樣然之後用高效液相色譜-質譜聯用法對薑黃素進行定量，計算出達峰時間（T{U+2098}{U+2090}{U+2093} ）， 峰濃度（C{U+2098}{U+2090}{U+2093} ）以及 0 到4 小時藥時曲綫下面積 （AUC₀→₄{U+2095} ）從而比較包合物較普通薑黃素是否有優越之處。之後，用Tg2576 轉基因小鼠做短期研究，此种小鼠能過度表達β 澱粉樣蛋白，是一種被廣泛應用于老年癡呆癥相關科研的動物模型，經過連續7 日的喂食之後，對小鼠的β 樣澱粉蛋白進行觀察。進一步，將用能同時過度表達β 樣澱粉蛋白與神經纖維結（NTFs）的Tau/APP 轉基因小鼠做長達兩月的藥效學實驗，在實驗始末配以关联恐惧调件反应测试（CFC）和八臂迷宮（Radial Arm Maze）來對實驗小鼠的記憶失進行定量分析。處死小鼠之後，對β 樣澱粉蛋白與神經纖維結（NTFs）進行定量分析從而確定包合物在藥效學上的優勢。 / 結果：在包合的過程中，大部份的薑黃素被整合到包合物之中。通過傅利葉紅外圖譜和掃描電鏡照片都可以觀察到包合物與混合物的顯著不同。在藥代動力學研究中，普通薑黃素粉末的達峰時間為22 分鐘左右，而包合物是40 分鐘，同時，經過包合，峰濃度也提高了3 倍左右，藥時曲綫下面積提高了2 倍以上。在用Tg2576 進行的為期一周的短期實驗中，觀察不到包合物和普通薑黃素在β 樣澱粉蛋白清除方面有明顯差別，然後通過體內染色卻可以看到經包合物喂食的小鼠腦切片中可以觀察到更多的來自薑黃素的螢光信號。在2 個月的長期實驗中，就关联恐惧调件反应测试和八臂迷宮實驗的結果來看，可以觀察到包合物有更好延遲TAPP 小鼠記憶失過程的趨勢但無顯著性，除此之外，對處死后的小鼠腦部進行分析，其β 澱粉樣蛋白與神經纖維節的含量分析結果也和行為測試具有一致性。 / 結論：用羥丙基-β-環糊精對薑黃素進行包合確實可以通過增加薑黃素的水溶性從而提高其生物利用度，讓更多的薑黃素通過血腦屏障進入大腦進而與β 澱粉樣蛋白進行結合。然後短期實驗無法表明包合物具有β 澱粉樣蛋白清除效應。而長期實驗中行為實驗和處死後大腦分析顯示出較普通薑黃素而言包合物具有有限的優點，如果要證明這一優點確實存在，可能需要更長時間的喂食與另外劑量。 / Background: Curcumin is reported to be an effective treatment in animal models of Alzheimer’s disease (AD), possibly by inhibiting aggregation of amyloid-β peptides, which can be neurotoxic.However, curcumin is poorly soluble in water, limiting its oral bioavailability. Hydroxypropyl-β-cyclodextrin (HP-β-CD), a cyclic oligosaccharide made of seven sugar molecules bound togetherin a ring has a hydrophobic exterior and a hydrophobic interior, within which curcumin can reside, thus increasing the aqueous solubility of curcumin. This study aims to solve the problem of poor water-solubility of curcumin using HP-β-CD. / Method: The inclusion complexes were formed by stirring a suspension of curcumin and HP-β-CD at a molar ratio of 1:2 at 50°C for 6 hr. Physicochemical properties, including watersolubility,morphology under scanning electron microscopy (SEM) and the Fourier Transform Infrared (FTIR) spectrum, varied between the inclusion complex and a physical mixture of the two compounds. The inclusion complex and curcumin powder were fed to Sprague Dawley rats for pharmacokinetic studies, from which blood samples were analyzed using LC/MS/MS, and relevant parameters such as T{U+2098}{U+2090}{U+2093}, C{U+2098}{U+2090}{U+2093} and AUC₀→₄{U+2095} were calculated to study the effect of HP-β-CD on the bioavailability of curcumin. To evaluate the pharmacodynamic effects, Tg2576 mice, which over express amyloid-β, were treated for 7 consecutive days with curcumin powder or inclusion complexes. Further, to examine effects of long-term treatment, Tau/APP mice, a commonly used AD model producing both amyloid-β and mutant tau proteins, were treated for 2 months. Behavior tests were conducted at the beginning and end of the long-term treatment to quantify the memory loss of the mice, and post mortem analyses, including quantification of amyloid-β plaques and neurofibrillary tangles, were performed after sacrificing the mice. / Result: The majority of curcumin was integrated into complexes. FTIR profiles and SEM photographs of complexes displayed significant differences from the physical mixture. In the pharmacokinetic study, the concentration of curcumin in the control group peaked at around 22.5 min, while that of inclusion complexes peaked around 40 min. The maximum concentration of curcumin trebled and the area under the curve from 0 to 4 hours more than doubled. For shortterm treatment in Tg2576 mice, paraffin sections stained with Thioflavin T, a dye detecting amyloid-β plaques, showed no obvious difference between mice treated with curcumin powder or complexes; however brain sections from complex-treated mice had more fluorescence signal from curcumin than did mice treated with curcumin powder. For long-term treatment, in terms of the results of contextual fear conditioning and radial arm maze, there was a trend toward inclusion complexes delaying the memory loss of Tau/APP mice more effectively than curcumin powder. Compared to curcumin powder, complexes tended to reduce the number of plaques and neurofibrillary tangles. / Conclusion: Complexation with HP-β-CD can significantly enhance curcumin bioavailability by increasing its water-solubility, allowing more curcumin to penetrate the blood brain barrier to bind to amyloid-β plaques. However, short-term treatment showed no advantage of inclusion complexes in clearing amyloid-β plaques. The results of behavior tests and post-mortem studies from the 2-month long-term treatment indicated limited superiority of inclusion complexes over curcumin powder. A longer feeding period or altered dosage or both might be necessary to enhance the effect of curcumin inclusion complexes. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Liu, Hao. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 104-117). / Abstracts also in Chinese. / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Overview of Alzheimer’s disease --- p.1 / Chapter 1.1.1 --- The pathological mechanisms of Alzheimer’s disease --- p.2 / Chapter 1.1.2 --- Anti-Alzheimer’s disease drugs --- p.3 / Chapter 1.2 --- Curcumin as a potential anti-AD agent --- p.5 / Chapter 1.2.1 --- Actions of curcumin on Aβ --- p.6 / Chapter 1.2.2 --- Anti-inflammatory and anti-oxidant activities of curcumin in AD --- p.8 / Chapter 1.2.3 --- Activities of curcumin to combat metal toxicity --- p.9 / Chapter 1.3 --- The physicochemical properties of curcumin and limitations of curcumin in clinical usage --- p.12 / Chapter 1.4 --- Cyclodextrin in pharmaceutical usage --- p.18 / Chapter 1.5 --- Aims of the study --- p.23 / Chapter Chapter 2 --- Preparation and characterization of curcumin-HP-β-CD complexes --- p.24 / Chapter 2.1 --- Introduction --- p.24 / Chapter 2.2 --- Phase solubility study --- p.24 / Chapter 2.1.2 --- Preparation of solid complexes --- p.28 / Chapter 2.1.3 --- Characterization of solid complexes --- p.29 / Chapter 2.1.4 --- Previous work on the curcumin HP-β-CD inclusion complex --- p.31 / Chapter 2.2 --- Methodology --- p.33 / Chapter 2.2.1 --- Phase solubility test --- p.33 / Chapter 2.2.2 --- Preparation of curcumin-CD complexes --- p.33 / Chapter 2.2.3 --- Recovery --- p.35 / Chapter 2.2.4 --- Differential solubility --- p.36 / Chapter 2.2.5 --- SEM Studies --- p.37 / Chapter 2.2.6 --- Infrared --- p.37 / Chapter 2.3 --- Results and discussion --- p.38 / Chapter 2.3.1 --- Phase solubility analysis --- p.38 / Chapter 2.3.2 --- Recovery test --- p.40 / Chapter 2.3.3 --- Differential solubility --- p.42 / Chapter 2.3.4 --- SEM study --- p.44 / Chapter 2.3.5 --- Infrared study --- p.45 / Chapter Chapter 3 --- Staining of amyloid plaques in Tg2576 mice after oral administration of curcumin-HP-β-cyclodextrin inclusion complex --- p.47 / Chapter 3.1 --- Introduction --- p.47 / Chapter 3.2 --- In vitro staining of amyloid plaques by thioflavin T and curcumin --- p.49 / Chapter 3.2.1 --- Thioflavin T and curcumin specifically binding to amyloid plaques --- p.49 / Chapter 3.2.2 --- Chemicals --- p.51 / Chapter 3.2.3 --- Method --- p.51 / Chapter 3.3 --- In vivo staining of amyloid plaques after oral administration of curcumin-HP-β-CD inclusion complex --- p.53 / Chapter 3.3.1 --- Animal treatment --- p.53 / Chapter 3.3.2 --- Method --- p.54 / Chapter 3.4 --- Results and discussion --- p.56 / Chapter 3.4.1 --- In vitro staining of amyloid plaques by thioflavin T and curcumin --- p.56 / Chapter 3.4.2 --- In vivo staining of amyloid plaques by curcumin --- p.57 / Chapter 3.4.3 --- Plaque removal effects after short-term feeding --- p.58 / Chapter Chapter 4 --- Pharmacokinetic study of curcumin in Sprague-Dawley (SD) rats after oral administration of curcumin-HP-β-cyclodextrin inclusion complex --- p.61 / Chapter 4.1 --- Introduction --- p.61 / Chapter 4.1.1 --- Previous pharmacokinetic study of curcumin-HP-β-CD inclusion complex --- p.61 / Chapter 4.1.2 --- Previously established LC/MS/MS methods for quantification of curcumin in SD rat plasma sample --- p.62 / Chapter 4.2 --- Development and validation of LC/MS/MS assay --- p.63 / Chapter 4.2.1 --- Chemicals --- p.63 / Chapter 4.2.2 --- Instrumentation and chromatographic conditions --- p.63 / Chapter 4.2.3 --- Preparation of standard solutions --- p.63 / Chapter 4.2.5 --- Validation of the assay method --- p.64 / Chapter 4.3 --- Pharmacokinetic profile of curcumin in SD rats --- p.65 / Chapter 4.3.1 --- Animals --- p.65 / Chapter 4.3.2 --- Animal treatment and blood sampling --- p.65 / Chapter 4.3.3 --- Plasma sample analysis --- p.65 / Chapter 4.3.4 --- Data analysis --- p.66 / Chapter 4.4 --- Result and discussion --- p.67 / Chapter 4.4.1 --- Mass spectrum --- p.67 / Chapter 4.4.2 --- Chromatography and specificity --- p.69 / Chapter 4.4.3 --- Linearity and sensitivity --- p.71 / Chapter 4.4.4 --- Method validation---Precision and accuracy --- p.71 / Chapter 4.4.5 --- Method validation---Liquid-liquid extraction recovery --- p.72 / Chapter 4.4.6 --- Pharmacokinetics parameters --- p.73 / Chapter Chapter 5 --- Long-term effects of curcumin-HP-β-CD inclusion complex on Alzheimer’s disease model mice --- p.79 / Chapter 5.1 --- Introduction --- p.79 / Chapter 5.1.1 --- Tau/APP trangenic mouse --- p.79 / Chapter 5.1.2 --- Memory --- p.80 / Chapter 5.1.3 --- The role of the hippocampus in memory --- p.81 / Chapter 5.1.4 --- Memory task contextual fear conditioning (CFC) --- p.82 / Chapter 5.1.5 --- Memory task radial arm maze (RAM) --- p.83 / Chapter 5.2 --- Methods --- p.85 / Chapter 5.2.1 --- Animal treatment --- p.85 / Chapter 5.2.2 --- Contextual fear conditioning test --- p.85 / Chapter 5.2.3 --- Radial arm maze test --- p.87 / Chapter 5.2.4 --- Post-mortem analysis amyloid plaque removal effects of the curcumin-HP-β-CD inclusion complex --- p.88 / Chapter 5.2.5 --- Post-mortem analysis neurofibrillary tangle removal effects of the curcumin-HP-β-CD inclusion complex --- p.90 / Chapter 5.3 --- Results and discussion --- p.92 / Chapter 5.3.1 --- Mortality of the mice --- p.92 / Chapter 5.3.2 --- Contextual fear conditioning test --- p.93 / Chapter 5.3.3 --- Radial arm maze (RAM) test --- p.95 / Chapter 5.3.4 --- Post-mortem analysis amyloid plaque removal effects of the curcumin-HP-β-CD inclusion complex --- p.97 / Chapter 5.3.5 --- Post-mortem analysis neurofibrillary tangle removal effects of the curcumin-HP-β-CD inclusion complex --- p.99 / Chapter Chapter 6 --- Conclusions and future perspective --- p.100 / Chapter 6.1 --- Conclusions --- p.101 / Chapter 6.2 --- Future perspective --- p.103 / References --- p.104

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2014-09-24T14:14:57Z No. of bitstreams: 2 Reis, Pamela Cristina de Sousa Guardiano.pdf: 1296512 bytes, checksum: 257e678ee16ea253856f4f88bba00934 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Cláudia Bueno (claudiamoura18@gmail.com) on 2014-09-25T11:39:13Z (GMT) No. of bitstreams: 2 Reis, Pamela Cristina de Sousa Guardiano.pdf: 1296512 bytes, checksum: 257e678ee16ea253856f4f88bba00934 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-09-25T11:39:13Z (GMT). No. of bitstreams: 2 Reis, Pamela Cristina de Sousa Guardiano.pdf: 1296512 bytes, checksum: 257e678ee16ea253856f4f88bba00934 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-02-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This study aimed to develop general microcapsules containing turmeric oleoresin and cluster derived from turmeric suspended in canola oil from concentrated whey protein, encapsulating material, and evaluate their antimicrobial activity. Turmeric gained fresh in the municipality of Mara Rosa underwent slicing and dehydration in an oven with air circulation. Obtained as a powder after successive washes with ethanol generated containing the ethanol extract of turmeric oleoresin which was rotaevaporado generating the turmeric oleoresin. This extract was subjected to vacuum filtration in order to remove solid fractions, and this filtration gave a cluster of turmeric. Both the extract containing oleoresin such as agglomerated product obtained by filtration were suspended in canola oil and used as core material for developing microcapsules. The microcapsules obtained had good sphericity concluding that the protein concentrate of whey was a good encapsulating material to the core studied. The microcapsules and free oleoresin extract were taken for analysis of antibacterial activity using agar diffusion test and found that the extract of turmeric oleoresin can be regarded as a potential antimicrobial agent, none of the microcapsules showed antimicrobial activity against fungus, but against the bacteria showed bacteriostatic action. We evaluated the behavior of the microcapsules determining their sorption isotherms, thermal stability and glass transition temperature. Before the study concluded that: the microcapsules oleoresin showed good thermal stability at temperatures that did not exceed 225 ° C, while the turmeric powder had good stability under temperatures slightly higher, up to 250 ° C, and these results do not conclusive, necessitating characterization studies of the patterns. / Este trabalho teve por objetivo geral desenvolver microcápsulas contendo oleorresina de cúrcuma e aglomerado derivado da cúrcuma suspensos em óleo de canola, a partir de concentrado de proteína do soro do leite, material encapsulante, e avaliar a sua atividade antimicrobiana. Cúrcuma in natura adquirida no município de Mara Rosa foi submetida a fatiamento e desidratação em estufa com circulação de ar. Obteve-se um pó que, após sucessivas lavagens com etanol gerou o extrato etanólico contendo oleorresina de cúrcuma que foi rotaevaporado gerando a oleorresina de cúrcuma. Esse extrato foi submetido a uma filtração a vácuo, a fim de se retirar frações sólidas, e obteve-se dessa filtração um aglomerado de cúrcuma. Tanto o extrato contendo oleorresina quanto esse produto aglomerado obtido pela filtração foram suspensos em óleo de canola e utilizados como material de recheio para desenvolvimento de microcápsulas. As microcápsulas obtidas apresentaram boa esfericidade concluindo que o concentrado proteico do soro de leite constituiu um bom material encapsulante para o núcleo estudado. As microcápsulas e o extrato de oleorresina livre foram levados para análise de atividade antibacteriana através de teste de difusão em ágar e concluiu-se que o extrato de oleorresina de cúrcuma pode ser tido como um agente antimicrobiano em potencial; nenhuma das microcápsulas apresentou ação antimicrobiana contra o fungo, mas contra a bactéria apresentaram ação bacteriostática. Foi avaliado também o comportamento das microcápsulas determinando suas isotermas de sorção, estabilidade térmica e temperatura de transição vítrea. Diante do estudo concluiu-se que: as microcápsulas de oleorresina apresentaram boa estabilidade térmica sob temperaturas que não ultrapassassem 225°C; enquanto que as de aglomerado de cúrcuma apresentaram boa estabilidade sob temperaturas um pouco maiores, até 250°C, sendo estes resultados não conclusivos, necessitando-se de estudos de caracterização dos padrões.

Cheung, Kwok Kuen. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 226-263). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Thesis (M.S.)--The University of North Carolina at Greensboro, 2008. / Directed by Nadja Cech; submitted to the Dept. of Chemistry and Biochemistry. Title from PDF t.p. (viewed Apr. 13, 2010). Includes bibliographical references (p. 62-68).

abstract: Curcumin is an active ingredient of Curcuma longa (Turmeric) and is studied extensively for its antioxidant, anti-inflammatory, anti-bacterial, anti-viral, and anti-cancer properties. The purpose of this study was to examine the effects of turmeric on blood glucose and plasma insulin levels. The study utilized a placebo-controlled, randomized cross-over design with participants serving as their own control. Eight glucose tolerant healthy participants completed the full study. Three-weeks washout period was kept in between six-weeks. Prior to the test meal day, participants were asked to eat a bagel with their evening dinner. During the day of the test meal, participants reported to the test site in a rested and fasted state. Participants completed mashed potato meal tests with 500 mg of turmeric powder or placebo mixed in water, followed by 3 weeks of 500 mg turmeric or placebo supplement ingestion at home. During this visit blood glucose finger picks were obtained at fasting, 30, 60, 90, and 120 min post-meal. Blood plasma insulin at fasting and at 30 min after the test meal were also obtained. During week 4, participants reported to the test site in a rested and fasted state where fasting blood glucose finger pricks and blood plasma insulin were measured. During week 5 to 7, participants were given a washout time-period. During week 8, entire process from week 1 to 4 was repeated by interchanging the groups. Compared to placebo, reduction in postprandial blood glucose and insulin response were non-significant after ingestion of turmeric powder. Taking turmeric for 3 weeks had no change in blood glucose and insulin levels. However, taking turmeric powder supplements for 3 weeks, showed a 4.4% reduction in blood glucose. Change in insulin at 30 min were compared with baseline insulin level showing no significant change between placebo and turmeric group. Fasting insulin after 3-weeks consumption of turmeric did not show any significant change, but showed a larger effect size (0.08). Future research is essential to examine the turmeric powder supplement benefits over a long period of time in healthy adults and whether it is beneficial in preventing the occurrence of type 2 diabetes. / Dissertation/Thesis / Masters Thesis Nutrition 2017

Submitted by Izabel Franco (izabel-franco@ufscar.br) on 2016-09-14T17:46:21Z No. of bitstreams: 1 DissLMS.pdf: 2276370 bytes, checksum: ee5f91507ba780836a4577a021cc883c (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-16T19:21:04Z (GMT) No. of bitstreams: 1 DissLMS.pdf: 2276370 bytes, checksum: ee5f91507ba780836a4577a021cc883c (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-16T19:21:11Z (GMT) No. of bitstreams: 1 DissLMS.pdf: 2276370 bytes, checksum: ee5f91507ba780836a4577a021cc883c (MD5) / Made available in DSpace on 2016-09-16T19:21:17Z (GMT). No. of bitstreams: 1 DissLMS.pdf: 2276370 bytes, checksum: ee5f91507ba780836a4577a021cc883c (MD5) Previous issue date: 2015-08-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / The Aedes aegypti mosquito is the main responsible for the transmission of dengue. Among numerous alternatives to combat vector, we can cite the use of photosensitizers (PSs) as inactivating of Aedes aegypti larvae. These compounds are able to interact with the light in a specific wavelength, so the cause highly reactive cytotoxic oxygen, resulting in the oxidation of biological targets. The present study had as main objective to analyze the phototoxic effects of PSs: Photogem® and turmeric, in three molecular variations (curcumin, curcuminoids pigment mixture (curcumin, desmethoxycurcumin and bisdemethoxycurcumin) and curcumin in sucrose), against Aedes aegypti larvae under different conditions of delivery of the PSs and lighting. The experiments of this study were divided into two stages: i) Photogem® and the three compositions of turmeric were applied in trials of photodynamic inactivation (PDI) in solution. The groups that received the Photogem®, were also fed with two different types of food, in order to verify the influence of these foods on larval mortality. ii) in a second step the three compositions of turmeric were incorporated in pet food, where it obtained a lyophilized powder, which was subsequently offered to the larvae for scanning. After the receipt of the PSs in solution as in the form of freeze-dried powder, the larvae were irradiated with two sources of light: artificial and natural. In addition to the trials of mortality, other studies were performed, such as checking the time of degradation of PSs when exposed to light, the anatomical location of accumulation of FSs in the larvae, and characterization studies of the product obtained in the form of lyophilized powder. On PDI with the Photogem® comparing the foods, exposed to artificial lighting, one of the foods introduced a higher mortality, indicating the importance of this on effectiveness of PDI. Already on PDI with variations of turmeric, mortality rates varied according to the molecular forms of this compound, showing high mortality for curcumin and curcumin in sucrose. In conditions involving sunlight, high mortality rates were obtained for all FSs delivered solution, featuring in various conditions 100% mortality in 8 hours from exposure to light. For IFD using the freeze-dried powder of three variations of turmeric and sunlight, mortalities in the order of 80% were achieved in lighting 16 hours. The analysis of the fluorescence image obtained by confocal microscope showed that both the three variations of turmeric, such as Photogem®, after an incubation period of 12 hours, accumulated throughout the alimentary canal of the larvae. The Photogem®, as well as turmeric showed potent photodynamic activity being more effective in conditions with higher light intensities. Regarding the delivery conditions of the PS, we observe that the highest values of mortality were obtained through the application of PSs in solution, when compared with the mortality studies using the freeze-dried powder. These results indicate that PDI can be a promising technique in the control of vectors as the Aedes aegypti. / O mosquito Aedes aegypti é o principal vetor responsável pela transmissão da dengue. Dentre as inúmeras alternativas de combate ao vetor, podemos citar o uso de fotossensibilizadores (FSs) como inativadores de larvas do Ae. aegypti. Esses compostos são capazes de interagir com a luz, num comprimento de onda específico, de modo a originar espécies altamente reativas de oxigênio citotóxico, resultando na oxidação de alvos biológicos. O presente estudo teve como principal objetivo analisar os efeitos fototóxicos dos FSs: Photogem® e cúrcuma, em três variações moleculares (curcumina, mistura de pigmentos curcuminóides (curcumina, demetoxicurcumina e bis-demetoxicurcumina) e curcumina em sacarose), contra larvas do Ae. aegypti sob diferentes condições de entrega dos FSs e de iluminação. Os experimentos deste estudo foram divididos em duas etapas: i) tanto o Photogem® quanto as três composições de cúrcuma foram aplicados nos ensaios de inativação fotodinâmica (IFD) em solução. Os grupos que receberam o Photogem® foram também alimentados com dois diferentes tipos de ração, com a finalidade de verificar a influência desses alimentos na mortalidade larval. ii) em uma segunda etapa as três composições de cúrcuma foram incorporadas nas rações, onde obteve-se um pó liofilizado, que foi posteriormente ofertado às larvas para a verificação da mortalidade. Após o recebimento dos FSs, tanto em solução como na forma de pó liofilizado, as larvas foram irradiadas com duas fontes de luz: artificial e natural. Além dos ensaios de mortalidade, outros estudos foram realizados, como a verificação do tempo de degradação dos FSs quando expostos à luz, o local anatômico de acumulação dos FSs nas larvas, e estudos de caracterização do produto obtido na forma de pó liofilizado. Na IFD com o Photogem® comparando as rações, expostas à iluminação artificial, uma delas apresentou uma mortalidade superior, indicando a importância desta na efetividade da IFD. Já na IFD com as variações de cúrcuma, as porcentagens de mortalidade variaram de acordo com as formas moleculares deste composto. Nas condições envolvendo luz solar, foram obtidas altos valores de mortalidade para todos os FSs entregues em solução, apresentando em diversas condições 100% de mortalidade em 8 horas de exposição à luz. Nos ensaios de IFD utilizando o pó liofilizado das três variações de cúrcuma e luz solar, mortalidades da ordem de 80% foram atingidas em 16 horas de iluminação. As análises das imagens de fluorescência obtidas por microscópio confocal mostraram que tanto as três variações de cúrcuma, como o Photogem®, após um período de incubação de 12 horas, acumularam-se em todo o canal alimentar das larvas. O Photogem®, assim como a cúrcuma apresentaram atividade fotodinâmica potente, sendo mais efetivos em condições com maiores intensidades de luz. Com relação às condições de entrega do FS, observamos que as maiores mortalidades foram obtidas através da aplicação dos FSs em solução, quando comparadas com os estudos de mortalidade utilizando o pó liofilizado. Esses resultados indicam que IFD pode ser uma técnica promissora no controle de vetores como o Ae. aegypti.