The aim of this thesis was to evaluate pre-existing methods for isolation and synthesis of curcumin. Two different isolation methods were used, where only the extraction step differs from each other. To obtain pure curcumin, column chromatography was needed to separate the compound from its analogues. As for the isolation the synthesis was also carried out by two different methods, the first in a conventional way and the second one by using irradiation of microwaves. The result of the experiments shows that by comparing the effectiveness and expense of the methods, the synthesis would probably be the easiest way of obtaining pure compound. Because of the more straightforward method, without cumbersome separation steps from the curcumin analogues, the synthesis was a faster way of obtaining the compound and gave more pure curcumin than the isolation procedures from turmeric.

No description available.

The prevalence over overweight and obesity has risen dramatically during the past few decades corresponding with a clustering of metabolic pathologies including cardiovascular disease, type 2 diabetes, endometrial, breast, and colon cancers. Obesity is not only implicated as one of the primary causes of these degenerative diseases but also represents a major component of the metabolic syndrome. In obesity, the primary defect leading to these metabolic pathologies appears to be an impairment of adipogenesis resulting in adipocyte hypertrophy and dysfunction. Current pharmacological therapies prescribed for T2DM, such as thiazolidinones (TZDs), improve insulin sensitivity through regulation of adipogenesis. However, utilization of these drugs is often associated with several side effects, including weight gain, liver disease, and bone loss. Thus, there is an important need to identify alternative therapies that can modify these adipogenic regulators without adverse complications. Ginger (Zingiber officinale Roscoe), a member of the Zingiberaceae family, has a long history of use in traditional medicine and as been used for a wide array of ailments such as arthritis, diabetes, nausea, and stroke. Several studies have demonstrated anti-emetic, anti-inflammatory, and anti-carcinogenic properties of ginger. When used at high concentrations (μM), two phytochemcials derived from ginger root curcumin and zingerone, have been shown to promote weight loss and modify adipogenic signaling. However, due to the low bioavailability of curcumin the physiological relevance of these findings remains to be determined. The purpose of this study was to determine the extent to which curcumin and zingerone modify adipogenesis in 3T3-L1 fibroblasts. To determine the effects of the bioactive components in varying concentrations, 3T3-L1 preadipocytes were exposed to either 100pM, 100nM, or 100μM of curcumin or zingerone and tested for cell viability, lipid accumulation, and PPARγ activation. The results of this study suggest that high concentrations of curcumin (100 μM) may be toxic to 3T3-L1 fibroblasts in vitro and significantly inhibit both cell viability and lipid accumulation. The resultant low PPARγ activity may be attributable to cell necrosis rather than dose-dependent inhibition, suggesting need for further research into extreme curcumin supplementation. While results for zingerone did not differ significantly from vehicle, the results of this study provide evidence that further research is needed to ascertain to what extent curcumin and zingerone dose-dependently modify PPARγ and TCF/LEF in 3T3-L1 fibroblasts using lower physiologically relevant doses.

Orientador: Antônio Wilson Sallum / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-22T14:55:04Z (GMT). No. of bitstreams: 1 Barbosa_VivieneSantana_M.pdf: 2692982 bytes, checksum: 8a2987c554b7ba34f2d70f33080eb9f6 (MD5) Previous issue date: 2013 / Resumo: O objetivo desse estudo foi avaliar, histológica e microbiologicamente, a ação da TFD, da clorexidina a 0,12% (CLX) e do iodo povidine a 10% (PVP-I), na periodontite experimental induzida em ratos. Para isso, 28 ratos Wistar receberam bilateralmente inserção de ligadura ao redor dos primeiros molares inferiores no baseline. Os lados foram aleatoriamente escolhidos para receber só inserção de ligadura (grupo controle) ou ligadura e uma das seguintes terapias: PVP-I a 10% (n=10), CLX a 0,12% (n=8) e TFD (n=10). Cada grupo recebeu o respectivo tratamento em três períodos: 7, 14 e 21 dias após indução da periodontite. Histometricamente, não foi observada diferença estatística na avaliação intergrupo e intragrupo, no que diz respeito à redução da reabsorção óssea alveolar (p>0,05). Histoquimicamente, a avaliação intragrupo mostrou que o grupo TFD apresentou um número menor de células TRAP-positivas/mm quando comparado o lado tratado com o lado não-tratado (p<0,05). No entanto, não houve diferença estatística nos grupos CLX e PVP-I, quando avaliados os respectivos lados que receberam terapia e os lados controle. Na avaliação entre as terapias, não foi possível verificar diferenças significativas na contagem de células TRAP-positivas em todos os grupos avaliados (p>0.05). Na avaliação microbiológica, houve uma redução significativa na carga microbiana nos molares tratados com PVP-I (p=0,03), apontando uma boa efetividade do tratamento. Dentre os molares tratados com CLX, houve uma tendência positiva para redução microbiana através dessa terapia (p=0,10). A TFD apresentou um efeito antimicrobiano apenas em alguns animais, porém sem diferença significativa entre o lado tratado e não tratado (p=0,54). Sendo assim, pode-se concluir que os três agentes mostraram um efeito antimicrobiano sobre os microrganismos totais, porém, como terapia, somente o PVP-I foi eficaz na redução do biofilme bacteriano. No que diz respeito à reabsorção, as três terapias não foram capazes de impedir a reabsorção óssea alveolar nos molares dos ratos ao final dos 21 dias de estudo / Abstract: The aim of this study was to evaluate histologically and microbiologically, the action of PDT, of the chlorhexidine 0.12% (CLX) and povidone iodine 10% (PVP-I) in a experimental rat periodontal disease model. For this purpose, 28 Wistar rats received bilateral ligature in both mandible first molars at baseline. The sides were randomly assigned to receive ligature only (control group) or ligature and one of the following therapies: PVP-I 10% (n=10), chlorhexidine 0.12% (n=8) and PDT (n=10). Each group received their treatment in three periods: 7, 14 and 21 days. Histometrically, no statistical difference was seen in the intragroup and intergroup evaluation, regarding the reduction of alveolar bone resorption (p>0.05). Histochemically, the evaluation intragroup showed that the group of PDT showed a smaller number of cells TRAP-positivas/mm when compared to CLX group (p<0.05). However, there was no statistical difference in the groups CLX and PVP-I, when evaluated the respective sides receiving therapy and control sides. In the evaluation of therapies, it was not possible to verify significant differences in counting TRAP-positive cells in all groups (p> 0.05). In microbiological evaluation, there was a significant reduction in microbial load in molars treated with PVP-I (p=0.03), indicating a good treatment effectiveness. Among the molars treated with CLX, there was a positive trend towards reduction through this therapy (p=0.10). PDT showed an antimicrobial effect only in some animals, but no significant difference between the treated side and untreated (p=0.54). Therefore, one can conclude that the three agents shown an antimicrobial effect on the total microorganisms, however, as the therapy, only the PVP-I was effective in reducing the bacterial biofilm. With respect to absorption, the three treatments were not able to prevent alveolar bone resorption in molars of the rats at the end of the 21 day study / Mestrado / Periodontia / Mestra em Clínica Odontológica

Oxidative stress (OS) and inflammation can be detrimental to exercise performance. Antioxidants such as curcumin are shown to reduce exercise-induced OS, inflammation, muscle damage, and soreness. The purpose of this study was to examine the effect of curcumin on biomarker markers of OS (MDA, TAC), inflammation (TNF-á), muscle damage (CK) and soreness. Participants performed an exercise-induced muscle damage protocol. Before and after supplementation, subjects were randomly assigned to curcumin (1.5 g/day) or placebo for 28 days. Blood was sampled immediately before and after exercise, as well as 60 min, 24, and 48 h after exercise. No significant differences were observed for biomarkers of OS or inflammation. There was a treatment X condition interaction for CK, where CK were significantly lower post supplementation in the curcumin group (p < .0.0001). Curcumin resulted in significantly lower muscle soreness compared to the placebo (p = 0.0120) overall. In conclusion, curcumin may reduce muscle damage, and soreness without affecting the natural OS and inflammatory response to exercise.

No description available.

Oxidative stress is a state characterized by an imbalance between the production and elimination of reactive oxygen species (ROS) within cells. ROS, also known as free radicals, are crucial for cellular signaling and are generated through natural processes. The antioxidant defense system typically regulates their concentrations to prevent oxidative stress-related damage. However, when ROS concentrations surpass a certain threshold and overwhelm the antioxidant defense system, it can lead to physiological issues and impairments in athletic performance. Additionally, oxidative stress and inflammation are closely related phenomena that can exacerbate each other, creating a vicious cycle. Both oxidative stress and inflammation play key roles in the pathophysiology of various chronic conditions such as cardiovascular diseases, neurodegenerative diseases, cancer, diabetes mellitus, autoimmune diseases, and accelerated aging. Furthermore, acute oxidative stress and inflammation have been shown to negatively affect performance by reducing skeletal muscle force output and increasing fatigue. Therefore, it is crucial to explore strategies to mitigate uncontrolled elevations of oxidative stress and inflammation. Curcumin, a bioactive compound found in turmeric, has been linked to antioxidant and anti-inflammatory properties. While cell line and animal studies have demonstrated the antioxidant and anti-inflammatory potential of curcumin, its effects in humans remain inconclusive. This dissertation project aimed to evaluate the effect of a four-week turmeric supplementation intervention on biomarkers associated with exercise-induced oxidative stress and inflammation in recreationally active individuals, 18 to 45 years of age. The study investigated curcumin's potential as an antioxidant and anti-inflammatory agent, while contributing to the existing literature on strategies for managing oxidative stress and inflammation. The findings from this research may offer valuable insights for promoting health, well-being, and athletic performance. / Doctor of Philosophy / Oxidative stress arises from an imbalance between the production and elimination of reactive oxygen species (ROS) within cells. ROS, or free radicals, serve essential roles in cell signaling and are naturally generated. While our bodies possess a defense mechanism that typically regulates ROS concentrations to prevent oxidative stress-related damage, an excess of ROS can overwhelm this system, leading to physiological complications and impairing athletic performance. The interplay between oxidative stress and inflammation exacerbates their effects, initiating a detrimental cycle. Both processes are implicated in chronic ailments such as cardiovascular diseases, Alzheimer's disease, cancer, diabetes mellitus, autoimmune disorders, and accelerated aging. Moreover, elevated concentrations of oxidative stress and inflammation can diminish muscle strength and increase fatigue during exercise. Curcumin, a compound found in turmeric, renowned for its antioxidant and anti-inflammatory properties, presents a potential avenue for managing oxidative stress and inflammation. While some studies have demonstrated these benefits in cellular and animal models, the efficacy of curcumin in humans remains uncertain. This study assessed whether a four-week regimen of turmeric supplementation can attenuate markers of oxidative stress and inflammation in physically active individuals, 18 to 45 years of age. By investigating the potential antioxidant and anti-inflammatory properties of curcumin, this research aimed to contribute novel insights into strategies for mitigating oxidative stress and inflammation, thereby promoting health, well-being, and athletic performance.

Tsang Kwai Fan. / Thesis submitted in: December 2003. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 85-101). / Abstracts in English and Chinese. / Abstracts --- p.i / 摘要 --- p.iii / Acknowledgements --- p.v / Table of Abbreviations --- p.vi / Table of Contents --- p.vii / Chapter Chapter One: --- Introduction of Curcumin / Chapter 1.1 --- What is curcumin? --- p.1 / Chapter 1.2 --- Chemistry of curcumin --- p.2 / Chapter 1.3 --- History of using turmeric --- p.3 / Chapter 1.4 --- Curcumin in biological system --- p.4 / Chapter 1.5 --- Current researches on curcumin --- p.7 / Chapter 1.6 --- Curcumin Toxicity --- p.13 / Chapter Chapter Two: --- Introduction of Muscle Regeneration / Chapter 2.1 --- Reasons for studying muscle regeneration --- p.15 / Chapter 2.2 --- Skeletal muscle: functions and structure --- p.16 / Chapter 2.3 --- Muscle healing process --- p.17 / Chapter 2.4 --- Muscle formation --- p.31 / Chapter 2.5 --- Current trends in enhancing muscle regeneration --- p.37 / Chapter Chapter Three: --- Methodology / Chapter 3.1 --- Animals --- p.41 / Chapter 3.2 --- Histology --- p.42 / Chapter 3.3 --- Measurement of cross-sectional area of muscles --- p.42 / Chapter 3.4 --- Two-dimensional electrophoresis --- p.43 / Chapter 3.5 --- Protein identification by matrix-assisted laser desorption time-of-flight (MALDI-TOF) --- p.47 / Chapter 3.6 --- Cell culture --- p.50 / Chapter 3.7 --- In vitro cell proliferation assay / Chapter 3.8 --- In vitro differentiation assay --- p.51 / Chapter 3.9 --- Transfection and Secreted Alkaline Phosphatase (SEAP) reporter assay --- p.52 / Chapter Chapter Four: --- Results / Chapter 4.1 --- Effects of curcumin on muscle regeneration --- p.58 / Chapter 4.2 --- Two-dimensional electrophoresis --- p.59 / Chapter 4.3 --- Effect of curcumin on myogenic cell proliferation --- p.61 / Chapter 4.4 --- Effect of curcumin on myogenic cell differentiation --- p.61 / Chapter 4.5 --- Signal transduction --- p.63 / Chapter 4.6 --- Legends and table --- p.65 / Chapter Chapter Five: --- Discussion --- p.77 / Chapter Chapter Six: --- Conclusions --- p.84 / References --- p.85 / Appendices --- p.102

The present study was carried out to examine the chemopreventive effects of curcumin and green tea polyphenols on the hamster cheek pouch carcinogenesis model. This model of oral carcinogenesis has been widely used in chemoprevention studies, however, these studies have been limited to the use of DMBA as the carcinogenic agent. We have developed a protocol of carcinogenesis in the hamster cheek pouch using B[a]P, a broadly distributed environmental carcinogen, formed as a by-product of the combustion of organic materials including cigarette smoke. B[a]P- induced tumors in the hamster cheek pouch are primarily endophytic squamous cell carcinomas that closely resemble squamous cell carcinomas of the human oral mucosa. The cheek pouch of male Syrian hamsters were treated topically for eight weeks with 0.6% curcumin, 6.0% curcumin, 2.5% green tea polyphenols, or 5.0% green tea polyphenols, 3 times per week 30 minutes prior to the application of 2.0% B[a]P. The animals were sacrificed 24 hours and 72 hours after the last treatments. Short-term mechanistic markers of malignant progression were used to determine effects of each compound. Cellular proliferation, assessed by bromodeoxyuridine (Brdu) incorporation, p53 protein accumulation, and apoptotic activity were evaluated. The results of the present study demonstrated that 0.6% curcumin and 2.5% green tea polyphenols had strong inhibitory effects on cellular proliferation and p53 protein accumulation. And 6.0% curcumin and 5.0% green tea polyphenols appeared to induce apoptosis. Our data suggest that curcumin and green tea polyphenols may have a plausible chemopreventive effect on oral carcinogenesis in the hamster cheek pouch model.

This thesis includes three stages of experiments. The goal of the thesis was to prepare nanoparticle-encapsulated curcumin for the purpose of drug delivery. The first step was the nanoparticle preparation. The self-assembly of block copolymer (poly(ε- caprolactone)-b-poly(ethylene oxide)) and curcumin was conducted on a gas-liquid two phase microfluidic reactor. During preparation, various chemical parameters and flow rates were tested. The nanoparticles showed flow variability; the size decreased and the loading efficiency increased with increased flow rates. Increasing the water content and drug-to-polymer loading ratio also proved to increase loading efficiency and decrease the size of the nanoparticles. The release profiles, however, showed fast release rates under various preparation conditions, with a nearly complete release after ~5 h. In the next stage of the research, we considered release optimization in preparation for future pharmacokinetic studies. Increasing the flow rate had a greater influence on slowing down release rates than changing other parameters, such as decreasing the drug-to- polymer loading ratio or increasing the water content. A procedure to extract and quantify curcumin from mouse blood was also developed in this stage. In the final stage of the research, nanoparticle-encapsulated curcumin was tested on a human breast cancer cell line, MDA-MB-231. The result showed that the nanoparticle formulation had a growth inhibition effect on MDA-MB-231, although the cytotoxicity was compromised by encapsulation in the nanoparticles. / Graduate / 2019-01-13