Curcumin, a polyphenol, has been suggested to improve metabolic byproduct clearance and increase nitric oxide production in working muscle. These purported effects may delay neuromuscular fatigue. Therefore, the purpose of this study was to examine the effects of curcumin in combination with fenugreek (CUR) or fenugreek soluble fiber alone (FEN) on the neuromuscular fatigue threshold (PWCFT), time to exhaustion (Tlim) on a graded exercise test (GXT), and O2peak in untrained subjects.Forty-seven,college-aged, aerobically untrained individuals were randomly assigned to one of three supplementation groups; placebo (PLA, n=15),curcumin + fenugreek, CurQfen® (CUR, n=18), or fenugreek soluble fiber (FEN, n=14). All subjects performed a maximal GXT on a cycle ergometer to determine the PWCFT, Tlim, and O2peak before (PRE-test) and after (POST-test) 28 days of daily supplementation. Statistical analyses included 3 separate, one-way ANCOVAs to determine if there were any differences among the groups (PLA, CUR, FEN) for adjusted post-test scores for the PWCFT, O2peak, and Tlim. The respective pre-test score was used as the covariate. In addition, reliability analyses (PRE- to POST-test) for the PLA group were used to calculate the minimal difference needed to be real (MD). The adjusted POST PWCFTvalues showed no statistical differences between groups (F= 3.141p= 0.053); however pairwise LSD comparisons indicated a significant difference between the CUR and PLA groups (p= 0.016), but not between the CUR and FEN groups. Therefore, separate one-way ANCOVAs were used to examine the adjusted PWCFTmeans for the PLA vs. CUR (F = 4.906, p =0.035) and the PLA vs. FEN (F = 2.969, p = 0.097). The one- way ANCOVA for O2peak (F= 0.612 p= 0.547) and Tlim(F = 0.688, p = 0.508) values showed no statistical difference among the groups. Individual responses in each group showed ~ 20% of subjects in the CUR group, ~ 7% in the FEN group, and ~6% in the PLA group had values greater than the MD for the PWCFT, but none of the subjects in the PLA, FEN, or CUR groups exceeded the MD for O2peak or Tlim. These findings indicatedCurQfen® supplementation increased the PWCFTcompared to a placebo, but not compared to fenugreek soluble fiber alone. However, there were no effects of CurQfen® on O2 peak or Tlim. The mechanisms responsible for delaying time to neuromuscular fatigue may include increased NO production and increased blood flow to remove metabolic byproducts; however, the cellular changes which could lead to increases in Tlim andO2peak may not have been sensitive to the GXT protocol or the given dosage of curcumin supplementation. Considering individual responses, CurQfen® supplementation resulted in a real change in the PWCFTfor a small portion of the subjects (~20%). These findings suggested that CurQfen® supplementation without exercise training may help to improve time to neuromuscular fatigue in certain individuals, but the group mean analyses were not necessarily reflective of the responses for a majority of the subjects.

The brain is capable of plasticity, so that the structural and functional loss that are caused by cortical injury may recover. Neuroinflammatory response can greatly influence post-injury recovery by modulating synaptic plasticity. In our previous work, mesenchymal derived exosomes were found to promote functional recovery by converting microglia from a pro-inflammatory state to an anti-inflammatory state in aged rhesus monkeys after cortical injury in the primary motor cortex. In the present project, we demonstrated the effects of exosomes on synaptic changes and synapse-microglia interactions after lesion in the same monkeys. To further investigate the effects of modulating neuroinflammation on synaptic changes after injury, we also investigated dietary curcumin, an anti-inflammatory substance, in a separate group of monkeys. Both treatments showed an effect as neuroinflammatory modulators that reduced the density of microglial markers, Iba- 1/P2RY12. However, the cortical injury induced synaptic loss was reversed by the exosome treatment, whereas the other anti-inflammatory treatment, curcumin, did not show the same effect. Our results are consistent with previous study that cortical injury induced synaptic loss and microglia activation. Exosomes can both reduce inflammation and synapse loss after injury, but curcumin only showed anti-inflammatory effects. Overall, these data suggested that exosomes and curcumin had different mechanisms of how to modulate inflammation and synaptic properties to promote recovery after cortical injury.

PROBLEM: Colorectal cancer (CRC) is a top three leading cause of death among western countries. Epidemiological evidence shows a positive correlation between western diet, which consists of high-fat, meat and processed foods. Positive correlations indicate that diets high in fruits and vegetables could greatly decrease risk of CRC. Specifically the ubiquitous spice, turmeric, and its main active constituent have been broadly researched to determine its efficacy in the treatment and prevention of CRC. RESULTS: Curcumin proves to be effective in the treatment and prevention of CRC. It acts as a chemosensitizer for chemotherapeutics which increases their effectiveness especially against chemoresistant CRC cell lines. In many in vitro studies curcumin has inhibited critical pathways involved in CRC progression such as Wnt/β-catenin and sonic hedgehog pathway. Curcumin can also act as a ligand for VDR, which is significant because high vitamin D intake is associated with a decreased risk of CRC. In vivo, curcumin has minimized tumor growth in animal models. In clinical trials curcumin proves to be a naturally derived, non-toxic agent. CONCLUSION: Curcumin and turmeric should be further studied for its use against CRC, specifically its use in nanotechnology and NDDS as either a stand-alone nutraceutical or a chemosensitizer. Additionally, it would likely be advantageous to prescribe turmeric in the diet in combination with black pepper, heat, and oil (which increases its bioavailability) in patients at high risk of developing CRC.

京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第21699号 / 医科博第103号 / 新制||医科||7(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 妹尾 浩, 教授 渡邊 直樹, 教授 松原 和夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Turmeric polar extract (TPE) was obtained by dielectric-precipitation of turmeric slurry and found to contain three proteins with two in the 10-11 KDa range being dominant. Antioxidative activity and persistence (AP) of TPE (5%, w/v) respectively showed 87% and 85% greater generation of alkoxy- and peroxyl radicals compared the non-redox-active buffer alone showing significant (p<0.05) pro-oxidative behavior. Conversely, purified curcumin (CU) (0.1% w/v) was dramatically antioxidative with AA and AP values of 2,828 and 1,129%, respectively, compared to the blank. However, a combination of the two at the same concentration dropped these values to 590 and 389%, respectively, reflecting dramatic dampening of the efficacy of CU. Ultraviolet radiation significantly modulated the efficacy of CU where UVB (300 nm) exposure gave the highest enhancement when limited to five min. Data showed that turmeric contains highly pro-oxidant polar proteins that significantly dramatically diminishes the beneficial antioxidative efficacy of its principal phytochemical, CU.

The food-borne pathogen Listeria monocytogenes can attach to the environmental surfaces and develop biofilm which can cause food contamination in the food industries. Sortase A and surface proteins are involved in biofilm and virulence of L. monocytogenes. Curcumin was reported to inhibit sortase A and biofilm in gram positive bacteria. The overall objective of this study was to observe the effect of curcumin (Curcuma longa) on the biofilm formation and surface proteins of L. monocytogenes. The antibiofilm effect of curcumin against the strain LM21 (wild type) and s22-11G (sortase A defective mutant) was studied using the microtiter plate assay. No significant differences between the growth of the wild type and the sortase A defective mutant were observed at sub-inhibitory concentrations of curcumin. However, a greater biofilm reduction was observed in the strain s22-11G. The effect of curcumin from two different manufacturers on the wild type was also compared by the microtiter plate assay. Both curcumin did not exhibit statistically different effect on the growth of the wild type. However, a greater biofilm inhibitory effect was observed in one curcumin. The HPLC results suggested that curcumin with the greater antibiofilm activity contained higher amount of curcumin which was reported to be the most potent curcuminoid compound in curcumin. Three different protein extraction methods were evaluated and the most efficient method was used for 2D-GE. When cells were grown in the presence of curcumin, 5 proteins, 16 proteins and 4 proteins were up-regulated, down-regulated and absent, respectively in L. monocytogenes LM21. The influence of the enzyme sortase A upon surface protein expression was evaluated by comparing proteins expressed by wildtype L. monocytogenes LM21 to that of the sortase A mutant, s22-11G. In strain s22-11G, 2 proteins, 8 proteins and 3 proteins were up-regulated, down-regulated and absent in comparison to wildype LM21. The exact information of these differentially expressed proteins still need to be identified by mass spectrometry.

The functional ingredient curcumin has a variety of biological and pharmacological actions, such as anti-tumor, anti-inflammatory, anti-virus, anti-oxidant, and anti-HIV properties coupled with low toxicity. However, curcumin possesses low bioavailability due to its poor solubility in water. The purpose of this study was to investigate the impact of different lipid-based formulations of curcumin on in vitro solubilization and bioaccessibility. Oils representing LCT, MCT, LCT:SCT mix and SCT were used to prepare O/W (nano)emulsions with droplet sizes as low as 174 nm. An in vitro digestion model simulating the small intestine milieu in the fasted and fed state was used to characterize rate, extent, and particle size associated with emulsion digestion. Rate and extent were oil dependent, but not particle size. SCT emulsions digested at the fastest initial rate, but MCT emulsions were digested to the largest extent. Bioaccessibility, a precursor to eventual bioavailability, was determined after digestion using a curcumin:lipid content dependent and independent method. MCT produced the highest bioaccessibility of curcumin for each method. Nanoemulsion digestion and bioaccessibility results were compared to conventional emulsions because an appropriate comparison was needed to determine the merits of the nanoemulsion delivery system. There was no significant difference in particle size and bioaccessibility between the conventional and nanoemulsions.

Yes / We report formation of polymorphs and new eutectics and cocrystals of curcumin, a sparingly water-soluble active component in turmeric, structurally similar to cinnamic acid. The curcumin polymorphs were formed using liquid antisolvent precipitation, where acetone acted as a solvent and water was used as the antisolvent. The metastable form 2 of curcumin was successfully prepared in varied morphology over a wide range of solvent-to-antisolvent ratio and under acidic pH conditions. We also report formation of new eutectics and cocrystals of curcumin with cinnamic acid acting as a coformer. The binary phase diagrams were studied using differential scanning calorimetry and predicted formation of the eutectics at the curcumin mole fraction of 0.15 and 0.33, whereas a cocrystal was formed at 0.3 mole fraction of curcumin in the curcumin–cinnamic acid mixture. The formation of the cocrystal was supported with X-ray powder diffraction, the enthalpy of fusion values, Fourier-transform infrared spectroscopy, and scanning electron microscopy. The hydrogen bond interaction between curcumin and cinnamic acid was predicted from Fourier-transform infrared spectra, individually optimized curcumin and cinnamic acid structures by quantum mechanical calculations using Gaussian-09 and their respective unit cell packing structures.

No description available.

A Curcumin há muito tempo é utilizada como condimento, colorífico e na medicina tradicional asiática. Conhecida como açafrão-da-índia, recentemente tem chamado a atenção devido ao grande potencial medicinal. Surgiram trabalhos principalmente sobre seus supostos efeitos benignos no tratamento de câncer e Alzheimer porém não limitados a estas enfermidades. Na tentativa de otimizar as propriedades medicinais surgiu a Dimethoxy Curcumin, um composto sintético que apresenta maior citotoxicidade e estabilidade biológica que a Curcumin. A maioria das reações químicas e biológicas ocorrem em soluções e os efeitos dos solventes são de extrema importância e complexidade. Neste trabalho nós estudamos os efeitos dos solventes ciclohexano e acetonitrila nos espectros de absorção e emissão da Dimethoxy Curcumin. Consideramos a contribuição de diferentes isômeros e estados excitados usando a Teoria do Funcional Densidade Dependente do Tempo (TD-DFT) utilizando a aproximação Modelo Contínuo Polarizável para o solvente. Nós observamos que as energias de emissão dos estados singletos sofrem um deslocamento para o vermelho enquanto que os estados tripletos sofrem um deslocamento para o azul. Respondemos estas questões analisando a variação do momento de dipolo durante a transição. Neste trabalho encontramos boa concordância com os valores experimentais dos espectros de absorção, emissão, deslocamento espectral e deslocamento Stokes. / The Curcumin has long been used as a condiment, pigment and in the traditional Asian medicine. Known as turmeric, recently has attracted attention because of the large medical potential. Several studies were made mainly about the supposed benign effects in the treatment of cancer and Alzheimer but not limited to these diseases. Attempt to optimize their medicinal properties there appeared the Dimethoxy Curcumin, a synthetic compound that has a higher cytotoxicity and biological stability than Curcumin. Most of the chemical and biological reactions occur in solutions and the solvent effects are of great importance and complexity. In the present work, we study the effects of the solvents cyclohexane and acetonitrile in the absorption and emission spectra of Dimethoxy Curcumin. We consider the contribution of various isomers and excited states using the Time Dependent Density Functional Theory (TD-DFT) with the Polarizable Continuum Model (PCM) approximation for the solvent. We observe that the emission energy of the singlet states are red shifted while the triplet states are blue shifted. We address this by analyzing the dipole moment variation after the transition. We find good agreement with the experimental values for the absorption, emission, spectral shift and Stokes shift