Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects

<p>Abstract</p> <p>Background</p> <p>Previous animal studies have shown that <it>Curcuma (C.) longa </it>lowers plasma glucose. <it>C. longa </it>may thus be a promising ingredient in functional foods aimed at preventing type 2 diabetes. The purpose of the study is to study the effect of <it>C. longa </it>on postprandial plasma glucose, insulin levels and glycemic index (GI) in healthy subjects.</p> <p>Methods</p> <p>Fourteen healthy subjects were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with capsules containing a placebo or <it>C. longa</it>. Finger-prick capillary and venous blood samples were collected before, and 15, 30, 45, 60, 90, and 120 min after the start of the OGTT to measure the glucose and insulin levels, respectively.</p> <p>Results</p> <p>The ingestion of 6 g <it>C. longa </it>had no significant effect on the glucose response. The change in insulin was significantly higher 30 min (<it>P </it>= 0.03) and 60 min (<it>P </it>= 0.041) after the OGTT including <it>C. longa</it>. The insulin AUCs were also significantly higher after the ingestion of <it>C. longa</it>, 15 (<it>P </it>= 0.048), 30 (<it>P </it>= 0.035), 90 (<it>P </it>= 0.03), and 120 (<it>P </it>= 0.02) minutes after the OGTT.</p> <p>Conclusions</p> <p>The ingestion of 6 g <it>C. longa </it>increased postprandial serum insulin levels, but did not seem to affect plasma glucose levels or GI, in healthy subjects. The results indicate that <it>C. longa </it>may have an effect on insulin secretion.</p> <p>Trial registration number</p> <p>NCT01029327</p

Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies

&lt;p&gt;Background: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.&lt;/p&gt; &lt;p&gt;Methods and Findings: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.&lt;/p&gt; &lt;p&gt;Conclusions: Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions.&lt;/p&gt

Genital ulcer severity score and genital health quality of life in Behçet's disease

Background: Behçet's Disease (BD) is a chronic auto-inflammatory, multisystem relapsing/remitting disorder of unknown aetiology. Oro-genital ulceration is a key feature of the disease and has a major impact on the patients' quality of life. Other clinical manifestations include ocular inflammation, rheumatologic and skin involvement, while CNS and vascular complications can lead to considerable morbidity. The availability of a valid monitoring tool for BD activity is crucial in evaluating the impact of the disease on daily life activity. The aims of this study were to validate a novel tool for monitoring genital ulceration severity in BD and to assess the impact of genital ulcers on the Genital Health Quality of Life (GHQoL). Methods: Genital Ulcer Severity Score (GUSS) was developed using six genital ulcer characteristics: number, size, duration, ulcer-free period, pain and site. A total of 207 BD patients were examined, (137 females: mean age∈±∈SD: 39.83∈±∈13.42 and 70 males: mean age∈±∈SD: 39.98∈±∈11.95) from the multidisciplinary Behçet's Centre of Excellence at Barts Health NHS Trust. GUSS was used in conjunction with Behçet's Disease Current Activity Form (BDCAF). Results: The over-all score of GUSS showed a strong correlation with all genital ulcer characteristics, and the strongest correlation was with the pain domain (r∈=∈0.936; P∈2: 0.600; P∈<∈0.0001). Conclusions: This study established the practicality of GUSS as a severity monitoring tool for BD genital ulcers and validated its use in 207 patients. Genital ulcers of BD have a considerable impact on the patients GHQoL

Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications

There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications

Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes

<p>Abstract</p> <p>Background</p> <p>Adipocytes express inflammatory mediators that contribute to the low-level, chronic inflammation found in obese subjects and have been linked to the onset of cardiovascular disorders and insulin resistance associated with type 2 diabetes mellitus. A reduction in inflammatory gene expression in adipocytes would be expected to reverse this low-level, inflammatory state and improve cardiovascular function and insulin sensitivity. The natural products, curcumin and resveratrol, are established anti-inflammatory compounds that mediate their effects by inhibiting activation of NF-κB signaling. In the present study, we examined if these natural products can inhibit NF-κB activation in adipocytes and in doing so reduce cytokine expression.</p> <p>Methods</p> <p>Cytokine (TNF-α, IL-1β, IL-6) and COX-2 gene expression in 3T3-L1-derived adipocytes was measured by quantitative real-time PCR (qRT-PCR) with or without TNFα-stimulation. Cytokine protein and prostaglandin E₂(PGE₂) expression were measured by ELISA. Effects of curcumin and resveratrol were evaluated by treating TNFα-stimulated adipocytes with each compound and 1) assessing the activation state of the NF-κB signaling pathway and 2) measuring inflammatory gene expression by qRT-PCR and ELISA.</p> <p>Results</p> <p>Both preadipocytes and differentiated adipocytes express the genes for TNF-α, IL-6, and COX-2, key mediators of the inflammatory response. Preadipocytes were also found to express IL-1β; however, IL-1β expression was absent in differentiated adipocytes. TNF-α treatment activated NF-κB signaling in differentiated adipocytes by inducing IκB degradation and NF-κB translocation to the nucleus, and as a result increased IL-6 (6-fold) and COX-2 (2.5-fold) mRNA levels. TNF-α also activated IL-1β gene expression in differentiated adipocytes, but had no effect on endogenous TNF-α mRNA levels. No detectable TNFα or IL-1β was secreted by adipocytes. Curcumin and resveratrol treatment inhibited NF-κB activation and resulted in a reduction of TNF-α, IL-1β, IL-6, and COX-2 gene expression (IC₅₀= 2 μM) and a reduction of secreted IL-6 and PGE₂(IC₅₀~ 20 μM).</p> <p>Conclusion</p> <p>Curcumin and resveratrol are able to inhibit TNFα-activated NF-κB signaling in adipocytes and as a result significantly reduce cytokine expression. These data suggest that curcumin and resveratrol may provide a novel and safe approach to reduce or inhibit the chronic inflammatory properties of adipose tissue.</p

Electronic structure investigation of a charge density wave coupled to a metal-to-metal transition in Ce3Co4Sn13

We study the electronic structure of the skutterudite Ce3Co4Sn13, which is known to exhibit a charge density wave (CDW) transition, at temperature TCDW∼160 K, coupled to a metal-to-metal transition. We use temperature dependent hard x-ray photoemission spectroscopy (HAXPES) and x-ray absorption spectroscopy (XAS) to investigate the occupied and unoccupied electronic states of Ce3Co4Sn13. The Co 2p and Sn 3p core level spectra show small but finite shifts in binding energy positions across TCDW while Ce 3d core level spectra do not show any change across the transition. The Ce M4,5-edge XAS spectrum compared with calculations indicate a typical trivalent ionic Ce3+ spectral shape, ruling out Kondo screening in Ce3Co4Sn13. In contrast, the Co L2,3-edge XAS spectrum compared with a calculated spectrum shows evidence for hybridization with neighboring Sn atoms in a trigonal prismatic co-ordination. Temperature dependent XAS across the Co L2,3-edge shows a small shift across TCDW, consistent with HAXPES results. Detailed XAS measurements as a function of temperature show that the spectral shifts occur with a hysteresis across TCDW, indicative of a first-order transition. Valence band spectra show a normal Fermi edge above and below TCDW. The Co 3d states are observed at a binding energy of ∼2 eV while the Ce 4f states occur as a weak feature within 0.5 eV of the Fermi level. The results suggest an unusual CDW transition coupled to a metal-to-metal transition in Ce3Co4Sn13

The Wnt-dependent signaling pathways as target in oncology drug discovery

Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways

Health benefits of herbs and spices: the past, the present, the future

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.UnlabelledHerbs and spices have a traditional history of use, with strong roles in cultural heritage, and in the appreciation of food and its links to health. Demonstrating the benefits of foods by scientific means remains a challenge, particularly when compared with standards applied for assessing pharmaceutical agents. Pharmaceuticals are small-molecular-weight compounds consumed in a purified and concentrated form. Food is eaten in combinations, in relatively large, unmeasured quantities under highly socialised conditions. The real challenge lies not in proving whether foods, such as herbs and spices, have health benefits, but in defining what these benefits are and developing the methods to expose them by scientific means.Cultural aspectsThe place of herbs and spices in the diet needs to be considered in reviewing health benefits. This includes definitions of the food category and the way in which benefits might be viewed, and therefore researched. Research may focus on identifying bioactive substances in herbs and spices, or on their properties as a whole food, and/or be set in the context of a dietary cuisine.The role of herbs and spices in healthThe antioxidant properties of herbs and spices are of particular interest in view of the impact of oxidative modification of low-density lipoprotein cholesterol in the development of atherosclerosis. There is level III-3 evidence (National Health and Medical Research Council [NHMRC] levels of evidence) that consuming a half to one clove of garlic (or equivalent) daily may have a cholesterol-lowering effect of up to 9%. There is level III-1 evidence that 7.2 g of aged garlic extract has been associated with anticlotting (in-vivo studies), as well as modest reductions in blood pressure (an approximate 5.5% decrease in systolic blood pressure). A range of bioactive compounds in herbs and spices have been studied for anticarcinogenic properties in animals, but the challenge lies in integrating this knowledge to ascertain whether any effects can be observed in humans, and within defined cuisines. Research on the effects of herbs and spices on mental health should distinguish between cognitive decline associated with ageing and the acute effects of psychological and cognitive function. There is level I and II evidence for the effect of some herbal supplements on psychological and cognitive function. There is very limited scientific evidence for the effects of herbs and spices on type 2 diabetes mellitus, with the best evidence being available for the effect of ginseng on glycaemia, albeit based on four studies. More research is required, particularly examining the effects of chronic consumption patterns. With increasing interest in alternatives to non-steroidal anti-inflammatory agents in the management of chronic inflammation, research is emerging on the use of food extracts. There is level II evidence for the use of ginger in ameliorating arthritic knee pain; however, the improvement is modest and the efficacy of ginger treatment is ranked below that of ibuprofen. More definitive research is required.Public health and dietary implicationsRecommendations for intakes of food in the Australian guide to healthy eating do not yet include suggested intakes of herbs and spices. Future consideration should be given to including more explicit recommendations about their place in a healthy diet. In addition to delivering antioxidant and other properties, herbs and spices can be used in recipes to partially or wholly replace less desirable ingredients such as salt, sugar and added saturated fat in, for example, marinades and dressings, stir-fry dishes, casseroles, soups, curries and Mediterranean-style cooking. Vegetable dishes and vegetarian options may be more appetising when prepared with herbs and spices.Future directionsAs several metabolic diseases and age-related degenerative disorders are closely associated with oxidative processes in the body, the use of herbs and spices as a source of antioxidants to combat oxidation warrants further attention. Immediate studies should focus on validating the antioxidant capacity of herbs and spices after harvest, as well as testing their effects on markers of oxidation. This will work in parallel with clinical trials that are aiming to establish antioxidants as mediators of disease prevention. From a dietary perspective, the functionality of herbs and spices will be exposed through consideration of their properties as foods. As with most foods, the real benefits of including them in the diet are likely to emerge with a better understanding of the attributes of health that are best supported by food, and in methodological developments addressing the evidence base for their effects. These developments are well underway through evidence-based frameworks for substantiating health claims related to foods. At present, recommendations are warranted to support the consumption of foods rich in bioactive components, such as herbs and spices. With time, we can expect to see a greater body of scientific evidence supporting the benefits of herbs and spices in the overall maintenance of health and protection from disease.Linda C Tapsell, Ian Hemphill, Lynne Cobiac, David R Sullivan, Michael Fenech, Craig S Patch, Steven Roodenrys, Jennifer B Keogh, Peter M Clifton, Peter G Williams, Virginia A Fazio and Karen E Ing