Cyclodextrins, Natural Compounds, and Plant Bioactives-A Nutritional Perspective

Cyclodextrins (CDs) are a group of cyclic oligosaccharides produced from starch or starch derivatives. They contain six (αCD), seven (βCD), eight (γCD), or more glucopyranose monomers linked via α-1,4-glycosidic bonds. CDs have a truncated cone shape with a hydrophilic outer wall and a less hydrophilic inner wall, the latter forming a more apolar internal cavity. Because of this special architecture, CDs are soluble in water and can simultaneously host lipophilic guest molecules. The major advantage of inclusion into CDs is increased aqueous solubility of such lipophilic substances. Accordingly, we present studies where the complexation of natural compounds such as propolis and dietary plant bioactives (e.g., tocotrienol, pentacyclic triterpenoids, curcumin) with γCD resulted in improved stability, bioavailability, and bioactivity in various laboratory model organisms and in humans. We also address safety aspects that may arise from increased bioavailability of plant extracts or natural compounds owing to CD complexation. When orally administered, α- and βCD-which are inert to intestinal digestion-are fermented by the human intestinal flora, while γCD is almost completely degraded to glucose units by α-amylase. Hence, recent reports indicate that empty γCD supplementation exhibits metabolic activity on its own, which may provide opportunities for new applications

Taurine Enhances Iron-Related Proteins and Reduces Lipid Peroxidation in Differentiated C2C12 Myotubes

Taurine is a nonproteinogenic amino sulfonic acid in mammals. Interestingly, skeletal muscle is unable to synthesize taurine endogenously, and the processing of muscular taurine changes throughout ageing and under specific pathophysiological conditions, such as muscular dystrophy. Ageing and disease are also associated with altered iron metabolism, especially when there is an excess of labile iron. The present study addresses the question of whether taurine connects cytoprotective effects and redox homeostasis in a previously unknown iron-dependent manner. Using cultured differentiated C2C12 myotubes, the impact of taurine on markers of lipid peroxidation, redox-sensitive enzymes and iron-related proteins was studied. Significant increases in the heme protein myoglobin and the iron storage protein ferritin were observed in response to taurine treatment. Taurine supplementation reduced lipid peroxidation and BODIPY oxidation by ~60 and 25%, respectively. Furthermore, the mRNA levels of redox-sensitive heme oxygenase (Hmox1), catalase (Cat) and glutamate-cysteine ligase (Gclc) and the total cellular glutathione content were lower in taurine-supplemented cells than they were in the control cells. We suggest that taurine may inhibit the initiation and propagation of lipid peroxidation by lowering basal levels of cellular stress, perhaps through reduction of the cellular labile iron pool

Phenotyping of Drosophila Melanogaster-A Nutritional Perspective

The model organism Drosophila melanogaster was increasingly applied in nutrition research in recent years. A range of methods are available for the phenotyping of D. melanogaster, which are outlined in the first part of this review. The methods include determinations of body weight, body composition, food intake, lifespan, locomotor activity, reproductive capacity and stress tolerance. In the second part, the practical application of the phenotyping of flies is demonstrated via a discussion of obese phenotypes in response to high-sugar diet (HSD) and high-fat diet (HFD) feeding. HSD feeding and HFD feeding are dietary interventions that lead to an increase in fat storage and affect carbohydrate-insulin homeostasis, lifespan, locomotor activity, reproductive capacity and stress tolerance. Furthermore, studies regarding the impacts of HSD and HFD on the transcriptome and metabolome of D. melanogaster are important for relating phenotypic changes to underlying molecular mechanisms. Overall, D. melanogaster was demonstrated to be a valuable model organism with which to examine the pathogeneses and underlying molecular mechanisms of common chronic metabolic diseases in a nutritional context

Lithium Content of 160 Beverages and Its Impact on Lithium Status in Drosophila melanogaster

Lithium (Li) is an important micronutrient in human nutrition, although its exact molecular function as a potential essential trace element has not yet been fully elucidated. It has been previously shown that several mineral waters are rich and highly bioavailable sources of Li for human consumption. Nevertheless, little is known about the extent in which other beverages contribute to the dietary Li supply. To this end, the Li content of 160 different beverages comprising wine and beer, soft and energy drinks and tea and coffee infusions was analysed by inductively coupled plasma mass spectrometry (ICP-MS). Furthermore, a feeding study in Drosophila melanogaster was conducted to test whether Li derived from selected beverages changes Li status in flies. In comparison to the average Li concentration in mineral waters (108 µg/L; reference value), the Li concentration in wine (11.6 ± 1.97 µg/L) and beer (8.5 ± 0.77 µg/L), soft and energy drinks (10.2 ± 2.95 µg/L), tea (2.8 ± 0.65 µg/L) and coffee (0.1 ± 0.02 µg/L) infusions was considerably lower. Only Li-rich mineral water (~1600 µg/L) significantly increased Li concentrations in male and female flies. Unlike mineral water, most wine and beer, soft and energy drink and tea and coffee samples were rather Li-poor food items and thus may only contribute to a moderate extent to the dietary Li supply. A novelty of this study is that it relates analytical Li concentrations in beverages to Li whole body retention in Drosophila melanogaster

Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males

<p>Abstract</p> <p>Background</p> <p>Human paraoxonase 1 (PON1) is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary heart diseases and underlying atherogenesis. The common <it>PON1 </it>Q192R polymorphism (<it>rs662</it>, A>G), a glutamine to arginine substitution at amino acid residue 192, has been analyzed in numerous association studies as a genetic marker for coronary heart diseases, however, with controversial results.</p> <p>Findings</p> <p>To get a better understanding about the pathophysiological function of PON1, we analyzed the relationships between the Q192R polymorphism, serum paraoxonase activity and serum biomarkers important for atherogenesis. Genotyping a cohort of 49 healthy German males for the Q192R polymorphism revealed an allele distribution of 0.74 and 0.26 for the Q and R allele, respectively, typical for Caucasian populations. Presence of the R192 allele was found to be associated with a significantly increased paraoxonase enzyme activity of 187.8 ± 11.4 U/l in comparison to the QQ192 genotype with 60.5 ± 4.9 U/l. No significant differences among the genotypes were found for blood pressure, asymmetric dimethylarginine, LDL, HDL, triglycerides, and cholesterol. As expected, MIP-2 alpha a cytokine rather not related to atherosclerosis is not affected by the <it>PON1 </it>polymorphism. In contrast to that, the pro-inflammatory cytokine TNF-alpha is enhanced in R192 carriers (163.8 ± 24.7 pg/ml vs 94.7 ± 3.2 pg/ml in QQ192 carriers).</p> <p>Conclusions</p> <p>Our findings support the hypothesis that the common <it>PON1 </it>R192 allele may be a genetic risk factor for atherogenesis by inducing chronic low-grade inflammation.</p

High Dietary Kuding Tea Extract Supplementation Induces Hepatic Xenobiotic-Metabolizing Enzymes-A 6-Week Feeding Study in Mice

Kuding tea (KT) is a traditional Chinese beverage rich in plant bioactives that may exhibit various health benefits. However, little is known about the safety of KT extract (KTE) when consumed long term at high doses as a dietary supplement. Therefore, in this study, we investigated aspects of the safety of KTE. Male C57BL/6 mice were fed a high-fat, high-fructose, Western-type diet (control) supplemented with either 12.88% γ-cyclodextrin (γCD), 7.12% KTE (comprising 0.15% ursolic acid, UA) encapsulated in 12.88% γCD (KTE-γCD), or 0.15% UA over a 6-week experimental period. The dietary treatments did not affect food intake, body weight or body composition. However, treatment with KTE-γCD, but not γCD and UA, increased liver weight and hepatic fat accumulation, which was accompanied by increased hepatic PPARγ and CD36 mRNA levels. KTE-γCD treatment elevated plasma cholesterol and CYP7A1 mRNA and protein levels compared to those in control mice. KTE-γCD substantially increased the mRNA and protein levels of hepatic CYP3A and GSTA1, which are central to the detoxification of drugs and xenobiotics. Furthermore, we observed a moderate elevation in hepatic CYP3A (5-fold change) and GSTA1 (1.7-fold change) mRNA levels in UA-fed mice. In vitro data collected in HepG2 cells indicated a dose-dependent increase in hepatic cytotoxicity in response to KTE treatment, which may have been partly mediated by UA. Overall, the present data may contribute to the safety assessment of KTE and suggest that KTE encapsulated in γCD affects liver fat storage and the hepatic phase I and phase II responses in mice

Avens Root (Geum Urbanum L.) Extract Discovered by Target-Based Screening Exhibits Antidiabetic Activity in the Hen's Egg Test Model and Drosophila melanogaster

Medicinal plant extracts are becoming increasingly important as an alternative for traditional drugs against diabetes mellitus (DM). For this reason, we initialized a target-based screening of 111 root extracts from an open access plant extract library (PECKISH) by ascertaining their in-vitro inhibitory efficacy on α-glucosidase. The two most active extracts Geum urbanum L. (roseroot) and Rhodiola rosea L. (avens root) were further tested for their antidiabetic activities in terms of their impact on different regulatory key points of glucose homeostasis. To this end, various enzyme- and cell culture-based in-vitro assays were employed including the determination of sodium-dependent glucose transporter 1 (SGLT1) activity in Caco-2 monolayers by Ussing chambers and of glucose transporter 4 (GLUT4) translocation in a GFP-reporter cell line. Subsequently, the antidiabetic potential of the root extracts were further evaluated in in-vivo models, namely hen's eggs test and the fruit fly Drosophila melanogaster. Avens root extract was found to be a more potent inhibitor of the enzymes α-glucosidase and dipeptidyl peptidase-4 (DPP4) than roseroot extract. Most importantly, only avens root extract exhibited antidiabetic activity in the two in-vivo models eliciting a reduced blood glucose level in the in-ovo model and a decline of the triglyceride level in a dietary starch-induced D. melanogaster obesity model. Analyses of the polyphenolic composition of the avens root extract by HPLC revealed a high content of ellagic acid and its derivatives as well as ellagitannins such as pedunculagin, stenophyllanin, stachyurin, casuarinin and gemin A. In conclusion, avens root extract represents a promising medicinal plant that should be considered in further in-vivo studies on hyperglycemia in laboratory rodents and humans

Dietary lithium intake, graft failure and mortality in kidney transplant recipients

BACKGROUND &amp; AIMS: Long-term high dose lithium therapy in bipolar disorder is known to adversely affect kidney function. However, recent animal studies revealed that low amounts of lithium are beneficial for the kidney when it is damaged by exposure to nephrotoxic compounds, inflammation, or oxidative stress. This study aimed to investigate whether urinary lithium excretion, reflecting dietary lithium intake, is associated with adverse long-term kidney graft outcomes and patient survival.METHODS: Urinary lithium concentration was measured using inductively coupled plasma-mass-spectrometry in 642 stable kidney transplant recipients. Graft failure was defined as start of dialysis or re-transplantation, and kidney function decline was defined as doubling of serum creatinine.RESULTS: Median [interquartile range] urinary lithium excretion was 3.03 [2.31-4.01] μmol/24 h. Urinary lithium excretion was associated with energy, plant protein and water intake. During a median follow-up of 5.3 [4.5-6.0] years, 79 (12%) KTR developed graft failure and 127 (20%) KTR developed kidney function decline. Higher urinary lithium excretion was associated with lower risk of graft failure (hazard ratio [95% confidence interval]: 0.54 [0.38-0.79] per log2 μmol/24 h) and kidney function decline (HR [95% CI]: 0.73 [0.54-0.99] per log2 μmol/24 h). These associations remained independent of adjustment for potential confounders and in sensitivity analyses. There was significant effect modification by use of proliferation inhibitors (P = 0.05) and baseline eGFR (P &lt; 0.001), with higher urinary lithium excretion being more protective in KTR not using proliferation inhibitors and in KTR with lower baseline eGFR. Furthermore, higher urinary lithium excretion was associated with reduced risk of all-cause mortality (HR [95% CI]: 0.64 [0.49-0.83]; P = 0.001).CONCLUSION: Dietary lithium intake may be a potentially modifiable-yet rather overlooked-risk factor for adverse long-term kidney graft outcomes and patient survival.</p

Dietary lithium intake, graft failure and mortality in kidney transplant recipients

BACKGROUND &amp; AIMS: Long-term high dose lithium therapy in bipolar disorder is known to adversely affect kidney function. However, recent animal studies revealed that low amounts of lithium are beneficial for the kidney when it is damaged by exposure to nephrotoxic compounds, inflammation, or oxidative stress. This study aimed to investigate whether urinary lithium excretion, reflecting dietary lithium intake, is associated with adverse long-term kidney graft outcomes and patient survival.METHODS: Urinary lithium concentration was measured using inductively coupled plasma-mass-spectrometry in 642 stable kidney transplant recipients. Graft failure was defined as start of dialysis or re-transplantation, and kidney function decline was defined as doubling of serum creatinine.RESULTS: Median [interquartile range] urinary lithium excretion was 3.03 [2.31-4.01] μmol/24 h. Urinary lithium excretion was associated with energy, plant protein and water intake. During a median follow-up of 5.3 [4.5-6.0] years, 79 (12%) KTR developed graft failure and 127 (20%) KTR developed kidney function decline. Higher urinary lithium excretion was associated with lower risk of graft failure (hazard ratio [95% confidence interval]: 0.54 [0.38-0.79] per log2 μmol/24 h) and kidney function decline (HR [95% CI]: 0.73 [0.54-0.99] per log2 μmol/24 h). These associations remained independent of adjustment for potential confounders and in sensitivity analyses. There was significant effect modification by use of proliferation inhibitors (P = 0.05) and baseline eGFR (P &lt; 0.001), with higher urinary lithium excretion being more protective in KTR not using proliferation inhibitors and in KTR with lower baseline eGFR. Furthermore, higher urinary lithium excretion was associated with reduced risk of all-cause mortality (HR [95% CI]: 0.64 [0.49-0.83]; P = 0.001).CONCLUSION: Dietary lithium intake may be a potentially modifiable-yet rather overlooked-risk factor for adverse long-term kidney graft outcomes and patient survival.</p