Do Pomegranate Hydrolyzable Tannins and Their Derived Metabolites Provide Relief in Osteoarthritis? Findings from a Scoping Review.

Osteoarthritis (OA) is the most common form of arthritis affecting both the elderly and the middle-aged population. Although various therapeutics have been developed to arrest the structural deterioration of cartilage, the current treatments are limited to delay the progress of OA clinically. Therefore, it is pivotal to study new therapeutic agents for chondroprotection and the prevention of cartilage degeneration. Hydrolyzable tannin (HT)-containing foods aroused considerable interest in recent years for their relevant anti-inflammatory effects. The focus of this scoping review is to provide an overview of the evidence of the therapeutic potential of HTs and their metabolites in preventing or alleviating the course of OA. A broad search of PubMed and Scopus databases on this topic resulted in 156 articles. After the exclusion of reviews and not relevant records, 31 articles were retrieved. Although only some papers did not consider the biotransformation of HTs, most recent studies also have investigated the effect of HT metabolites. Further larger clinical trials, with an in-deep analysis of HT metabolization, are still needed to unravel the potential benefits of these compounds in OA, paving the way towards the development of a dietary strategy for the improvement of pro-inflammatory cytokine-induced chondrocyte dysfunctions and injuries.

(Poly)phenolic Content and Profile and Antioxidant Capacity of Whole-Grain Cookies are Better Estimated by Simulated Digestion than Chemical Extraction.

It is widely recognized that the biological effects of phytochemicals cannot be attributed to the native compounds present in foods but rather to their metabolites endogenously released after intake. Bioavailability depends on bioaccessibility, which is the amount of the food constituent that is released from the matrix in the gastrointestinal tract. The use of chemical extraction to evaluate the content and profile of phytochemicals does not mirror the physiological situation in vivo, and their bioaccessibility should be considered while assessing their nutritional significance in human health. The current study was designed to compare the (poly)phenolic profile and content and antioxidant capacity of whole-grain (WG) cookies using chemical extraction and a more physiological approach based on simulated digestion. Three types of organic WG cookies (made with durum, Italian khorasan, or KAMUT® khorasan wheat) were considered, either fermented by Saccharomyces Cerevisiae or sourdough. Although the flour type and the fermentation process influenced the release of phytochemicals from the cookie matrix, in almost all samples, the simulated digestion appeared the most efficient procedure. Our results indicate that the use of chemical extraction for evaluation of the phytochemicals content and antioxidant capacity of food could lead to underestimation and underline the need for more physiological extraction methods.

Resveratrol and inflammatory bowel disease: the evidence so far.

Despite the fact that inflammatory bowel disease (IBD) has still no recognised therapy, treatments which have proven at least mildly successful in improving IBD symptoms include anti-inflammatory drugs and monoclonal antibodies targeting pro-inflammatory cytokines. Resveratrol, a natural (poly)phenol found in grapes, red wine, grape juice and several species of berries, has been shown to prevent and ameliorate intestinal inflammation. Here, we discuss the role of resveratrol in the improvement of inflammatory disorders involving the intestinal mucosa. The present review covers three specific aspects of resveratrol in the framework of inflammation: (i) its content in food; (ii) its intestinal absorption and metabolism; and (iii) its anti-inflammatory effects in the intestinal mucosa in vitro and in the very few in vivo studies present to date. Actually, if several studies have shown that resveratrol may down-regulate mediators of intestinal immunity in rodent models, only two groups have performed intervention studies in human subjects using resveratrol as an agent to improve IBD conditions. The effects of resveratrol should be further investigated by conducting well-designed clinical trials, also taking into account different formulations for the delivery of the bioactive compound.

Dairy products and inflammation: A review of the clinical evidence.

Inflammation is a major biological process regulating the interaction between organisms and the environment, including the diet. Because of the increase in chronic inflammatory diseases, and in light of the immune-regulatory properties of breastfeeding, the ability of dairy products to modulate inflammatory processes in humans is an important but unresolved issue. Here, we report a systematic review of 52 clinical trials investigating inflammatory markers in relation to the consumption of dairy products. An inflammatory score (IS) was defined to quantitatively evaluate this interaction. The IS was significantly positive for the entire data set, indicating an anti-inflammatory activity in humans. When the subjects were stratified according to their health status, the IS was strongly indicative of an anti-inflammatory activity in subjects with metabolic disorders and of a pro-inflammatory activity in subjects allergic to bovine milk. Stratifying the data by product categories associated both low-fat and high-fat products, as well as fermented products, with an anti-inflammatory activity. Remarkably, the literature is characterized by a large gap in knowledge on bioavailability of bioactive nutrients. Future research should thus better combine food and nutritional sciences to adequately follow the fate of these nutrients along the gastrointestinal and metabolic axes.

Is cytotoxicity a determinant of the different in vitro and in vivo effects of bioactives?

BACKGROUND: Foodstuffs of both plant and animal origin contain a wide range of bioactive compounds. Although human intervention studies are mandatory to assess the health effects of bioactives, the in vitro approach is often used to select the most promising molecules to be studied in vivo. To avoid misleading results, concentration and chemical form, exposure time, and potential cytotoxicity of the tested bioactives should be carefully set prior to any other experiments. METHODS: In this study the possible cytotoxicity of different bioactives (docosahexaenoic acid, propionate, cyanidin-3-O-glucoside, protocatechuic acid), was investigated in HepG2 cells using different methods. Bioactives were supplemented to cells at different concentrations within the physiological range in human blood, alone or in combination, considering two different exposure times. RESULTS: Reported data clearly evidence that in vitro cytotoxicity is tightly related to the exposure time, and it varies among bioactives, which could exert a cytotoxic effect even at a concentration within the in vivo physiological blood concentration range. Furthermore, co-supplementation of different bioactives can increase the cytotoxic effect. CONCLUSIONS: Our results underline the importance of in vitro cytotoxicity screening that should be considered mandatory before performing studies aimed to evaluate the effect of bioactives on other cellular parameters. Although this study is far from the demonstration of a toxic effect of the tested bioactives when administered to humans, it represents a starting point for future research aimed at verifying the existence of a potential hazard due to the wide use of high doses of multiple bioactives.

Ancient wheat and health: a legend or the reality? A review on KAMUT khorasan wheat.

After WWII, the industrialized agriculture selected modern varieties of Triticum turgidum spp. durum and spp. aestivum (durum wheat and common wheat) based on higher yields and technological characteristics. Nowadays, the use of whole ancient grains and pseudo cereals is considered nutritionally important. How ancient grains have positive effects is not entirely known, the fragmentation of the scientific knowledge being also related to the fact that ancient grains are not a homogeneous category. The KAMUT® trademark indicates a specific and ancient variety of grain (Triticum turgidum ssp. turanicum, commonly khorasan wheat), and guarantees certain attributes making studies sufficiently comparable. In this work, studies on KAMUT® khorasan wheat have been systematically reviewed, evidencing different aspects supporting its benefits. Although it is not possible to establish whether all ancient grains share these positive characteristics, in total or in part, this review provides further evidences supporting the consumption of ancient grains.

Evidence of a DHA Signature in the Lipidome and Metabolome of Human Hepatocytes.

Cell supplementation with bioactive molecules often causes a perturbation in the whole intracellular environment. Omics techniques can be applied for the assessment of this perturbation. In this study, the overall effect of docosahexaenoic acid (DHA) supplementation on cultured human hepatocyte lipidome and metabolome has been investigated using nuclear magnetic resonance (NMR) in combination with traditional techniques. The effect of two additional bioactives sharing with DHA the lipid-lowering effect-propionic acid (PRO) and protocatechuic acid (PCA)-has also been evaluated in the context of possible synergism. NMR analysis of the cell lipid extracts showed that DHA supplementation, alone or in combination with PCA or PRO, strongly altered the cell lipid profile. The perfect discrimination between cells receiving DHA (alone or in combination) and the other cells reinforced the idea of a global rearrangement of the lipid environment induced by DHA. Notably, gas chromatography and fluorimetric analyses confirmed the strong discrimination obtained by NMR. The DHA signature was evidenced not only in the cell lipidome, but also in the metabolome. Results reported herein indicate that NMR, combined with other techniques, represents a fundamental approach to studying the effect of bioactive supplementation, particularly in the case of molecules with a broad spectrum of mechanisms of action.

The molecular mechanism of the cholesterol-lowering effect of dill and kale: The influence of the food matrix components.

Foods are complex matrices containing many different compounds, all of which contribute to the overall effect of the food itself, although they have different mechanisms of action. While evaluating the effect of bioactive compounds, it is important to consider that the use of a single compound can hide the effects of the other molecules that can act synergistically or antagonistically in the same food. The aim of the present study was to evaluate the influence of food matrix components by comparing two edible plants (dill and kale) with cholesterol-lowering potential and similar contents of their most representative bioactive, quercetin. The molecular effects of the extracts were evaluated in HepG2 cells by measuring the expression of sterol-regulatory element-binding proteins (SREBPs), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and low density lipoprotein receptor (LDLR) at the mRNA and protein level. The results reported here show that both extracts reduced the cellular cholesterol level with a similar trend and magnitude. It is conceivable that the slightly different results are due to the diverse composition of minor bioactive compounds, indicating that only by considering food as a whole is it possible to understand the complex relationship between food, nutrition, and health in a foodomics vision.

The foodomics approach for the evaluation of protein bioaccessibility in processed meat upon in vitro digestion.

The present work describes a foodomics protocol coupling an in vitro static simulation of digestion to a combination of omics techniques, to grant an overview of the protein digestibility of a meat-based food, namely Bresaola. The proteolytic activity mediated by the digestive enzymes is evaluated through Bradford and SDS-PAGE assays, combined to NMR relaxometry and spectroscopy, to obtain information ranging from the microscopic to the molecular level, respectively. The simple proteomics tool adopted here points out that a clear increase of bioaccessible proteins occurs in the gastric phase, rapidly disappearing during the following duodenal digestion. However, SDS-PAGE and the Bradford assay cannot follow the fate of the digested proteins when the products are sized <5 kDa. Conversely, NMR spectroscopy is able to capture the overall molecular profile of small fragments and peptides, which are mainly formed during the duodenal phase, thus giving the kinetics of the whole digestion process. Time domain NMR relaxometry, finally, detects the swelling phenomenon occurring during the gastric phase, when the digestion fluid enters the meat matrix.

Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells.

In recent years, the number of scientific papers concerning pomegranate (Punica granatum L.) and its health properties has increased greatly, and there is great potential for the use of bioactive-rich pomegranate extracts as ingredients in functional foods and nutraceuticals. To translate this potential into effective strategies it is essential to further elucidate the mechanisms of the reported bioactivity. In this study HepG2 cells were supplemented with a pomegranate fruit extract or with the corresponding amount of pure punicalagin, and then subjected to an exogenous oxidative stress. Overall, upon the oxidative stress the gene expression and activity of the main antioxidant enzymes appeared reduced in supplemented cells, which were more prone to the detrimental effects than unsupplemented ones. No differences were detected between cells supplemented with the pomegranate juice or the pure punicalagin. Although further studies are needed due to the gaps existing between in vitro and in vivo studies, our results suggest caution in the administration of high concentrations of nutraceutical molecules, particularly when they are administered in concentrated form.

Cholesterol-lowering probiotics: in vitro selection and in vivo testing of bifidobacteria.

Thirty-four strains of bifidobacteria belonging to Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, and Bifidobacterium pseu-docatenulatum were assayed in vitro for the ability to assimilate cholesterol and for bile salt hydrolase (BSH) against glycocholic and taurodeoxycholic acids (GCA and TDCA). Cholesterol assimilation was peculiar characteristic of two strains belonging to the species B. bifidum (B. bifidum MB 107 and B. bifidum MB 109), which removed 81 and 50 mg of cholesterol per gram of biomass, being the median of specific cholesterol absorption by bifidobacteria 19 mg/g. Significant differences in BSH activities were not established among bifidobacterial species. However, the screening resulted in the selection of promising strains able to efficiently deconjugate GCA and TDCA. No relationship was recognized between BSH phenotype and the extent of cholesterol assimilation. On the basis of cholesterol assimilation or BSHGCA and BSHTDCA activities, B. bifidum MB 109 (DSMZ 23731), B. breve MB 113 (DSMZ 23732), and B. animalis subsp. lactis MB 2409 (DSMZ 23733) were combined in a probiotic mixture to be fed to hypercholesterolemic rats. The administration of this probiotic formulation resulted in a significant reduction of total cholesterol and low-density cholesterol (LDL-C), whereas it did not affect high-density cholesterol (HDL-C) and HDL-C/LDL-C ratio.

Traditional foods for health: screening of the antioxidant capacity and phenolic content of selected Black Sea area local foods.

BACKGROUND: The nutritional characteristics of the Black Sea area (BSA) traditional foods are almost unknown, and they could be interesting sources of antioxidant compounds. In this study, carried out within the BaSeFood project, the in vitro total antioxidant capacity (TAC) and phenolic content of 39 BSA traditional foods were determined using different assays. RESULTS: An ample range of TAC and phenolics content was detected in the examined foods that were ranked according to their scavenging activity expressed per weight unit and per serving size. Based on serving size, the highest TAC was in the order blueberries > nettle soup > sunflower seeds, and the fruits/fruit-based foods group was the one having the highest activity. Correlation analysis evidenced that the TAC is highly dependent on total phenolic content, while hydroxycinnamic acids and compounds having o-diphenolic structure did not show specific prominent effects. Finally, correlations between the two methods used for measuring the TAC suggest that they are both suitable in a wide range of foods. CONCLUSION: Our data represent the first contribution to further research on the health effects of BSA traditional foods. This could enhance the interest of consumers, with potential benefits to stakeholders at all levels of the production chain.

Bioactive-rich Sideritis scardica tea (mountain tea) is as potent as Camellia sinensis tea at inducing cellular antioxidant defences and preventing oxidative stress.

BACKGROUND: In several countries, tea (hot-water infusions of dried Camellia sinensis (CS) leaves) is a major source of antioxidant flavonoids, and its consumption has been associated with several favourable outcomes. Other plants used for the preparation of herbal teas are sources of phenolic antioxidant compounds; among them Sideritis scardica (SS) is used for the preparation of a popular drink throughout Eastern and Central Europe. We have compared the effects of an SS extract to a CS extract in HepG2 cells to set the scientific basis for the exploitation of other herbal teas in counteraction of oxidative stress. RESULTS: Although SS extract had a lower phenolic concentration and total antioxidant capacity than CS extract, their cellular antioxidant effects were similar. The different phenolic pattern of the extracts suggests that the protective activity is not limited to catechins. CONCLUSION: Although further research is needed, our data represent a first contribution for the evaluation of the potential effect of SS in increasing antioxidant defences. © 2013 Society of Chemical Industry.

Phytosterol supplementation reduces metabolic activity and slows cell growth in cultured rat cardiomyocytes.

Besides being cholesterol-lowering agents, phytosterols (PS) can inhibit the growth and development of tumours. The anti-neoplastic activity is accounted for by PS incorporation into cell membranes, resulting in the interference of membrane functionality. The similarity between the PS cholesterol-lowering and anti-neoplastic effective doses deserves attention on the possible adverse effects even in non-neoplastic cells. To date, few studies have addressed the clarification of this important issue. In the present study, we supplemented primary, non-neoplastic neonatal rat cardiomyocytes with two different PS concentrations (3 or 6 µg/ml), both within the range of human plasma concentration. Cardiac cells were chosen as an experimental model since the heart has been reported as the target organ for subchronic toxicity of PS. Following supplementation, a dose-dependent incorporation of PS and a decrease in cholesterol content were clearly evidenced. PS did not induce apoptosis but caused a reduction in metabolic activity (measured as 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) conversion) and a slowing down of cell growth. The lower MTT conversion and the similar lactate dehydrogenase release could suggest that PS more efficiently target mitochondria than plasma membrane integrity. The replacement of cholesterol by PS could also have caused the observed slowing down of cell growth and the reduction in metabolic activity, which could rely on the PS increase, cholesterol decrease, or both. The present study is the first report on the effect of PS in cardiac cells, and although it is difficult to translate the obtained results to the health of heart tissue, it raises concerns about the safety of long-term exposure to physiologically relevant PS concentrations.

NMR comparison of in vitro digestion of Parmigiano Reggiano cheese aged 15 and 30 months.

The content of essential amino acids is an important aspect for determining the nutritional value of food proteins, but their digestibility is also a key property, deeply affected by food processing. The production of Parmigiano Reggiano cheese is closely related to the nutritional quality of the final product; in particular the high digestibility of its proteins is claimed to be proportional to cheese aging. Two different kinds of Parmigiano Reggiano, young (aged 15 months) and old (aged 30 months), were separately digested using an in vitro system that simulates digestive processes in the mouth, stomach and small intestine. Samples were collected at different stages of digestion and the process of protein hydrolysis was explored and compared by low-field (LF) and high-resolution (HR) NMR, together with other biochemical methods. HR-NMR allowed to simultaneously observe the quantity of free amino acids, peptides and proteins, also giving for these latter qualitative information about their dimension. LF-NMR, instead, gave the possibility to observe digestion with no treatments whatsoever, thus representing a technique suitable for on-line measurements. The results pointed out that cheeses with different aging times, although starting from distinct initial compositions, conclude digestion in a similar way, in terms of free amino acids and small organic compounds, but evolve with different kinetics of hydrolysis and peptide formation, discriminating the young from the old cheese.

Feasibility and effectiveness of Dialectical-Behavior Therapy for patients with borderline personality disorder in Italian mental health services: a preliminary study.

Dialectical-Behavior Therapy (DBT) is an evidence-based effective psychotherapeutic intervention for patients with Borderline Personality Disorder (BPD). There is a paucity of empirical evidences on the feasibility and the effectiveness of DBT in real-world Italian mental health services. This study aimed at reporting preliminary data on the implementation of DBT for adult patients with BPD attending an Italian mental health service. 28 BPD patients attending a mental health service underwent a 16-session DBT program. Effects of DBT were measured with the Difficulties in Emotion Regulation Scale (DERS) and the Barratt Impulsiveness Scale (BIS-11). 17 patients completed the DBT program, reporting reduced levels of emotion dysregulation and impulsiveness at follow up in comparison with baseline. Higher emotional dysregulation was a risk factor for dropout. In conclusion, this preliminary pilot study suggests that DBT is feasible and effective for BPD patients in Italian adult mental health services.

Pre-Pregnancy Diet and Vaginal Environment in Caucasian Pregnant Women: An Exploratory Study.

Vaginal microbes and their metabolic products have crucial functions, affecting local immunity development and maternal-fetal health. The composition of the vaginal microbiome can vary in response to various factors, including body mass index (BMI), and diet. In this study we get new insights into the vaginal ecosystem of Caucasian women (n = 24) at the first trimester of pregnancy, assessing whether pre-pregnancy diet can affect the structure of the vaginal environment in terms of bacterial composition and vaginal metabolite concentration. We characterized 1) the vaginal bacterial composition (Nugent score), 2) the vaginal metabolic profiles (1H-NMR spectroscopy), and 3) the dietary nutrient intake by means of a validated food frequency questionnaire. Pre-pregnancy BMI was negatively related to vaginal health status, indicating that women who begin pregnancy overweight/obese have a greater occurrence of vaginal dysbiosis during pregnancy. A lactobacilli-dominated vaginal microbiota was negatively associated with higher pre-pregnancy intake of animal-sourced protein. Conversely, a higher pre-pregnancy consumption of total carbohydrates and sugars seemed to be a protective factor for vaginal health. The vaginal environment of BV-women was characterized by higher levels of biogenic amines and organic acids, whereas higher levels of phenylpropionate and diverse amino acids were fingerprints of a healthy vaginal status. A significant association between a higher pre-pregnancy BMI and several dysbiosis-related vaginal metabolites was also found. Our study shed light on the role of pre-pregnancy BMI and diet on the vaginal environment during pregnancy, underlining the importance of limiting protein intake from animal foods to maintain a healthy lactobacilli-dominated microbiota.

Unveiling the Correlation between Inadequate Energy/Macronutrient Intake and Clinical Alterations in Volunteers at Risk of Metabolic Syndrome by a Predictive Model.

Although lifestyle-based interventions are the most effective to prevent metabolic syndrome (MetS), there is no definitive agreement on which nutritional approach is the best. The aim of the present retrospective analysis was to identify a multivariate model linking energy and macronutrient intake to the clinical features of MetS. Volunteers at risk of MetS (F = 77, M = 80) were recruited in four European centres and finally eligible for analysis. For each subject, the daily energy and nutrient intake was estimated using the EPIC questionnaire and a 24-h dietary recall, and it was compared with the dietary reference values. Then we built a predictive model for a set of clinical outcomes computing shifts from recommended intake thresholds. The use of the ridge regression, which optimises prediction performances while retaining information about the role of all the nutritional variables, allowed us to assess if a clinical outcome was manly dependent on a single nutritional variable, or if its prediction was characterised by more complex interactions between the variables. The model appeared suitable for shedding light on the complexity of nutritional variables, which effects could be not evident with univariate analysis and must be considered in the framework of the reciprocal influence of the other variables.

Food-derived bioactives as potential regulators of the IL-12/IL-23 pathway implicated in inflammatory bowel diseases.

The gene-specific modulation of inflammatory cytokines by food bioactives represents a possible approach to the nutritional or pharmaceutical prevention and treatment of inflammatory bowel disease (IBD). There is evidence for a key role of the interleukin-12beta1/23 receptor (IL-12 Rbeta1/23 R) pathway in IBD, and that reduction of the normal expression of the IL-23 R gene may provide a therapeutic target for this disease. The binding of interleukin-23 (IL-23) to its receptor IL-23 R regulates a newly defined effector T-cell subset, Th17 cells, characterised by the production of interleukin-17 (IL-17) and other cytokines, including tumour necrosis factor-alpha (TNF-alpha). In this study we developed an assay that measured IL-17 and TNF-alpha expression after incubation with specific dietary bioactives in the human T-cell Kit 225. It is anticipated that these changes will reflect differences in IL-23 R production, albeit indirectly. The cell line Kit 225 has similarities to Th17 cells, a subset of T cells producing IL-17 and TNF-alpha, and in initial experiments we demonstrated that the cells express both IL-23 receptor subunits, as well as IL-17 and TNF-alpha genes. Upon verification that stimulation of Kit 225 cells with 1ng/mL IL-23 significantly upregulated IL-17 and TNF-alpha gene expression, and IL-17 production, we supplemented cells with selected food bioactives, caffeic acid phenethyl ester (CAPE), epigallocatechin gallate (EGCG), docosahexaenoic acid (DHA), and linoleic acid (LA), and with phorbol myristate acetate (PMA) and sodium salicylate, used as pro-inflammatory and anti-inflammatory controls, respectively. In both unstimulated cells and after IL-23 stimulation, bioactives modulated the pro-inflammatory cytokines involved in IBD, underlining the possible role of foods in this disease. EGCG and DHA, which significantly inhibited both IL-17 and TNF-alpha expression, appeared particularly interesting.

Co-Administration of Propionate or Protocatechuic Acid Does Not Affect DHA-Specific Transcriptional Effects on Lipid Metabolism in Cultured Hepatic Cells.

Long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) are collectively recognized triglyceride-lowering agents, and their preventive action is likely mediated by changes in gene expression. However, as most studies employ fish oil, which contains a mixture of n-3 LC-PUFAs, the docosahexaenoic acid (DHA)-specific transcriptional effects on lipid metabolism are still unclear. The aim of the present study was to further elucidate the DHA-induced transcriptional effects on lipid metabolism in the liver, and to investigate the effects of co-administration with other bioactive compounds having effects on lipid metabolism. To this purpose, HepG2 cells were treated for 6 or 24 h with DHA, the short-chain fatty acid propionate (PRO), and protocatechuic acid (PCA), the main human metabolite of cyanidin-glucosides. Following supplementation, we mapped the global transcriptional changes. PRO and PCA alone had a very slight effect on the transcriptome; on the contrary, supplementation of DHA highly repressed the steroid and fatty acid biosynthesis pathways, this transcriptional modulation being not affected by co-supplementation. Our results confirm that DHA effect on lipid metabolism are mediated at least in part by modulation of the expression of specific genes. PRO and PCA could contribute to counteracting dyslipidemia through other mechanisms.