Trichinellosis is a re-emerging worldwide foodborne zoonosis. Oxidative stress is one of the most common detrimental effects caused by trichinellosis. In addition, Trichinella infection poses an infinite and major challenge to the host’s immune system. Resistance and side effects limit the efficiency of the existing anti-trichinella medication. Given that concern, this work aimed to investigate the anti-helminthic, antioxidant, anti-inflammatory and immunomodulatory effects of resveratrol and zinc during both phases of Trichinella spiralis infection. Sixty-four Swiss albino mice were divided into four equal groups: non-infected control, infected control, infected and treated with resveratrol, and infected and treated with zinc. Animals were sacrificed on the 7th and 35th days post-infection for intestinal and muscular phase assessments. Drug efficacy was assessed by biochemical, parasitological, histopathological, immunological, and immunohistochemical assays. Resveratrol and zinc can be promising antiparasitic, antioxidant, anti-inflammatory, and immunomodulatory agents, as evidenced by the significant decrease in parasite burden, the significant improvement of liver and kidney function parameters, the increase in total antioxidant capacity (TAC), the reduction of malondialdehyde (MDA) level, the increase in nuclear factor (erythroid-derived 2)-like-2 factor expression, and the improvement in histopathological findings. Moreover, both drugs enhanced the immune system and restored the disturbed immune balance by increasing the interleukin 12 (IL-12) level. In conclusion, resveratrol and zinc provide protection for the host against oxidative harm and the detrimental effects produced by the host’s defense response during Trichinella spiralis infection, making them promising natural alternatives for the treatment of trichinellosis.

Aging is the most prominent risk factor for many diseases, which is considered to be a complicated biological process. The rate of aging depends on the effectiveness of important mechanisms such as the protection of DNA from free radicals, which protects the structural and functional integrity of cells and tissues. In any organism, not all organs may age at the same rate. Slowing down primary aging and reaching maximum lifespan is the most basic necessity. In this process, it may be possible to slow down or stabilise some diseases by using the compounds for both dietary and pharmacological purposes. Natural compounds with antioxidant and anti-inflammatory effects, mostly plant-based nutraceuticals, are preferred in the treatment of age-related chronic diseases and can also be used for other diseases. An increasing number of long-term studies on synthetic and natural compounds aim to elucidate preclinically and clinically the mechanisms underlying being healthy and prolongation of life. To delay age-related diseases and prolong the lifespan, it is necessary to take these compounds with diet or pharmaceuticals, along with detailed toxicological results. In this review, the most promising and utilised compounds will be highlighted and it will be discussed whether they have toxic effects in short/long-term use, although they are thought to be used safely.

Resveratrol supplementation during pregnancy and lactation has been associated with a reduced risk of maternal obesity, gestational diabetes mellitus , and preeclampsia. In addition, emerging evidence has shown that maternal resveratrol supplementation diminishes cardio-metabolic disorders in offspring, highlighting its role in modulating adaptative responses involving phenotypical plasticity. Therefore, it is reasonable to infer that administration of resveratrol during pregnancy and lactation periods could be considered an important nutritional intervention to decrease the risk of maternal and offspring cardio-metabolic disorders. To highlight these new insights, this literature review will summarize the understanding emerging from experimental and clinical studies about resveratrol supplementation and its capacity to prevent or minimize maternal and offspring cardio-metabolic disorders.

Olive oil and wine are consumed daily worldwide, and they constitute the fundamental pillars of the healthy Mediterranean diet. Polyphenolic compounds, naturally present in both olive oil and wine, are responsible for their beneficial properties. Current studies have shown the neuroprotective effects of polyphenols independently of their well-known antioxidant action. In this work, we have focused on reviewing the protective effect of polyphenols from extra virgin olive oil and wine in Alzheimer´s disease (AD), to emphasise that both foods could be a possible therapeutic tool. Beneficial effects have been described in β-aggregation, neurofibrillary tangles, autophagy and mitochondrial function, as well as in cerebral insulin resistance. Furthermore, to date, a harmful dose has not been described. Both pre-clinical and clinical works demonstrate that polyphenols act on neuropathological and cognitive disorders of AD, preventing or stopping the onset of this devastating disease. However, there are certain limitations in these studies, since it is very difficult to research diseases that lead to cognitive impairment. Although all the findings obtained are very encouraging, more studies should be carried out investigating the use of the polyphenols from olive oil and wine as therapeutic agents in the progression of AD. Therefore, more longitudinal studies in humans with a homogeneous cohort of patients are necessary to corroborate the efficacy of these nutraceuticals, as well as determine the most appropriate dose for this purpose.

Intake of resveratrol has been associated with improved ovarian morphology under in vitro and in the animal models; however, this finding has not been confirmed in trials. The aim of our study was, therefore, to use a placebo-controlled approach with the detailed assessment of the ovarian morphology by applying transvaginal ultrasound to examine the effectiveness of this therapeutic approach in this group of women. The mean age of all participants was 28·61 (sd 4·99) years, with the mean BMI of 28·26 (sd 5·62) kg/m2. Resveratrol therapy, as compared with placebo, was associated with a significantly higher rate of improvement in the ovarian morphology (P = 0·02). Women who received resveratrol had a more dominant follicle than those getting placebo, with a significant reduction in the ovarian volume (P < 0·05). However, the number of follicle count per ovary (FNPO), stromal area (SA), ovarian echogenicity and distribution of follicles were not significantly altered (P > 0·05). Forty-one women with polycystic ovary syndrome (PCOS) were randomly assigned (1:1) to 3 months of daily 1000 mg resveratrol or placebo. Random assignment was done by blocked randomisation. Our primary endpoints were the change in the ovarian volume, SA and antral FNPO from the baseline to 3 months. Secondary endpoints were improvement in the distribution of follicles and ovarian echogenicity. Differences between the resveratrol and control groups were evaluated by Chi-square, Fisher’s exact test and repeated-measures ANOVA. Treatment with resveratrol significantly reduced the ovarian volume and polycystic ovarian morphology, thus suggesting a disease-modifying effect in PCOS.

Excessive hepatic glycogen accumulation commonly impairs hepatocytes function and further produces negative effects on growth and health status of carnivorous fish. A 9-week feeding trial was conducted to explore the potential regulation of resveratrol (RSV) on high-carbohydrate-induced glycogen deposition and immune response of largemouth bass. Results showed that high dietary carbohydrate (10 % inclusion of starch) led to hepatic glycogen accumulation and post-prandial hyperglycemia compared with the diet with 5 % starch, which was both alleviated with the inclusion of RSV. The use of RSV promoted the expression of sirtuin 1, which was down-regulated by high dietary carbohydrate. Meanwhile, RSV inclusion promoted the expression of genes involved in insulin pathway and glycolysis and inhibited the expression of gluconeogenesis-related genes. Additionally, high dietary carbohydrate significantly reduced lysozyme content but increased complement C4 content, which were both reversed with RSV supplementation. Meanwhile, RSV inclusion inhibited the expression of pro-inflammatory cytokines but promoted anti-inflammatory cytokines expression, compared with the high carbohydrate treatment. In conclusion, RSV inclusion was beneficial in alleviating high-dietary-carbohydrate-induced glycogen accumulation and immune response in largemouth bass.

Probiotics and plant extracts are considered to prevent the development of non-alcoholic fatty liver disease (NAFLD). The present study explores the effects of using both probiotics and plant extracts on NAFLD. The present study evaluated the effects of plant extracts on lipid droplet accumulation and the growth of probiotics in vitro. A C57BL/6 mouse model was used to examine the effects of probiotics and plant extracts on NAFLD. Body weight and food intake were measured. The levels of serum lipids, oxidative stress and the liver injury index were determined using commercial kits. Haematoxylin and eosin staining, GC and real-time PCR were also used for analysis. The results revealed that administration of Lactobacillus casei YRL577 and L. paracasei X11 with resveratrol (RES) or tea polyphenols (TP) significantly reduced the levels of total cholesterol, TAG and LDL-cholesterol and increased the level of the HDL-cholesterol. The groups of L. casei YRL577 with RES and TP also regulated the liver structure, oxidative stress and injury. Furthermore, L. casei YRL577 with TP exhibited a more positive effect towards improving the NAFLD and increased the concentrations of the butyric acid than other three combined groups. L. casei YRL577 with TP up-regulated the mRNA levels of the farnesoid X receptor and fibroblast growth factor 15 and decreased the mRNA levels of the apical Na-dependent bile acid transporter. These findings showed that L. casei YRL577 + TP-modified genes in the intestinal bile acid pathway improved markers of NAFLD.

The objective of the present study was to elucidate whether resveratrol could facilitate the survival of boar sperm during liquid preservation and fast cooling processes. Boar semen were diluted with Modena extender containing different concentrations of resveratrol. Sperm motility was evaluated by visual estimation. Membrane integrity, acrosome integrity and mitochondrial membrane potentials were measured by SYBR-14/PI, FITC-PNA and JC-1 staining, respectively. Moreover, the levels of reactive oxygen species (ROS), malonaldehyde (MDA) and total antioxidant capacity (T-AOC) were measured using commercial assay kits. B-cell lymphoma protein-2 (BCL2) content was determined by western blotting. During liquid preservation at 17oC, the addition of 50 μM resveratrol to the Modena extender significantly improved sperm motility, membrane integrity, acrosome integrity, and sperm mitochondrial membrane potentials. Similar results were also observed in the 150 μM resveratrol group during the fast cooling process. Furthermore, addition of resveratrol led to a decrease of ROS and MDA, and an increase in the content of T-AOC and BCL2. These observations suggest that addition of resveratrol to Modena extender protects boar sperm against oxidative stress. The optimal concentrations of resveratrol are 50 μM and 150 μM during liquid preservation and fast cooling process, respectively.

Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements.

Trichinellosis is a serious food-borne zoonotic infection of cosmopolitan distribution. Currently, treatment for trichinellosis is far from ideal. Given the important role of oxidative stress and immune-mediated inflammation in the pathogenesis of trichinellosis, this study was designed to evaluate the possible protective effects of resveratrol (RSV) during the intestinal and muscular phases of Trichinella spiralis infection in mice. The oral administration of RSV at a dose of 20 mg/kg once daily for two weeks resulted in significant reductions in both adult and larval counts; significant improvements in the redox status of the small intestine and muscles; a significant reduction in interleukin 4, pentraxin 3 and vascular endothelial growth factor expression; and the mitigation of intestinal and muscular inflammation. In conclusion, this study identifies RSV as a promising agent for the treatment of experimental trichinellosis, and more studies in experimental animals and humans are worth consideration.

n-3 Fatty acids, flavonoids and resveratrol are well publicised for their beneficial effects on human health and wellbeing. Identifying common, underlying biological mechanisms targeted by these functional foods would therefore be informative for the public health sector for advising on nutritional health and disease, food and drug product development and consumer interest. The aim of this study was to explore the potential effects of gene expression changes associated with n-3 fatty acids EPA and DHA, flavonoids and resveratrol on modifying biological systems and disease pathways. To test this, publicly available human microarray data for significant gene expression changes associated with dietary intervention with EPA/DHA, flavonoids and resveratrol was subjected to pathway analysis and significance testing for overlap with signals from genome-wide association studies (GWAS) for common non-communicable diseases and biological functions. There was an enrichment of genes implicated in immune responses and disease pathways which was common to all of the treatment conditions tested. Analysis of biological functions and disease pathways indicated anti-tumorigenic properties for EPA/DHA. In line with this, significance testing of the intersection of genes associated with these functional foods and GWAS hits for common biological functions (ageing and cognition) and non-communicable diseases (breast cancer, CVD, diabesity, neurodegeneration and psychiatric disorders) identified significant overlap between the EPA/DHA and breast cancer gene sets. Dietary intervention with EPA/DHA, flavonoids and resveratrol can target important biological and disease pathways suggesting a potentially important role for these bioactive compounds in the prevention and treatment of dietary-related diseases.

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.

We produced a new chemical compound based on methylxanthines and polyphenols (CCMP) present in the chemical matrix of guaraná (Paullinia cupana), a seed extract with antioxidant properties. After supplementation with the standard extract of resveratrol, a well documented antioxidant found in other plant sources, we investigated whether this resveratrol-enriched compound could improve sperm viability and modulate differentially reactive oxygen species (ROS) and nitric oxide (NO) levels in thawed sperm. Sperm samples obtained from healthy young donors were treated with different concentrations of guaraná extract (0.1, 1, 5 or 10 mg/ml) and cells were frozen at −80°C for 24 h. In addition, the potential protective effects of guaraná treatment on sperm treated with pro-oxidant compound (200 µM hydrogen peroxide, H2O2) were assessed. Samples were also exposed to three concentrations of CCMP before being frozen in liquid nitrogen (−196°C) or in an ultrafreezer (−80°C) for 24 h, and both pre-freezing and post-thaw measurements of viability and oxidative stress were performed. Guaraná supplementation at 10 mg/ml significantly increased post-thaw viability and decreased oxidative metabolism of the sperm. Moreover, selected concentrations of CCMP improved viability and oxidative metabolism in sperm samples pre-freezing. Furthermore, CCMP showed cryoprotective activity by increasing viability and decreasing oxidative stress in post-thaw samples. In summary, these findings suggested that CCMP supplementation acts as a cryoprotectant to modulate ROS and NO levels in thawed sperm. CCMP could be used to enhance sperm quality and reproductive success.

In vitro studies have shown several beneficial properties of resveratrol. Epidemiological evidence is still scarce, probably because of the difficulty in estimating resveratrol exposure accurately. The current study aimed to assess the relationships between acute and habitual dietary resveratrol and wine intake and urinary resveratrol excretion in a European population. A stratified random subsample of 475 men and women from four countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study, who had provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day, were included. Acute and habitual dietary data were collected using standardised 24-HDR software and a validated country-specific dietary questionnaire, respectively. Phenol-Explorer was used to estimate the intake of resveratrol and other stilbenes. Urinary resveratrol was analysed using tandem MS. Spearman’s correlation coefficients between estimated dietary intakes of resveratrol and other stilbenes and consumption of wine, their main food source, were very high (r>0·9) when measured using dietary questionnaires and were slightly lower with 24-HDR (r>0·8). Partial Spearman’s correlations between urinary resveratrol excretion and intake of resveratrol, total stilbenes or wine were found to be higher when using the 24-HDR (R2partial approximately 0·6) than when using the dietary questionnaires (R2partial approximately 0·5). Moderate to high correlations between dietary resveratrol, total stilbenes and wine, and urinary resveratrol concentrations were observed. These support the earlier findings that 24-h urinary resveratrol is an effective biomarker of both resveratrol and wine intakes. These correlations also support the validity of the estimation of resveratrol intake using the dietary questionnaire and Phenol-Explorer.

Xanthohumol (Xan) is a natural constituent of human nutrition. Little is known about its actions on leishmanial parasites and their mitochondria as putative target. Therefore, we determined the antileishmanial activity of Xan and resveratrol (Res, as alternative compound with antileishmanial activity) with respect to mitochondria in Leishmania amazonensis promastigotes/amastigotes (LaP/LaA) in comparison with their activity in peritoneal macrophages from mouse (PMM) and macrophage cell line J774A.1 (J774). Mechanistic studies were conducted in Leishmania tarentolae promastigotes (LtP) and mitochondrial fractions isolated from LtP. Xan and Res demonstrated antileishmanial activity in LaA [half inhibitory concentration (IC50): Xan 7 µm, Res 14 µm]; while they had less influence on the viability of PMM (IC50: Xan 70 µm, Res >438 µm). In contrast to Res, Xan strongly inhibited oxygen consumption in Leishmania (LtP) but not in J774 cells. This was based on the inhibition of the mitochondrial electron transfer complex II/III by Xan, which was less pronounced with Res. Neither Xan nor Res increased mitochondrial superoxide release in LtP, while both decreased the mitochondrial membrane potential in LtP. Bioenergetic studies showed that LtP mitochondria have no spare respiratory capacity in contrast to mitochondria in J774 cells and can therefore much less adapt to stress by mitochondrial inhibitors, such as Xan. These data show that Xan may have antileishmanial activity, which is mediated by mitochondrial inhibition.

Decrease in muscle mass and performance with ageing is one of the main factors of frailty in the elderly. Maintenance of muscle performance by involving in physical activities is essential to increase independence and quality of life among elderly. The use of natural compounds with ergogenic activity in old people would increase the effect of moderate exercises in the maintenance of physiological muscle capacity. Resveratrol (RSV), a polyphenol found in walnuts, berries and grapes, shows this ergogenic activity. By using young, mature and old mice as models, we have found that RSV improves muscle performance in mature and old animals but not in young animals. Without showing significant effect by itself, RSV primed the effect of exercise by increasing endurance, coordination and strength in old animals. This effect was accompanied by a higher protection against oxidative damage and an increase in mitochondrial mass. RSV increased catalase and superoxide dismutase protein levels in muscle and primed exercise to reverse the decrease in their activities during ageing. Furthermore, RSV increased the level of mitochondrial mass markers such as cytochrome C, mitochondrial transcription factor A and nuclear respiratory factor-1 in muscle in exercised animals. Our results indicate that RSV can be considered an ergogenic compound that helps maintain muscle performance during ageing and subsequently reduces frailty and increases muscle performance in old individuals practising moderate exercise.

Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia. The aim of this study was to determine whether resveratrol, a polyphenol antioxidant compound, when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older, obese, diabetic rats. Diabetes was induced in 6-month old, obese, male Wistar rats via a single intravenous dose of streptozotocin (65 mg/kg). Randomly selected animals were administered resveratrol (2 mg/kg) via oral gavage daily for 8 weeks. Body weights, blood glucose levels, food intake and water consumption were monitored, and assessments of vascular reactivity, tactile allodynia and left ventricular function were performed. Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats (P<0·05). There were no significant changes in standardised vasorelaxation responses, plasma glucose concentrations, water consumption, body weight, left ventricular hypertrophy, kidney hypertrophy, heart rate or left ventricular compliance with resveratrol administration. Resveratrol-mediated improvements in vascular and nerve function in old, obese, diabetic rats were associated with its reported antioxidant effects. Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus (i.e. hyperglycaemia, polydypsia and a failure to thrive). This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus.

Diets rich in fruits and vegetables (FV), which contain (poly)phenols, protect against age-related inflammation and chronic diseases. T-lymphocytes contribute to systemic cytokine production and are modulated by FV intake. Little is known about the relative potency of different (poly)phenols in modulating cytokine release by lymphocytes. We compared thirty-one (poly)phenols and six (poly)phenol mixtures for effects on pro-inflammatory cytokine release by Jurkat T-lymphocytes. Test compounds were incubated with Jurkat cells for 48 h at 1 and 30 µm, with or without phorbol ester treatment at 24 h to induce cytokine release. Three test compounds that reduced cytokine release were further incubated with primary lymphocytes at 0·2 and 1 µm for 24 h, with lipopolysaccharide added at 5 h. Cytokine release was measured, and generation of H2O2 by test compounds was determined to assess any potential correlations with cytokine release. A number of (poly)phenols significantly altered cytokine release from Jurkat cells (P<0·05), but H2O2 generation did not correlate with cytokine release. Resveratrol, isorhamnetin, curcumin, vanillic acid and specific (poly)phenol mixtures reduced pro-inflammatory cytokine release from T-lymphocytes, and there was evidence for interaction between (poly)phenols to further modulate cytokine release. The release of interferon-γ induced protein 10 by primary lymphocytes was significantly reduced following treatment with 1 µm isorhamnetin (P<0·05). These results suggest that (poly)phenols derived from onions, turmeric, red grapes, green tea and açai berries may help reduce the release of pro-inflammatory mediators in people at risk of chronic inflammation.

Gestational diabetes mellitus (GDM) is a serious problem growing worldwide that needs to be addressed with urgency in consideration of the resulting severe complications for both mother and fetus. Growing evidence indicates that a healthy diet rich in fruit, vegetables, nuts, extra-virgin olive oil and fish has beneficial effects in both the prevention and management of several human diseases and metabolic disorders. In this review, we discuss the latest data concerning the effects of dietary bioactive compounds such as polyphenols and PUFA on the molecular mechanisms regulating glucose homoeostasis. Several studies, mostly based on in vitro and animal models, indicate that dietary polyphenols, mainly flavonoids, positively modulate the insulin signalling pathway by attenuating hyperglycaemia and insulin resistance, reducing inflammatory adipokines, and modifying microRNA (miRNA) profiles. Very few data about the influence of dietary exposure on GDM outcomes are available, although this approach deserves careful consideration. Further investigation, which includes exploring the ‘omics’ world, is needed to better understand the complex interaction between dietary compounds and GDM.

Energy restriction (ER; also known as caloric restriction) is the only nutritional intervention that has repeatedly been shown to increase lifespan in model organisms and may delay ageing in humans. In the present review we discuss current scientific literature on ER and its molecular, metabolic and hormonal effects. Moreover, criteria for the classification of substances that might induce positive ER-like changes without having to reduce energy intake are summarised. Additionally, the putative ER mimetics (ERM) 2-deoxy-d-glucose, metformin, rapamycin, resveratrol, spermidine and lipoic acid and their suggested molecular targets are discussed. While there are reports on these ERM candidates that describe lifespan extension in model organisms, data on longevity-inducing effects in higher organisms such as mice remain controversial or are missing. Furthermore, some of these candidates produce detrimental side effects such as immunosuppression or lactic acidosis, or have not been tested for safety in long-term studies. Up to now, there are no known ERM that could be recommended without limitations for use in humans.