A meta-analysis of potential biomarkers associated with microplastic ingestion in marine fish.

Over the past decade, global reports have shown a rise in the harmful effects of microplastics (MPs) on marine fish. This study analysed marine species' biochemical biomarker responses to microplastic exposure, finding that MPs can induce oxidative stress in marine fish through meta-regression results. Overall, exposure to MPs resulted in the activation of antioxidant defence mechanisms, such as superoxide dismutase, catalase and glutathione reductase, detoxification enzymes such as glutathione-S-transferase, the detection of malondialdehyde, and inhibition of acetylcholinesterase. Moreover, results highlight oxidative stress biomarkers were activated in wild species that had ingested MPs, indicating potential harm to marine fish, as confirmed in experimental studies. Furthermore, even though MPs' exposure is better regulated in an experimental setting, it is challenging to replicate actual exposure and environmental factors. The study's findings show the need for more investigation into the hazardous consequences of exposure to environmental MPs on species surveyed in the maritime environment.

Hospital Volume of Elective Abdominal Aortic Aneurysm Repair as a Predictor of Mortality After Ruptured Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Registry data suggest that centralising abdominal aortic aneurysm (AAA) surgery decreases the mortality rate after AAA repair. However, the impact of higher elective volumes on ruptured AAA (rAAA) repair associated mortality rates remains uncertain. This study aimed to examine associations between intact AAA (iAAA) repair volume and post-operative rAAA death. METHODS: Using data from official national registries between 2015 - 2019, all iAAA and rAAA repairs were separately analysed across 10 public hospitals. The following were assessed: 30 day and 12 month mortality rate following open surgical repair (OSR) and endovascular aneurysm repair (EVAR). Associations between the 5 year hospital iAAA repair volumes (organised into tertiles) and rAAA associated mortality rate were analysed, regardless of treatment modality. Receiver operating characteristic (ROC) curves were generated to identify iAAA volume thresholds for decreasing the rAAA mortality rate. Subanalysis by treatment type was conducted. Threshold analysis was repeated with the Markov chain Monte Carlo (MCMC) procedure to confirm the findings. RESULTS: A total of 1 599 iAAAs (80.2% EVAR, 19.8% OSR) and 196 rAAAs (66.3% EVAR, 33.7% OSR) repairs were analysed. The median and interquartile range of the volume/hospital/year for all iAAA repairs were 39.2 (31.2, 47.4). The top volume iAAA tertile exhibited lower rAAA associated 30 day (odds ratio [OR] 0.374; p = .007) and 12 month (OR 0.264; p < .001) mortality rates. The ROC analysis revealed a threshold of 40 iAAA repairs/hospital/year (EVAR + OSR) for a reduced rAAA mortality rate. Middle volume hospitals for open iAAA repair had reduced 30 day (OR 0.267; p = .033) and 12 month (OR 0.223; p = .020) mortality rates, with a threshold of five OSR procedures/year. The MCMC procedure found similar thresholds. No significant association was found between elective EVAR volumes and ruptured EVAR mortality. CONCLUSION: Higher iAAA repair volumes correlated with a lower rAAA mortality rate, particularly for OSR. The recommended iAAA repair threshold is 40 procedures/year and five procedures/year for OSR. These findings support high elective volumes for improving the rAAA mortality rate, especially for OSR.

Mitigating Age-Related Cognitive Decline and Oxidative Status in Rats Treated with Catechin and Polyphenon-60.

Aging is a normal physiological process influenced by the combination of multiple mechanisms, primarily oxidative stress and neuroinflammation, which impact general physiology and brain function. Phenolic compounds have demonstrated the ability to slow down the aging process of the brain due to their antioxidant and anti-inflammatory effects. This study assessed the protective properties of catechin and polyphenon-60 in non-pathologically aged rats regarding visuo-spatial learning and the oxidative status of the frontal cortex. Old animals were treated with catechin or green tea extract (polyphenon-60) for 36 days, daily. Healthy old and young rats were used as controls. During the first training phase, treated rats executed the test better, locating the target in less time compared with the controls. Biomarkers of oxidative stress (catalase activities, superoxide dismutase, glutathione reductase, and glutathione S-transferase) were reduced in the brain of old animals, although their activities were partially improved after both antioxidant treatments. Furthermore, the rise in the production of reactive oxygen species and malondialdehyde levels-a marker of lipid peroxidation-in the frontal cortex of aged animals was significantly ameliorated after the interventions. In conclusion, old rats exhibited enhanced cognitive function and reduced stress levels following the administration of catechin and polyphenon-60.

Circulating Neurofilament Light Chain Levels Increase with Age and Are Associated with Worse Physical Function and Body Composition in Men but Not in Women.

This study aimed to assess the relationship between age-related changes in Neurofilament Light Chain (NFL), a marker of neuronal function, and various factors including muscle function, body composition, and metabolomic markers. The study included 40 participants, aged 20 to 85 years. NFL levels were measured, and muscle function, body composition, and metabolomic markers were assessed. NFL levels increased significantly with age, particularly in men. Negative correlations were found between NFL levels and measures of muscle function, such as grip strength, walking speed, and chair test performance, indicating a decline in muscle performance with increasing NFL. These associations were more pronounced in men. NFL levels also negatively correlated with muscle quality in men, as measured by 50 kHz phase angle. In terms of body composition, NFL was positively correlated with markers of fat mass and negatively correlated with markers of muscle mass, predominantly in men. Metabolomic analysis revealed significant associations between NFL levels and specific metabolites, with gender-dependent relationships observed. This study provides insights into the relationship between circulating serum NFL, muscle function, and aging. Our findings hint at circulating NFL as a potential early marker of age-associated neurodegenerative processes, especially in men.

Hyperbaric Oxygen Therapy Reduces Oxidative Stress and Inflammation, and Increases Growth Factors Favouring the Healing Process of Diabetic Wounds.

Hyperbaric oxygen therapy (HBOT) is the clinical application of oxygen at pressures higher than atmospheric pressure. HBOT has been effectively used to manage diverse clinical pathologies, such as non-healing diabetic ulcers. The aim of the present study was to analyse the effects of HBOT on the plasma oxidative and inflammation biomarkers and growth factors in patients with chronic diabetic wounds. The participants received 20 HBOT sessions (five sessions/week), and blood samples were obtained at sessions 1, 5 and 20, before and 2 h after the HBOT. An additional (control) blood sample was collected 28 days after wound recovery. No significant differences were evident in haematological parameters, whereas the biochemical parameters progressively decreased, which was significant for creatine phosphokinase (CPK) and aspartate aminotransferase (AST). The pro-inflammatory mediators, tumour necrosis factor alpha (TNF-α) and interleukin 1ß (IL-1ß), progressively decreased throughout the treatments. Biomarkers of oxidative stress--plasma protein levels of catalase, extracellular superoxide dismutase, myeloperoxidase, xanthine oxidase, malondialdehyde (MDA) levels and protein carbonyls--were reduced in accordance with wound healing. Plasma levels of growth factors--platelet-derived growth factor (PDFG), transforming growth factor ß (TGF-ß) and hypoxia-inducible factor 1-alpha (HIF-1α)-- were increased as a consequence of HBOT and reduced 28 days after complete wound healing, whereas matrix metallopeptidase 9 (MMP9) progressively decreased with the HBOT. In conclusion, HBOT reduced oxidative and pro-inflammatory mediators, and may participate in activating healing, angiogenesis and vascular tone regulation by increasing the release of growth factors.

Antioxidant and anti-inflammatory potential of rhizome aqueous extract of sea holly (Eryngium maritimum L.) on Jurkat cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Eryngium is known for producing a wide range of bioactive compounds with proved medicinal properties. In the last years, research has focused on E. maritimum, with previous studies reporting anticancer, antimicrobial, antioxidant, and anti-inflammatory activities. Ethnobotanical literature suggests that it has been traditionally used to treat a wide range of illnesses, having antitussive, diuretic and aphrodisiac properties. Being rhizome one of the most bioactive organs, much of the available references from traditional uses suggest that it has been specifically used to treat renal diseases. In this sense, inflammation and oxidative processes play a major role in kidney dysfunctions, which could be associated to the mechanism of action of the plant extracts. AIM OF THE STUDY: The main aim of the study was to investigate the effects of E. maritimum rhizome extract on the antioxidant and inflammatory response in human immune cells. MATERIAL AND METHODS: Rhizome extracts were obtained from plants growing in Mallorca (Balearic Islands), and its composition was determined using HPLC-DAD, highlighting simple phenolic compounds such as trans-ferulic acid, catechin, chlorogenic acid, epicatechin and rosmarinic acid as the major constituents. Total antioxidant capacity was determined using the FRAP assay. Jurkat cells were cultured to analyse cytotoxicity by cell viability assay. In parallel, cells were stimulated with phytohemagglutinin and treated with different extract concentrations. Gene and protein expression, as well as nitrite and cytokine levels were evaluated as indicators of metabolic responses. RESULTS: The plant extract showed a high diversity of pharmacologically bioactive compounds with potential therapeutic uses. The extract presented null cytotoxicity and exerted antioxidant and anti-inflammatory effects on Jurkat cells by inducing an antioxidant response and reducing cytokine and nitric oxide release and the expression of pro-inflammatory genes. CONCLUSION: The present findings suggest that E. maritimum is a promising phytotherapeutic species because of its strong antioxidant and anti-inflammatory potential, which could explain some of its traditional uses.

A Biomarker Approach as Responses of Bioindicator Commercial Fish Species to Microplastic Ingestion: Assessing Tissue and Biochemical Relationships.

Plastic debris is a growing environmental problem on a global scale, as plastics and microplastics (MPs) can be ingested by marine organisms, inducing toxic effects. The aim of this study was to assess MP intake and antioxidant responses in three bioindicator species: red mullet, bogue, and anchovy (Mullus surmuletus, Boops boops, and Engraulis encrasicolus, respectively) for plastic contamination in the Mediterranean Sea. MP intake was assessed in the gastrointestinal tract of the fish. Further, several enzymes from both the liver and brain were analysed. The antioxidant defences, catalase (CAT) and superoxide dismutase (SOD), as well as the detoxifying enzyme glutathione-S-transferase (GST), were measured in both tissues. The acetylcholine esterase (AchE), as an indicator of neuronal damage, was measured in the brain. Malondialdehyde (MDA) was analysed as a marker of oxidative damage in the brain and liver samples. Total MP intake and MP typology differed between the three species, with M. surmuletus showing the lowest intake of MPs, while B. boops showed the highest intake of MPs. An increase in both antioxidant enzymes was evidenced in E. encrasicolus liver activity with respect to MP intake. In brain samples, an increase in CAT activity was found in M. surmuletus and B. boops as a consequence of MP ingestion. SOD activity in the brain increased in B. boops and E. encrasicolus that had ingested MPs. GST activity increased in the liver of M. surmuletus' and in brains of B. boops that had ingested MPs. The intake of MPs is species related, as well as being inherently linked to the habitat they live in and being able to induce a light activation of species-specific detoxifying and antioxidant mechanisms.

Multispecies Assessment of Anthropogenic Particle Ingestion in a Marine Protected Area.

We have applied a multispecies ecosystem approach to analyse the ingestion of anthropogenic particles (AP) in the gastrointestinal tract of 313 individuals (17 fish species and 8 invertebrate species) from pelagic, demersal and benthic habitats in a marine protected area off the Western Mediterranean (Cabrera National Park). We have quantified and characterized the ingestion at several taxonomic levels of fish, sea urchins, sea cucumbers, bivalves, and jellyfish in relation to biotic/abiotic factors based on taxonomic groups, trophic guilds (functional groups) and habitats. AP ingestion occurrence ranged from 26 to 100% with no significant differences among taxonomic groups. The fish within the MPA showed an overall ingestion occurrence ranging from 0 to 100%, the echinoderms from 29 to 100%, the bivalves from 72 to 96% and the jellyfish 36% ingestion. The ecosystem approach applied to evaluate overall AP ingestion within the species reported that for trophic guilds, the omnivorous species ingested the highest amounts of anthropogenic items, while herbivores ingested significantly fewer items than all other trophic guilds. Moreover, no significant differences were found amongst habitats, indicating a homogeneous spatial distribution of APs at all studied habitats. The multispecies approach provided insight into the high APs exposure to species within Cabrera MPA, highlighting the potential harm linked with marine litter that threatens marine biodiversity.

Equine Umbilical Cord Serum Composition and Its Healing Effects in Equine Corneal Ulceration.

Background: Human autologous serum (AS) and umbilical cord serum (UCS) both contain growth and neurotrophic factors that promote corneal healing. Aim: Our objectives were to compare equine AS and UCS cytokine and growth factor profiles and to assess the safety and clinical feasibility of the therapeutic use of UCS eye drops in cases of spontaneous complex ulcers. Study Design: Prospective clinical trial. Methods: Vitamin A insulin growth factor, platelet-derived growth factor-BB, transforming growth factor (TGF)-ß1 (enzyme-linked immunosorbent assay), interleukin (IL)-1ß, IL-6, interferon-γ, and monocyte chemoattractant protein 1 concentrations were determined in 10 AS collected from different horses and 10 UCS sampled at delivery. Six client-owned horses presenting with complex non-healing corneal defects of >5 mm2 were included in a clinical trial and treated with conventional therapy and conditioned UCS drops for 8-15 days. Ulcer surface and time to complete epithelialization were recorded. Results: Median concentrations of vitamin A, insulin growth factor, and platelet-derived growth factor-BB were not significantly different in AS compared with UCS (respectively, 14.5 vs. 12.05 µg/ml; 107.8 vs. 107.3 pg/ml; and 369.1 vs. 924.2 pg/ml). TGF-ß1 median concentration in UCS was significantly higher than in AS (3,245 vs. 2571pg/ml) (p = 0.04). IL-1ß, IL-6, interferon-γ, and monocyte chemoattractant protein 1 concentrations were variable in AS and undetectable in UCS. The corneal median ulcerative area was 37.2 mm2 (6.28-57.14 mm2) and had a duration of 4-186 days (median 19 days). All lesions healed within 13-42 days (median 17 days). No adverse effects nor recurrences within 1 month were noticed. Limitations: The sample size was small. Spontaneous corneal epithelial defects presented with variable clinical characteristics. There were no age-matched control horses to assess corneal healing time and rate. Conclusion and Clinical Significance: Equine UCS may be beneficial, as it contains no pro-inflammatory cytokines and a greater concentration of TGF-ß1 compared with AS. Topical UCS appears safe and may potentially be used as adjunctive therapy for equine complex non-healing ulcers.

Quantification of differential tissue biomarker responses to microplastic ingestion and plasticizer bioaccumulation in aquaculture reared sea bream Sparus aurata.

Marine aquaculture is considered a potential source of microplastics (MPs). MPs can induce oxidative stress and damage in marine species. In this study we evaluated the impact of MPs intake in the commercial fish, Sparus aurata, from aquaculture facilities and the antioxidant response associated to this MPs ingestion in caged specimens for 120 days. Sampling was carried out at the beginning of the study (T0), at 60 days (T60) and at 120 days (T120). At each sampling stage, gastrointestinal tract, blood, plasma, liver and muscle samples were obtained to analyse MPs intake (gastrointestinal tract), oxidative stress markers (blood, plasma and liver) and plasticizers bioaccumulation (muscle). Fish sampled at T60 presented the highest MPs intake and plasticizers accumulated in muscle over time, but with a different pattern according to type: bisphenols and phthalates. This indicates MPs ingestion induces a differential tissue response in S. aurata. Similarly, stress biomarkers presented a differential response throughout the study, depending on the analysed tissue. In the case of oxidative damage markers, for malondialdehyde (MDA) an increase throughout the study was observed both in liver and blood cells but with a progressive decrease in plasma. In the case of phase I detoxifying enzyme activities in liver, 7-ethoxyresorufin O-deethylase (EROD), 7-benzyloxy-4-[trifluoromethyl]-coumarin-O-debenzyloxylase (BFCOD) and carboxylesterases (CE), showed a comparable decrease at T60 with a slight recovery at T120. In contrast, glutathione-S-transferase (GST) activity was significantly enhanced at T60 compared to the other sampling stages. In conclusion, MPs ingestion occurs in aquaculture reared seabream where potentially associated plasticizers accumulate in the muscle and both could be responsible for plasma and liver oxidative stress damage and alterations on detoxifying biomarkers responses.

Assessment of the impact of aquaculture facilities on transplanted mussels (Mytilus galloprovincialis): Integrating plasticizers and physiological analyses as a biomonitoring strategy.

The growing plastic production and its continuous use is a significant problem. In addition, aquaculture practices have experienced a considerable growth and plastic is widely used in these activities, hence plasticizers must be considered due to their potential ecotoxicological impacts on species. Mussels placed inside an Integrated Multi-Trophic Aquaculture (IMTA) system and at two control locations were employed to quantify the ingestion of anthropogenic particles and associated chemical plasticizers, such as bisphenol A (BPA) jointly to bisphenol F (BPF) and bisphenol S (BPS), and phthalates represented by diethyl phthalate (DEP), dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP). In addition, some metabolism and oxidative stress related parameters were measured in mussels' whole soft tissue. Anthropogenic particle ingestion of mussels increased over time at the three locations and the following order of abundance of pollutants was observed: BPA> BPF> DEHP> DBP> BPS> DEP. Even though no differences according to location were found for pollutants' occurrence, time trends were evidenced for BPA and DEHP. On the other hand, a location effect was observed for biomarkers with highest values detected in mussels located at the vicinities of the aquaculture facility. In addition, a reduced detoxification activity was observed over time parallel to BPA decrease.

Anticancer properties of bromelain: State-of-the-art and recent trends.

Bromelain is a key enzyme found in pineapple (Ananas comosus (L.) Merr.); a proteolytic substance with multiple beneficial effects for human health such as anti-inflammatory, immunomodulatory, antioxidant and anticarcinogenic, traditionally used in many countries for its potential therapeutic value. The aim of this updated and comprehensive review focuses on the potential anticancer benefits of bromelain, analyzing the cytotoxic, apoptotic, necrotic, autophagic, immunomodulating, and anti-inflammatory effects in cancer cells and animal models. Detailed information about Bromelain and its anticancer effects at the cellular, molecular and signaling levels were collected from online databases such as PubMed/MedLine, TRIP database, GeenMedical, Scopus, Web of Science and Google Scholar. The results of the analyzed studies showed that Bromelain possesses corroborated pharmacological activities, such as anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair. Nonetheless, bromelain clinical studies are scarce and still more research is needed to validate the scientific value of this enzyme in human cancer diseases.

The Antioxidant Potential of the Mediterranean Diet as a Predictor of Weight Loss after a Very Low-Calorie Ketogenic Diet (VLCKD) in Women with Overweight and Obesity.

Obesity involves a chronic state of low-grade inflammation, which is linked to the development of several comorbidities. Recently, the very low-calorie ketogenic diet (VLCKD) has gained great interest in the treatment of obesity, almost ousting the ancient and healthy Mediterranean diet (MD). However, because these dietary regimens exploit different pathophysiological mechanisms, we hypothesize that adherence to the MD may play a role in determining the efficacy of the VLCKD. We enrolled 318 women (age 38.84 ± 14.37 years; BMI 35.75 ± 5.18 kg/m²) and assessed their anthropometric parameters, body compositions, and adherence to the MD (with the PREvención con DIetaMEDiterránea (PREDIMED) questionnaire) at baseline. The anthropometric parameters and body composition were repeated at the end of the VLCKD. At the end of the VLCKD, the women with high adherence to the MD achieved the best results in terms of weight loss and improved body composition. Specifically, the women who were above the median of fat mass (FM)% reduction had the best MD pattern, characterized by a higher consumption of extra virgin olive oil (EVOO), fruits, vegetables, and red wine, as well as a higher adherence to the MD than the women who were below the same median. In a multiple regression analysis, the PREDIMED score was the main predictor of the FM% reduction score and came in first, followed by fruit, EVOO, and glasses of wine, in predicting the percentage reduction in FM. A PREDIMED score value of > 5 could serve as a threshold to identify patients who are more likely to lose FM at the end of the VLCKD. In conclusion, high adherence to the MD resulted in higher VLCKD efficacy. This could be due to the antioxidant and anti-inflammatory properties of the MD, which are capable of establishing a metabolic set-up that is favorable to the onset of more effective ketosis.

5-Dodecanolide, a Compound Isolated from Pig Lard, Presents Powerful Anti-Inflammatory Properties.

BACKGROUND: Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could be responsible for the anti-inflammatory effects. METHODS: The anti-inflammatory effects of PL were tested in a rat model of zymosan-induced hind paw inflammation. Further, the hydroalcoholic extract from PL was obtained, the composition analyzed, and the anti-inflammatory activity of the extracts and isolated components assayed using immune cells stimulated with lipopolysaccharide (LPS). RESULTS: Applying the ointment on the inflamed rat feet reduced the foot diameter, foot weight, and activities of antioxidant enzymes and inflammatory markers of circulating neutrophils. The main components of the hydroalcoholic extract were 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, hexadecanamide, and resolvin D1. CONCLUSIONS: PL reduces the immune response in an animal model stimulated with zymosan. Hydroalcoholic PL extract and its components (5-Dodecanolide, Oleamide, and Resolvin D1) exerted an anti-inflammatory effect on LPS-stimulated neutrophils and peripheral mononuclear cells reducing the capability to produce TNFα, as well as the activities of antioxidant and pro-inflammatory enzymes. These effects are attributable to 5-dodecanolide, although the effects of this compound alone do not reach the magnitude of the anti-inflammatory effects observed by the complete hydroalcoholic extract.

Polycystic ovary syndrome and cardiovascular risk. Could trimethylamine N-oxide (TMAO) be a major player? A potential upgrade forward in the DOGMA theory.

Several studies reported an increase in cardiovascular risk (CVR) in women with polycystic ovary syndrome (PCOS), considered primarily as the result of the combination of all the clinical features that characterize the syndrome, including hyperandrogenism, insulin resistance, diabetes, obesity chronic low-grade inflammation. Interestingly, in 2012 it has been proposed the so-called DOGMA theory, suggesting the pivotal role played by microbiota alteration in the development of PCOS. Subsequently, several authors evidenced the existence in PCOS women of a marked dysbiosis, which is related to the development of metabolic diseases and cardiovascular complications, mainly due to the production of bacteria-derived metabolites that interfere with various pathways. Among these, trimethylamine-N-oxide (TMAO) is emerging as one of the most important and studied microbiota-derived metabolites related to the increase in CVR, due to its pro-atherosclerotic effect. The purpose of the present review is to summarize the evidence in order to support the hypothesis that, in women with PCOS, dysbiosis might be further involved in enhancement of the CVR via contributing to the increase of circulating TMAO. Although no observational studies on a large number of patients directly investigated the serum levels of TMAO in PCOS women, this manuscript aimed to drive future studies in this field, concurring in providing a novel approach for both comprehension and treatment of the CVR in PCOS.

An Update of Anthraquinone Derivatives Emodin, Diacerein, and Catenarin in Diabetes.

Diabetes is part of metabolic diseases and is characterized by high blood sugar levels over a prolonged period as result of an insulin-deficient production or an inappropriate response to insulin by our cells. This chronic disease was the direct cause of 1.6 million deaths in 2016 as reported by the World Health Organization. Emodin is a natural product and active ingredient of various Chinese herbs with the chemical formula 1,3,8-trihydroxy-6-methylanthraquinone. Diacerein is another naturally occurring anthraquinone (1,8-diacetoxy-3-carboxyanthraquinone) commonly used as commercial drug to treat osteoarthritis. These two anthraquinone derivatives have been shown to exert antidiabetic activities. Emodin seems to enhance the glucose tolerance and insulin sensibility via activation of PPARγ and modulation of metabolic-related genes. Diacerein seems to decrease inflammatory cytokines and increase insulin secretion enhancing insulin sensibility and therefore improving glucose control. Other naturally occurring anthraquinone derivatives, such as catenarin (1,4,6,8-tetrahydroxy-3-methylanthraquinone), have been shown to have antidiabetic activities although few studies have been performed. The synthesis of new emodin derivatives is increasing, but these new molecules have not been tested for diabetes treatment. In the current work, available literature on anthraquinone derivatives' effects in diabetes disease is reviewed. Moreover, we discuss the chemistry, food sources, bioavailability, and toxicity of the naturally occurring anthraquinone with antidiabetic effects.

The neuroprotective effects of polyphenols, their role in innate immunity and the interplay with the microbiota.

Neurodegenerative disorders, particularly in the elderly population, represent one of the most pressing social and health-care problems in the world. Besides the well-established role of both oxidative stress and inflammation, alterations of the immune response have been found to be closely linked to the development of neurodegenerative diseases. Interestingly, various scientific evidence reported that an altered gut microbiota composition may contribute to the development of neuroinflammatory disorders. This leads to the proposal of the concept of the gut-brain-immune axis. In this scenario, polyphenols play a pivotal role due to their ability to exert neuroprotective, immunomodulatory and microbiota-remodeling activities. In the present review, we summarized the available literature to provide a scientific evidence regarding this neuroprotective and immunomodulatory effects and the interaction with gut microbiota of polyphenols and, the main signaling pathways involved that can explain their potential therapeutic application in neurodegenerative diseases.