The Role of Nutrition During the COVID-19 Pandemic: What We Know.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) (COVID-19) infection provokes serious clinical consequences, which in many situations need hospitalization of the patient in Intensive Care Unit. Additionally, SARS-COV-2 infection can indirectly cause deaths in aged individuals as well as in patients with co-morbidities. OBJECTIVE: To evaluate the effects of nutrition during the COVID-19 pandemic in both hospitalized patients and the general population. METHODS: Authors searched Medline (PubMed), Web of Science, EMBASE, Cochrane Library, Google, and Institutional websites for medical subheadings terms and free full text referred to "SARS-CoV-2", COVID-19", "nutrition", "immune system", before 31st July 2020. RESULTS: A total of 20 articles describing different nutritional interventions for patients with SARS-- CoV-2 infection focusing on the general population have been included. Of these, 6 studies are dealing with nutritional interventions for patients with SARS-CoV2 infection. The others are focalized on a potential beneficial effect exerted by a Mediterranean diet (MD), related to the supplementation of micronutrients and vitamins. CONCLUSION: A correct lifestyle, including the consumption of nutrients largely present in MD, may be beneficial for preventing or improving prognosis in the SARS-CoV-2 infection.

Red Grape Polyphenol Oral Administration Improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis.

BACKGROUND: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce the release of proinflammatory cytokines and nitric oxide (NO), while increasing the levels of interleukin (IL)-10, an anti-inflammatory cytokine. OBJECTIVE: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. METHODS: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). The other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups, seven dropouts were recorded. RESULTS: At T1 in comparison to T0, in treated patients, values of interferon-γ, IL-4, IL-17, pentraxin 3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo- treated patients, no modifications of biomarkers were evaluated at T1. CONCLUSION: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.

Exploitation of Some Natural Products for the Prevention and/or Nutritional Treatment of SARS-CoV2 Infection.

Dietary habits strongly influence our health status, mostly in terms of maintenance of the inflammatory/anti-inflammatory homeostasis. High fat and high sugar diets account for the development of a low-grade inflammation, which is the pathogenic common denominator of various chronic diseases. Severe Acute Respiratory Syndrome Coronavirus (SARS)-CoV2 (COVID-19) infection affects all ages and especially frail elderly people and a nutritional intervention seems to be crucial in the course of this pandemic. The present review describes the properties of some vegetal products and their derivatives, such as Lupin sp., garlic, salvia and extra virgin olive oil (EVOO) that can be exploited for their beneficial effects, as preventive and/or nutritional treatment of coronavirus disease SARS-CoV2. Lupin, salvia, garlic and EVOO share overlapping properties, such as anti-oxidant, anti-inflammatory and anti-viral activities. Quite importantly, these products and their derivatives are able to recover the expression of angiotensin converting enzyme expression 2 on cell membrane, otherwise suppressed by COVID-19 binding and entry into cytoplasm. Dietary administration of the above nutraceuticals or their extracts may play a preventive or nutritional role in the course of SARS-CoV2 infection, even including the effects of the lockdown and the condition of inflamm-ageing.

Protective Effects of Eicosapentaenoic Acid Plus Hydroxytyrosol Supplementation Against White Adipose Tissue Abnormalities in Mice Fed a High-Fat Diet.

OBJECTIVE: Obesity induced by high-fat diet (HFD) elicits white adipose tissue dysfunction. In this study, we have hypothesized that the metabolic modulator eicosapentaenoic acid (EPA) combined with the antioxidant hydroxytyrosol (HT) attenuates HFD-induced white adipose tissue (WAT) alterations. METHODS: C57BL/6J mice were administered with a HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg/kg/day), HT (5 mg/kg/day), or both for 12 weeks. Determinations in WAT include morphological parameters, EPA and docosahexaenoic acid content in phospholipids (gas chromatography), lipogenesis, oxidative stress (OS) and inflammation markers, and gene expression and activities of transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65 subunit) and nuclear factor erythroid 2-related factor 2 (Nrf2) (quantitative polymerase chain reaction and enzyme linked immunosorbent assay). RESULTS: HFD led to WAT hypertrophy in relation to PPAR-γ downregulation. WAT metabolic dysfunction was characterized by upregulation of lipogenic SREBP-1c system, mitochondrial energy metabolism depression, loss of the antioxidant Nrf2 signaling with OS enhancement, n-3 long-chain polyunsaturated fatty acids depletion and activation of the pro-inflammatory NF-κB system. EPA and HT co-supplementation diminished HFD-dependent effects additively, reaching values close or similar to controls. CONCLUSION: Data presented strengthen the importance of combined protocols such as EPA plus HT to attenuate metabolic-inflammatory states triggered by obesity.

Peripheral Immunosenescence and Central Neuroinflammation: A Dangerous Liaison - A Dietary Approach.

BACKGROUND & OBJECTIVES: In old people, both innate and adaptive immune responses are impaired, thus leading to a condition of systemic inflamm-ageing, even including the involvement of the central nervous system (CNS). AIMS: Here, main mechanisms of the immune ageing and neuro-inflammation will be discussed along with the dietary approaches for the modulation of age related diseases. DISCUSSION: Neuroinflammation is caused by the passage of inflammatory mediators through the brain blood barrier to CNS. Then, in the brain, antigenic stimulation of microglia and/or its activation by peripheral cytokines lead to a robust production of free radicals with another wave of proinflammatory cytokines which, in turn, causes massive neuronal damage. Also, infiltrating T cells [T helper (h) and T cytotoxic cells] contribute to neuronal damage. Additionally, a peripheral imbalance between inflammatory Th17 cells and anti-inflammatory T regulatory cells seems to be prevalent in the aged brain, thus leading to a proinflammatory profile. Alzheimer's disease, Parkinson's disease and multiple sclerosis will be described as typical neurodegenerative diseases. Finally, modulation of the immune response thanks to the anti-oxidant and anti-inflammatory effects exerted by dietary products and nutraceuticals in ageing will be discussed. Special emphasis will be placed on polyunsaturated fatty acids, polyphenols, micronutrients and pre-probiotics and synbiotics. CONCLUSION: Ageing is characterized by an imbalance subversion of the immune system with a condition of inflamm-ageing. Neuroinflammation and neurodegenerative diseases seem to be a central manifestation of a peripheral perturbation of the immune machinery. Dietary products and nutraceuticals may lead to a down-regulation of the oxidative and pro-inflammatory profile in ageing.

Effects of Polyphenol Administration to European Farmed Sea Bass (Dicentrharcus labrax L.): Special Focus on Hepatopancreas Morphology.

BACKGROUND AND OBJECTIVE: Hepatopancreas is an accessory organ associated with the liver in some fish, even including sea bass (Dicentrharcus labrax L.). Hepatopancreas contains an exocrine portion but until now its function has poorly been investigated. METHODS: Here, European farmed sea bass have been treated with a feed enriched in polyphenols extracted from seeds of red grape (Nero di Troia cultivar) at two different doses (100 and 200 mg/kg, respectively) from day 273 to day 323. In fish samples, hepatopancreas area sizes have been measured to evaluate the effects of this dietary regimen on its morphology. RESULTS: Quite interestingly, in treated fish area sizes of hepatopancreas were higher than those detected in untreated fish. Two hundred mg dose of polyphenols was more effective than that of 100 mg/kg polyphenols. Finally, hepatic polyphenol concentration was diminished in fish receiving 100 mg dose polyphenols and normalized with 200 mg dose in comparison to untreated fish. This evidence suggests the utilization of polyphenols for liver function, even including hepatopancreas development. CONCLUSION: Our data suggest an expansion of hepatopancreas induced by polyphenol administration that is also associated with less mortality in farmed fish.

Antimicrobial Peptides in Human Disease: Therapeutic Approaches. Second of Two Parts.

Antimicrobial Peptides (AMPs) are produced by a variety of human immune and non immune cells in health and disease. In virtue of their antimicrobial activity, AMPs have been exploited in human disease and here this aspect will extensively be described. AMPs in comparison to antibiotics possess a larger spectrum of antimicrobial activity without inducing microbial resistance. Therefore, their use in the course of antibiotic-resistant infections is justified. AMP activity in early life, in the airways, in the oral and gastro-enteric system, in the skin and in the female reproductive tract, respectively, will be elucidated. In addition, the use of AMPs in sepsis will be discussed due to the frequency of this pathological condition characterized by multiple organ dysfunctions. Finally, the evidence that AMPs represent valid substitutes of antibiotics will be provided and a series of novel substances able to reinforce the innate immune response in different clinical settings will be discussed.

Olive Leaf Extracts Act as Modulators of the Human Immune Response.

BACKGROUND: Olive tree leaves have been used in the Mediterranean area as traditional medicine in virtue of their healthy effects. Olive leaf extracts (OLEs) contain higher amounts of polyphenols than those detected in the extra virgin olive oil and fruit. Several lines of evidence support the cardioprotective, anti-oxidant and anti-inflammatory activities exerted by OLEs. METHODS: Peripheral blood mononuclear cells from twenty-five healthy donors were cultured in the presence of 3 µg of two OLE extracts, extract A (resuspended in water) and extract B (resuspended in 70% ethanol). After harvesting, cell pellets were used for cytofluorimetric phenotyping, while supernatants were assayed for cytokine release by means of ELISA. Furthermore, in the same supernatants nitric oxide (NO) content was determined. RESULTS: Both extracts, but especially extract A, increased absolute numbers of CD8+ and natural killer (NK) cells. In addition, an increased production of interferon (IFN)-γ by both extracts as an expression of T helper (h)1 activation was observed. Finally, both extracts enhanced NO release. CONCLUSION: OLEs, and mostly extract A, are able to in vitro modify healthy human immune response by increasing IFN-γ production which seems to be associated to the higher absolute numbers of CD8+ and NK cells and this may suggest a reinforcement of the anti-tumor activity. Furthermore, increased levels of NO may indicate the potential cardioprotective effects exerted by OLEs in virtue of their vasodilation dependent activity. Finally, OLEs are able to maintain the equilibrium between T regulatory cells and Th17 cells as evidenced by unmodified levels of interleukin (IL)-IL-10 and IL-17, respectively. In the light of these results, OLEs are potential therapeutic compounds for the treatment of chronic inflammatory disease, also preventing cardiovascular event outcome.

In vitro Effects of Polyphenols on the Peripheral Immune Responses in Nickel-sensitized Patients.

BACKGROUND: Nickel (Ni) is a metal largely present in the environment and prolonged exposure to it may lead to multiple pathological conditions in human subjects. Among these, the most frequent is allergic contact dermatitis. METHODS: Peripheral blood mononuclear cells isolated from 25 patients with Ni-dependent contact dermatitis were evaluated in terms of cytokine release and nitric oxide (NO) production in the presence or absence of two doses (3 and 5 µg, respectively) of polyphenols. RESULTS: Polyphenols were able to reduce the increased release of interferon-γ and interleukin (IL)-4, while maintaining the equilibrium between IL-10 and IL-17. At the same time, exaggerated release of NO was reduced by polyphenol supplementation. CONCLUSION: In view of their anti-inflammatory activities, polyphenols may represent a potential therapeutic tool to treat Ni-sensitized patients.

In Vitro Effects of Nickel on Healthy Non-Allergic Peripheral Blood Mononuclear Cells. The Role of Red Grape Polyphenols.

BACKGROUND: Nickel (Ni) is widely distributed in the environment and continuous exposure to this metal may lead to pathological manifestations, such as the human allergic contact dermatitis. METHODS: The in vitro effects of Ni on human healthy non allergic peripheral blood mononuclear cells (PBMCs) in the absence or presence of red grape polyphenols have been evaluated. In the culture supernatants, levels of cytokines have been determined by ELISA, while nitric oxide (NO) concentration has been evaluated by a colorimetric procedure. RESULTS: Ni per se did not affect release of interferon-γ, interleukin (IL)-4 and IL-10. Instead, this metal dramatically reduced production of IL-17 which was restored by the supplementation of polyphenols. Finally, while Ni significantly increased generation of NO, polyphenols reduced production of this compound. CONCLUSION: Taken together, all these data may indicate a preventative role of polyphenols against Ni exposure in non allergic to Ni individuals, also confirming the immunomodulating role of these natural products. The interaction Ni/polyphenols/lipopolysaccharides will also be discussed.

Cigarette Smoke-mediated Perturbations of the Immune Response: A New Therapeutic Approach with Natural Compounds.

Cigarette smoke (CS) accounts for the outcome of several pathologies, even including lung cancer, cardiovascular disease and chronic obstructive pulmonary disease (COPD). Under healthy conditions, lung immune system becomes tolerant in response to various external stimuli. CS exposure alters the pulmonary immune equilibrium, thus leading to a condition of hyper activation of the local innate and adaptive immunity. COPD is one of the major complications of chronic CS exposure where a pro-inflammatory profile of the pulmonary and systemic immunity is predominant. In this review, alternative treatments with natural products to mitigate CS-mediated pulmonary inflammation are proposed. In particular, polyphenols, a class of natural compounds largely present in fruits and vegetables, have been shown to act as anti-inflammatory agents. Accordingly, recent experimental and clinical evidences support polyphenol-mediated potential health benefits in smokers. For instance, pomegranate juice is able to attenuate the damage provoked by CS on cultured human alveolar macrophages. In addition, maqui beery extract has been proven to normalize H2O2 and interleukin-6 levels in exhaled breath condensate in healthy smokers. However, some limitations of alternative treatments are represented by a better knowledge of the mechanism(s) of action exerted by polyphenols and by the lack of animal models of COPD. In any case, the potential targets of polyphenols in the course of COPD will be outlined with special reference to the activation of T regulatory cells as well as to the inhibition of the polymorphonuclear cell and monocyte respiratory burst and of the NF-κB pathway, respectively.

Role of Immune Cells in the Course of Central Nervous System Injury: Modulation with Natural Products.

Immune cells actively participate to the central nervous system (CNS) injury either damaging or protecting neural tissue with release of various mediators. Residential microglia and monocyte-derived macrophages play a fundamental role within the injured CNS and, here, special emphasis will be placed on M1 and M2 macrophages for their different functional activities. On the other hand, peripheral T regulatory (Treg) cells exert antiinflammatory activities in the diseased host. In this respect, activation of Treg cells by nutraceuticals may represent a novel approach to treat neuroinflammation. Omega-3 fatty acids and polyphenols will be described as substances endowed with antioxidant and anti-inflammatory activities. However, taking into account that Treg cells act in the later phase of CNS injury, favoring immune suppression, manipulation of host immune system with both substances requires caution to avoid undesired side effects.

Disorders of innate immunity in human ageing and effects of nutraceutical administration.

Immune decline with ageing accounts for the increased risk of infections, inflammatory chronic disease, autoimmunity and cancer in humans. Both innate and adaptive immune functions are compromised in aged people and, therefore, attempts to correct these dysfunctions represent a major goal of modern medicine. In this review, special emphasis will be placed on the aged innate immunity with special reference to polymorphonuclear cell, monocyte/ macrophage, dendritic cell and natural killer cell functions. As potential modifiers of the impaired innate immunity, some principal nutraceuticals will be illustrated, such as micronutrients, pre-probiotics and polyphenols. In elderly, clinical trials with the above products are scanty, however, some encouraging effects on the recovery of innate immune cells have been reported. In addition, our own results obtained with symbiotics and polyphenols extracted from red wine or fermented grape marc suggest the potential ability of these substances to modulate the innate immune response in ageing, thus reducing the inflammaging which characterizes immune senescence.

Human use of Leucoselect® Phytosome® with special reference to inflammatory-allergic pathologies in frail elderly patients.

Human ageing is characterized by several abnormalities of both innate and adaptive immune responses, thus leading to an increased frequency of infectious, inflammatory, allergic and autoimmune diseases. In elderly patients, among allergic diseases, asthma is a very common pathological event which complicates the dysfunction of many systems. Among a variety of natural products used to modulate the altered immune response, polyphenols have been shown to exert antiinflammatory activities in both young and aged persons. Here, special emphasis will be given to the the immune-modulating effects of Leucoselect® Phytosome® (a dietary supplement enriched in the flavonoid epigallocatechin) administered to frail elderly patients. Leucoselect® Phytosome® was able to upregulate the T helper (Th)1 response [increase in serum concentrations of interleukin (IL)-2 and interferon-γ]. On the other hand, IL-4 serum levels, as an index of Th2 function, fluctuated within normal ranges. Quite interestingly, in this cohort of frail aged patients from South Italy the balance between inflammation (IL-17) and anti-inflammation (IL-10) was preserved, thus suggesting that the Mediterranean diet might have been involved in the observed effects. In conclusion, these data support the ability of Leucoselect® Phytosome® to induce up-regulation of Th1 responses in frail elderly patients which may be beneficial in those patients affected by chronic allergic disorders.

Functional foods and nutraceuticals as therapeutic tools for the treatment of diet-related diseases.

In Western societies, the incidence of diet-related diseases is progressively increasing due to greater availability of hypercaloric food and a sedentary lifestyle. Obesity, diabetes, atherosclerosis, and neurodegeneration are major diet-related pathologies that share a common pathogenic denominator of low-grade inflammation. Functional foods and nutraceuticals may represent a novel therapeutic approach to prevent or attenuate diet-related disease in view of their ability to exert anti-inflammatory responses. In particular, activation of intestinal T regulatory cells and homeostatic regulation of the gut microbiota have the potential to reduce low-grade inflammation in diet-related diseases. In this review, clinical applications of polyphenol-rich functional foods and nutraceuticals in postprandial inflammation, obesity, and ageing will be discussed. We have placed special emphasis on polyphenols since they are broadly distributed in plants.