Phytochemical Analysis and In Vitro Antileukemic Activity of Alkaloid-Enriched Extracts from Vinca sardoa (Stearn) Pignatti.

Vinca sardoa (Stearn) Pignatti, known as Sardinian periwinkle, is widely diffused in Sardinia (Italy). This species contains indole alkaloids, which are known to have a great variety of biological activities. This study investigated the antileukemic activity against a B lymphoblast cell line (SUP-B15) of V. sardoa alkaloid-rich extracts obtained from plants grown in Italy, in Iglesias (Sardinia) and Rome (Latium). All the extracts showed a good capacity to induce reductions in cell proliferation of up to 50% at the tested concentrations (1-15 µg/mL). Moreover, none of the extracts showed cytotoxicity on normal cells at all the studied concentrations.

Dietary antioxidants, non-enzymatic antioxidant capacity and the risk of osteoarthritis in the Swedish National March Cohort.

PURPOSE: Oxidative stress might play an important role in the development of osteoarthritis, but not much is known about the effect of antioxidants on osteoarthritis risk. We, therefore, aimed to investigate the effect of dietary vitamin C, E, beta-carotene, and non-enzymatic antioxidant capacity (NEAC), which measures overall antioxidant activity from the diet, on the risk of osteoarthritis. METHODS: For this study 43,865 men and women from the Swedish National March Cohort (SNMC) were followed for up to 19 years. We computed dietary intake of vitamin C, E and beta-carotene using information from a Food Frequency Questionnaire (FFQ). To estimate dietary NEAC we combined the information from the FFQ with food item-specific antioxidant capacity values from an antioxidant food database. Cases of osteoarthritis were identified through the Swedish National Patient Registers. We categorized all exposure variables into sex-specific quartiles and used multivariable-adjusted Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: In total, we observed 5976 cases of OA during 469,148 person-years of follow-up. After adjusting for potential confounders, we did not find any association between vitamin C, beta-carotene and NEAC (p-values for trend > 0.5), but a positive association was found with higher dietary vitamin E intake (HR Q4 vs Q1: 1.11; 95% CI 1.02-1.21; p for trend = 0.01) and the risk of OA. CONCLUSION: Our findings do not provide evidence for dietary antioxidants to protect from the development of OA, and a higher dietary vitamin E intake might even increase the risk.

Roles and competencies in the nutritional domain for the management of the metabolic diseases and in the hospital setting: A position paper of the Italian College of Academic Nutritionists, MED-49 (ICAN-49).

Epidemiological evidence has confirmed the potential causal relationship between specific dietary factors and non-communicable diseases. However, currently nutrition was shown to be insufficiently integrated into medical education, regardless of the country. Without an adequate nutrition education, it is reasonable to assume that future physicians, as well as other health care professionals, will be not able to provide the highest quality care to patients in preventing and treating non-communicable diseases. Furthermore, the insufficient availability of physicians with specializations in nutrition has posed the basis for the development of non-medical careers in the field of nutrition. The present document was drafting by the Italian College of Academic Nutritionists, MED-49 (ICAN-49), with the aim to provide an overview on the nutritional competency standards covered by several health care professionals (Physicians Clinical Nutrition Specialists, Clinical Dietitians, Professional Clinical Nutrition Specialists, etc) for the prevention of diseases and/or support of pharmacological therapies. The aim of the ICAN 49 is to suggest a major shift in practice opportunities and roles for many nutritionists, especially for the management of the metabolic diseases, and promote a paradigm change: a clinical and educational leadership role for Physician Clinical Nutrition Specialists in the hospital setting.

The Genus Haplophyllum Juss.: Phytochemistry and Bioactivities-A Review.

Herein, a comprehensive review is given focusing on the chemical profiles of the essential oils (EOs), non-volatile compounds, ethnobotany, and biological activities of different Haplophyllum (Rutaceae family) species. To gather the relevant data, all the scientific databases, including Scopus, ISI-WOS (Institute of Scientific Information-Web of Science), and PubMed and highly esteemed publishers such as Elsevier, Springer, Taylor and Francis, etc., were systematically retrieved and reviewed. A wide array of valuable groups of natural compounds, e.g., terpenoids, coumarins, alkaloids, lignans, flavonoids, and organic acids have been isolated and subsequently characterized in different organic extracts of a number of Haplophyllum species. In addition, some remarkable antimicrobial, antifungal, anti-inflammatory, anticancer, cytotoxic, antileishmanial, and antialgal effects as well as promising remedial therapeutic properties have been well-documented for some species of the genus Haplophyllum.

Phytochemical Analysis and Trypanocidal Activity of Marrubium incanum Desr.

The rationale inspiring the discovery of lead compounds for the treatment of human parasitic protozoan diseases from natural sources is the well-established use of medicinal plants in various systems of traditional medicine. On this basis, we decided to select an overlooked medicinal plant growing in central Italy, Marrubium incanum Desr. (Lamiaceae), which has been used as a traditional remedy against protozoan diseases, and to investigate its potential against Human African trypanosomiasis (HAT). For this purpose, we assayed three extracts of different polarities obtained from the aerial parts of M. incanum-namely, water (MarrInc-H2O), ethanol (MarrInc-EtOH) and dichloromethane (MarrInc-CH2Cl2)-against Trypanosoma brucei (TC221), with the aim to discover lead compounds for the development of antitrypanosomal drugs. Their selectivity index (SI) was determined on mammalian cells (BALB/3T3 mouse fibroblasts) as a counter-screen for toxicity. The preliminary screening selected the MarrInc-CH2Cl2 extract as the most promising candidate against HAT, showing an IC50 value of 28 µg/mL. On this basis, column chromatography coupled with the NMR spectroscopy of a MarrInc-CH2Cl2 extract led to the isolation and identification of five compounds i.e. 1-α-linolenoyl-2-palmitoyl-3-stearoyl-sn- glycerol (1), 1-linoleoyl-2-palmitoyl-3-stearoyl-sn-glycerol (2), stigmasterol (3), palmitic acid (4), and salvigenin (5). Notably, compounds 3 and 5 were tested on T. brucei, with the latter being five-fold more active than the MarrInc-CH2Cl2 extract (IC50 = 5.41 ± 0.85 and 28 ± 1.4 µg/mL, respectively). Furthermore, the SI for salvigenin was >18.5, showing a preferential effect on target cells compared with the dichloromethane extract (>3.6). Conversely, stigmasterol was found to be inactive. To complete the work, also the more polar MarrInc-EtOH extract was analyzed, giving evidence for the presence of 2″-O-allopyranosyl-cosmosiin (6), verbascoside (7), and samioside (8). Our findings shed light on the phytochemistry of this overlooked species and its antiprotozoal potential, providing evidence for the promising role of flavonoids such as salvigenin for the treatment of protozoal diseases.

Nor-Lignans: Occurrence in Plants and Biological Activities-A Review.

In this review article, the occurrence of nor-lignans and their biological activities are explored and described. Nor-lignans have proven to be present in several different families also belonging to chemosystematically distant orders as well as to have many different beneficial pharmacological activities. This review article represents the first one on this argument and is thought to give a first overview on these compounds with the hope that their study may continue and increase, after this.

Higher Dietary Non-enzymatic Antioxidant Capacity Is Associated with Decreased Risk of All-Cause and Cardiovascular Disease Mortality in Japanese Adults.

BACKGROUND: Few studies have assessed associations of non-enzymatic antioxidant capacity (NEAC) in the overall diet with all-cause or specific mortality, and their results have been inconsistent. OBJECTIVES: The present study investigated the association between dietary NEAC and all-cause or cause-specific mortality. METHODS: The study was a large-scale population-based prospective cohort study in Japan consisting of 42,520 men and 50,207 women aged 44-76 y, who had no history of cancer, stroke, ischemic heart disease, or chronic liver disease. We evaluated FFQ-based dietary NEAC with use of published databases in which the NEACs of individual foods were analyzed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Dietary NEAC was calculated by multiplying the estimated NEAC with the consumed amount and summing up those values for all foods, and was categorized in quartiles. We identified death and cause of death with use of residential registry and death certificates. HRs and 95% Cls for death from the second survey, which was conducted from April 1995 to December 2014 were estimated with Cox proportional hazards regression analysis. RESULTS: After 1,498,308 person-years of follow-up, 12,978 total deaths occurred. The multivariable-adjusted HRs (95% Cls) for all-cause mortality for the highest compared with the lowest quartile of FRAP and ORAC were 0.85 (0.80, 0.89) and 0.84 (0.79, 0.89), respectively. Dietary NEACs were inversely associated with mortality from cardiovascular disease (CVD), but not from cancer. The multivariable-adjusted HRs (95% Cls) for CVD for the highest compared with the lowest quartile of FRAP and ORAC were 0.83 (0.75, 0.92) and 0.79 (0.70, 0.89), respectively. CONCLUSIONS: Higher dietary NEACs from FRAP and ORAC were associated with lower risk of all-cause mortality and mortality from CVD in Japanese adults.

Dietary non enzymatic antioxidant capacity and the risk of myocardial infarction in the Swedish women's lifestyle and health cohort.

Foods rich in antioxidants have been associated with a reduced risk of myocardial infarction. However, findings from randomized clinical trials on the role of antioxidant supplementation remain controversial. It has been suggested that antioxidants interact with each other to promote cardiovascular health. We therefore investigated the association between dietary Non Enzymatic Antioxidant Capacity (NEAC), measuring the total antioxidant potential of the whole diet, and the risk of myocardial infarction. We followed 45,882 women aged 30-49 years and free from cardiovascular diseases through record linkages from 1991 until 2012. Dietary NEAC was assessed by a validated food frequency questionnaire collected at baseline. Total dietary NEAC was categorized into quintiles and multivariable Cox proportional hazard regression models were fitted to estimate hazard ratios (HR) with 95% confidence intervals (CI). During a mean follow-up time of 20.3 years we detected 657 incident cases of myocardial infarction. After adjusting for potential confounders, we found a significant 28% lower risk of myocardial infarction among women in the fourth (HR: 0.72; 95% CI 0.55-0.95) and a 40% lower risk among women in the fifth quintile (HR: 0.60, 95% CI 0.45-0.81) of dietary NEAC compared to women in the first quintile, with a significant trend (p-value < 0.001). Higher dietary NEAC is associated with a lower risk of myocardial infarction in young to middle-aged women. These findings support the hypothesis that dietary antioxidants protect from myocardial infarction and that this effect might be exerted through interactions between antioxidants.

The Validity and Reproducibility of Dietary Non-enzymatic Antioxidant Capacity Estimated by Self-administered Food Frequency Questionnaires.

BACKGROUND: High dietary non-enzymatic antioxidant capacity (NEAC) has been inversely related to the incidence of degenerative diseases. However, few studies have investigated the validity and reproducibility of dietary NEAC estimated from a food frequency questionnaire (FFQ). We assessed the validity and reproducibility of FFQ-based dietary NEAC against a dietary record (DR). METHODS: Participants were 244 men and 253 women who completed a 28-day DR and FFQs. NEAC for each food item was estimated according to available databases of antioxidant capacity, as measured by ferric reducing-antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and total radical-trapping antioxidant parameter (TRAP). Using Spearman's rank correlation coefficients (CCs), we assessed the validity for dietary NEACs from a 28-day DR and a FFQ, and the reproducibility for them from two FFQs administered at a 1-year interval. Additionally, joint classification and the Bland-Altman method were applied to assess agreement between the two methods. RESULTS: Regarding validation, deattenuated CCs for the energy-adjusted overall dietary NEACs between FFQ and DR for FRAP, ORAC, and TRAP were 0.52, 0.54, and 0.52, respectively, for all subjects. Extreme miscategorization rates by joint classification analysis were 2% for FRAP and ORAC and 1% for TRAP. Regarding reproducibility, CCs between the energy-adjusted dietary NEACs from two FFQs were 0.64 for FRAP and 0.65 for ORAC and TRAP. CONCLUSION: The validity and reproducibility of dietary NEAC of total food from the FFQ were moderate. Estimations of dietary NEAC using FFQ would be useful in studying disease relationships by categorizing habitual dietary NEAC.

Iridoids of Chemotaxonomy Relevance, a New Antirrhinoside Ester and Other Constituents from Kickxia spuria subsp. integrifolia (Brot.) R.Fern.

In this work, the secondary metabolite content of the EtOH extract of Kickxia spuria subsp. integrifolia (Brot.) R.Fern. is reported. Fourteen compounds were isolated and identified by means of column chromatography and NMR and MS instrumental techniques, respectively. Among the identified compounds, the chemotaxonomic markers of the species were evidenced, whereas others were reported for the first time in the genus. Among these, a new antirrhinoside derivative (12) was recognized. The iridoid content showed a molecular pattern very similar to those reported for other taxa comprised in the Antirrhinae tribe of Plantaginaceae, thus providing an additional evidence that supports the current botanical classification of the Kickxia genus. Anyway, most of the recognized components are able to exert important pharmacological properties which might suggest the possible employment of also this species in traditional medicine just like it happens for some other species of the Kickxia genus.

Natural Aromatic Compounds as Scaffolds to Develop Selective G-Quadruplex Ligands: From Previously Reported Berberine Derivatives to New Palmatine Analogues.

In this paper, the selective interactions of synthetic derivatives of two natural compounds, berberine and palmatine, with DNA G-quadruplex structures were reported. In particular, the previous works on this subject concerning berberine were further presented and discussed, whereas the results concerning palmatine are presented here for the first time. In detail, these palmatine derivatives were developed by inserting seven different small peptide basic chains, giving several new compounds that have never been reported before. The preliminary studies of the interactions of these compounds with various G-quadruplex-forming sequences were carried out by means of various structural and biochemical techniques, which showed that the presence of suitable side chains is very useful for improving the interaction of the ligands with G-quadruplex structures. Thus, these new palmatine derivatives might act as potential anticancer drugs.

Dietary antioxidant capacity and all-cause and cause-specific mortality in the E3N/EPIC cohort study.

PURPOSE: The cellular oxidative stress (balance between pro-oxidant and antioxidant) may be a major risk factor for chronic diseases. Antioxidant capacity of human diet can be globally assessed through the dietary non-enzymatic antioxidant capacity (NEAC). Our aim was to investigate the relationship between the NEAC and all-cause and cause-specific mortality, and to test potential interactions with smoking status, a well-known pro-oxidant factor. METHODS: Among the French women of the E3N prospective cohort study initiated in 1990, including 4619 deaths among 1,199,011 persons-years of follow-up. A validated dietary history questionnaire assessed usual food intake; NEAC intake was estimated using a food composition table from two different methods: ferric ion reducing antioxidant power (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hazard ratio (HR) estimates and 95 % confidence intervals (CI) were derived from Cox proportional hazards regression models. RESULTS: In multivariate analyses, FRAP dietary equivalent intake was inversely associated with mortality from all-causes (HR for the fourth vs. the first quartile: HR4 = 0.75, 95 % CI 0.67, 0.83, p trend < 0.0001), cancer, and cardiovascular diseases. Similar results were obtained with TRAP. There was an interaction between NEAC dietary equivalent intake and smoking status for all-cause and cardiovascular disease mortality, but not cancer mortality (respectively, for FRAP, p inter = 0.002; 0.013; 0.113, results were similar with TRAP), and the association was the strongest among current smokers. CONCLUSION: This prospective cohort study highlights the importance of antioxidant consumption for mortality prevention, especially among current smokers.

Chemical Traits of Hemiparasitism in Odontites luteus.

The study of the monoterpene glycosides content of Odontites luteus has shown the presence of a total of fifteen iridoid glucosides. The presence of compounds 1 - 5 and 7 - 10 is perfectly on-line with both the biogenetic pathway for iridoids biosynthesis in Lamiales and the current botanical classification of the species. On the other side, the presence of compounds like agnuside (6), adoxosidic acid (11), monotropein (12), 6,7-dihydromonotropein (13), methyl oleoside (14) and methyl glucooleoside (15) is of high interest because, first of all, they have never been reported before in Lamiales. In second instance, the majority of the last compounds are formally derived from a different biogenetic pathway which involves deoxyloganic acid/loganin and led to the formation of decarboxylated iridoid showing the 8ß-configuration. Furthermore, a second abnormality was found during our study and this regards compounds 14 and 15 which are seco-iriodids and thus not typical for this family. The presence of these unusual compounds, biogenetically not related to species belonging to Lamiales, is a clear evidence of the metabolites transfer from the hosts. In fact, the collection area is also populated by species belonging to Oleaceae and Ericaceae which could be the possible hosts since the biosynthesis of seco-iridoids and or iridoids related to deoxyloganic acid/loganin pathway, with the 8ß-configuration, is well documented in these species.

Terpenoids and More Polar Compounds from the Male Cones of Wollemia nobilis.

The analysis of metabolites contained in the male cones of Wollemia nobilis was investigated for the first time in this study. Several diterpenoids of chemosystematic relevance were recognized for the first time from the genus and/or from the Araucariaceae family, namely isocupressic acid (1), acetyl-isocupressic acid (2), methyl (E)-communate (3) and sandaracopimaric acid (4). All these terpenoids are also endowed with interesting biological activities and may play a primary role in the self defence toward herbivores. The presence of a new norlabdane (norlabda-8(16)-12-dien-14,17-diol) trivially named as wollemol (5) was also recognized. Norditerpenes are scarcely distributed in Plant Kingdom and in particular in Gymnosperms and this aspect was discussed. The structure of 5 was determined by extensive NMR analysis employing mono- and bidimensional experiments. The 7-4‴-dimethoxyagathisflavone (6), a biflavonoid already recognized in Araucariaceae and W. nobilis, was also isolated from male cones together with shikimic acid (7), a biogenetic precursor of polyphenolic compounds, besides carbohydrates such as glucose (8) and saccharose (9), and arginine (10) a quite common amino acid.

Polar Constituents, Essential Oil and Antioxidant Activity of Marsh Woundwort (Stachys palustris L.).

Stachys palustris, well-known as marsh woundwort, is a perennial herb growing in wet environments of Europe. Its tubers, leaves and seeds are eaten raw or cooked. Alike other Stachys species, the plant is also used as a traditional remedy. Despite S. palustris has been consumed for centuries, little is known about its chemical constituents. In this work the main secondary metabolites of S. palustris from Hungary and France have been analysed. From the plant ethanolic extracts, ethanoid glucosides, isoscutellarein derivatives, caffeoyl-quinic acids and iridoids have been isolated and structurally characterized by NMR. The essential oils were analysed by GC/MS and showed (E)-phytol, fatty acids and carbonylic compounds as the most abundant compounds. The radical scavenging capacity of plant ethanolic extracts, as evaluated by the DPPH assay, was noteworthy, with IC50 values of 92.08 - 105.42 µg/ml.

Bioactivity Improvement of Olea europaea Leaf Extract Biotransformed by Wickerhamomyces anomalus Enzymes.

Olive leaves represent a quantitatively significant by-product of agroindustry. They are rich in phenols, mainly oleuropein, which can be hydrolyzed into several bioactive compounds, including hydroxytyrosol. In this study, water extract from olive leaves 'Biancolilla' was analyzed for polyphenol profile, DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity and protective effect on differentiated Caco-2 cells. The efficacy of two enzymatic treatments in promoting the release of bioactive phenols was investigated: a) enzymatic extract from Wickerhamomyces anomalus, characterized by ß-glucosidase and esterase activities; b) commercial ß-glucosidase. Composition and bioactivity of the resulting extracts were compared. The results showed that the yeast-treated extract presented hydroxytyrosol content and DPPH radical scavenging activity comparable to those obtained using commercial ß-glucosidase; however, it was showed the additional presence of hydroxycinnamic acids. In experiments on Caco-2 cells, the leaf extracts promoted the recovery of cell membrane barrier at different minimum effective concentrations. The high specificity of W. anomalus enzymatic extract may represent an effective tool for the release of bioactive phenols from olive by-products.

Dietary total antioxidant capacity and pancreatic cancer risk: an Italian case-control study.

BACKGROUND: Pancreatic cancer is one of the leading causes of cancer mortality. Diet may be associated with pancreatic cancer, but it is unknown whether specific dietary components contribute to its risk. The potential differential role of dietary antioxidants warrants further investigation. METHODS: We analysed data from a case-control study of 326 pancreatic cancer cases and 652 controls conducted between 1991 and 2008 in Northern Italy. Subjects' usual diet was assessed through a validated and reproducible food frequency questionnaire. Using this information and an Italian food composition database, we calculated three indices of dietary total antioxidant capacity (TAC): Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric-reducing antioxidant power (FRAP). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer using multiple logistic regression models conditioned on study centre, sex and age, and adjusted for major known pancreatic cancer risk factors. RESULTS: Significant inverse associations were found for the highest tertile of TAC compared with the lowest tertile for both TEAC and FRAP. The ORs were 0.61 (95% CI 0.39-0.94, P-value for trend 0.03) and 0.63 (95% CI 0.41-0.99, P-value for trend 0.05), respectively. Total radical-trapping antioxidant parameter was inversely, but not significantly, associated with pancreatic cancer risk, with an OR of 0.78 (95% CI 0.49-1.24, P-value for trend 0.27). CONCLUSIONS: Diet high in TAC, as measured by TEAC and FRAP, is inversely associated with pancreatic cancer risk.

Dietary total antioxidant capacity in relation to endometrial cancer risk: a case-control study in Italy.

PURPOSE: To investigate the role of the overall antioxidant activity of diet, we estimated the relation between three dietary indices of total antioxidant capacity (TAC) and endometrial cancer risk METHODS: We analyzed data from an Italian case-control study including 454 women with incident, histologically confirmed endometrial cancer, and 908 frequency-matched controls admitted to the same hospitals as cases for acute non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects' habitual diet. TAC was measured using Italian food composition tables in terms of Ferric-reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and total radical-trapping antioxidant parameter (TRAP). We computed odds ratios (OR) and corresponding 95 % confidence intervals (CIs) using conditional multiple logistic regression models, including terms for recognized endometrial cancer risk factors and total energy intake. RESULTS: TAC was inversely related to endometrial cancer risk with ORs for the highest versus the lowest quartile of 0.69 (95 % CI 0.47-1.00) for FRAP, 0.68 (95 % CI 0.46-0.99) for TEAC, and 0.68 (95 % CI 0.47-0.98) for TRAP. The relations appeared consistent in strata of selected risk factors and decreased when considering TAC without the contribution of coffee. CONCLUSIONS: Our findings suggest a favorable role of a diet high in TAC on endometrial cancer risk, which can be partially driven by coffee consumption.

Secondary Metabolites, Glandular Trichomes and Biological Activity of Sideritis montana L. subsp. montana from Central Italy.

Sideritis montana subsp. montana is a small annual herb occurring in countries bordering the Mediterranean and Balkan regions. The secondary metabolism of this plant has not been fully explored so far. The aim of the present study was to understand the complex mixture of secondary metabolites and the type of secretory structures. The polar constituents were isolated by column chromatography from the ethanolic extract, and their structure was elucidated by NMR and MS. The essential oil was isolated by hydrodistillation and analysed by GC/MS. The plant indumentum was studied by light and scanning electron microscopy. To complete the work, the essential oil antioxidant activity and cytotoxicity on tumor cells were evaluated by DPPH, ABTS, FRAP, and MTT methods. Four different classes of secondary metabolites were isolated, namely flavonoids, caffeoylquinic derivatives, glycosidic hydroquinones and iridoids. The essential oil was mainly characterized by sesquiterpenene hydrocarbons. Peltate and long-capitate hairs were the main sites where terpenes and polar constituents are produced. The secondary metabolites found in S. montana subsp. montana are of chemotaxonomic interest, some of them being typical of the genus Sideritis. The trichomes types observed partially differ from those described in other members of the genus Sideritis. The essential oil showed noteworthy inhibition on tumor cells.

Flavonoids and immune function in human: a systematic review.

Flavonoids, through a modulation of immune function, have been suggested to be involved in the role played by plant foods in disease prevention. We performed a systematic search in the MEDLINE database to review the effect of flavonoid-rich foods and flavonoids supplements on immune function. A total of 58 studies, were identified as suitable: 41 addressed in vivo proinflammatory cytokines and 15 measured ex vivo markers of immune function. According to our findings and on the basis of single food items, the number of studies in humans is limited and, for galenic supplements, only quercetin has been investigated. More evidences are needed to clarify the role of flavonoids as modulator of immune function in humans.