Dealcoholated red wine has been shown to exert protective effects, reducing the risk of cardiovascular events by improving endothelium-dependent vasodilation and inhibiting platelet aggregation These biological activities have been associated with the polyphenolic components of red wine, suggesting that the pool of phenolic compounds, including flavonoids and anthocyanins, could be responsible for its functional effects. The concept that antioxidant properties of polyphenols could explain the beneficial effects of red wine has been carried forward. Here, we hypothesize a new role of red wine in modulating oxidative stress, leading to the alteration of the antioxidant potential in humans. We previously demonstrated that red wine polyphenols (RWp) protect human erythrocytes from oxidative stress by the activation of an important enzymatic system involved in neutralizing plasma free radicals, namely Plasma Membrane Redox System (PMRS). The present work investigates the underlying mechanism triggered by RWp in the activation of PMRS via the involvement of intracellular GSH. Hence, the increase of GSH intracellular concentration results from the activation of GSH-dependent enzymes, namely glutathione reductase and glucose-6-phosphate dehydrogenase, of about 30% and 50% respectively after 2 min of incubation of human erythrocytes in the presence of RWp (73 ug/ml Gallic Acid Equivalents). Changes in GSH pathway induced by RW were associated with a slight but significant increase (about 15%) of ROS (reactive oxygen species) concentration. We conclude that the pro-oxidant effect of RWp promotes an adaptive stress response in human erythrocytes, which improves their antioxidant defense protecting them from oxidative stress.

Honey has always been used not only as a food/sweetener but also as a medicine since ancient times. The quality and composition depend on many factors, including the botanical origin, the environmental, processing and storage conditions^[1]. The nutritional characteristics and the preventive/therapeutic effect of honey are due to its composition: it contains over 180 different types of compounds including water, carbohydrates, enzymes, amino acids, minerals, vitamins and different phytochemicals^[2] . Among the different effects on health, those most studied in the scientific literature are its antibacterial activity^[3] and the antioxidant capacity^[4]. In recent years the potential anticancer effect of honey, in several tumor cell lines, has also been a reason of study^[5]. Among different types of honey, Manuka, has shown a high anticancer effect, especially in colon cancer cells (LoVo and HCT-116)^[6,7] while it is little known on its effect in cancer stem cells' (CSCs; a rare population of cells within the tumor mass that seem to be responsible for the tumor onset) chemoresistance and the presence of relapse ^[8]. Therefore, the effect of Manuka honey on CSCs-like was evaluated. In general, CSCs-like were enriched from the monolayer population of HCT-116 through the in vitro sphere forming assay^[9]. This honey was able to modify the morphological parameters of the spheroids, reducing the size and volume of the entire culture. The treatment of CSCs-like enriched colonospheres with Manuka honey also led to an intracellular accumulation of ROS and induction of apoptosis. Furthermore, through real-time PCR, down-regulation of ABCG2 gene expression (one of the efflux pumps closely associated with the chemoresistance phenotype) was observed.

References

1. DOI: 10.1016/j.lwt.2017.08.079
2. DOI: 10.3390/molecules23092322
3. DOI: 10.1155/2019/2464507
4. DOI: 10.1016/j.jff.2016.05.008
5. DOI: 10.1016/j.clnu.2018.12.019
6. DOI: 10.1039/c8fo00164b
7. DOI: 10.1039/c8fo00165k
8. DOI: 10.1016/j.phrs.2018.08.006
9. DOI: 10.18632/oncotarget.6261

Black cumin (N. sativa; Ranunculaceae family) is well known for its numerous beneficial biological effects while its seed extracts exhibit anti-diabetic, anti-cancer, immunomodulatory, anti-microbial, anti-inflammatory, anti-hypertensive and antioxidant activities [1,2]. This study aimed to evaluate the phenolic and mineral contents, chemical composition and antioxidant activity of methanolic extracts from dried black cumin seed powder. Also, we have evaluated, after gastrointestinal digestion, the effect of phenolic components and their antioxidant activity by utilising an in vitro gastrointestinal digestion process. Black cumin showed high amounts of total phenolic and flavonoid contents (such as dihydroxybenzoic acid and ferulic acid) via HPLC analysis. Six mineral elements (Ca, Cu, Fe, K, Se, and Zn) were determined by using coupled plasma mass spectrometry. Twenty five (25) fatty acids (13 saturated, 7 unsaturated and 5 unsaturated omega fatty acids) were identified, by gas chromatography, with linoleic acid being the most abundant. In addition, black cumin methanolic extract presented higher antioxidant capacity measured by DPPH, FRAP and TEAC. Finally, dried black cumin powder was evaluated, after gastrointestinal digestion, with results indicating that phenolics, flavonoids and antioxidant capacity to be increased in the gastric fraction (1.81, 1.03 and 2.1-fold respectively) compared with the undigested methanolic extract. Moreover, a higher amount of total phenolic and flavonoid content as well as a higher total antioxidant capacity were found present in the gastric and elimination fraction than in the bio-accessible fraction (that represent the colon availability). Our results demonstrate a significant reduction in the quantity of phenolic (68%) and flavonoid (95.53%) compounds, after gastrointestinal digestion, in the bio-accessible fraction together with a decrease in total antioxidant activity suggesting that phenolic compounds are responsible for the observed antioxidant activity.

References

1. doi=pjbs.2004.441.451
2. doi:1016/S1875-5364(16)30088-7

Aflatoxin B1 (AFB1), the mainly Aspergillus fungi derived mycotoxin, is well known for its carcinogenic effects on liver and frequently occurs in food supplies, leading to fatal consequences in both farm animals and humans. Poultry, one of the most important segment of agro-industry, has demonstrated to be extremely sensitive to AFB1 intake, which results in chickens' low performance, decreased quality of both eggs and meat and a negative economic feedback. Oxidative stress caused by AFB1 plays a crucial role in chickens' kidney damage by generating lipid peroxidation accompanied by a concomitant increase in the antioxidant enzymes involved in ROS metabolism [NADPH oxidase isoform 4 (NOX4) and its regulatory subunit p47-phox]. The aim of the present work was to investigate the benefits of dietary supplementation, in chickens affected by AFB1 mycotoxicosis, using a new Feed additive (FA) containing a mixture of a tri-octahedral Na-smectite with a ligno-cellulose based materialas an antioxidant adjuvant. Exposure of AFB1 treated chickens with the feed additive induced a significant down-regulation of both NOX4 and p47-phox genes expression levels. This trend was confirmed by their protein expression, demonstrating the great potential of the FA to counteract oxidative stress. To conclude, these results could open new perspectives in the way to feed chickens using eco-friendly dietary supplements able to reduce AFB1-induced mycotoxicosis and to ameliorate poultry performances.

The concept that flavonoids, possessing well-known and characterized antioxidant capacity, can fight cancer is deeply rooted in the general population. On the opposite, a current of thought, argued by eminent scientists, attributes to free radical-destroying antioxidants the responsibility to negatively affect cancer incidence and therapy. The field is even more challenging considering that flavonoids possess both antioxidants and pro-oxidant activities and recent publications suggest that their beneficial anticancer effects can be easier explaining evoking the pro-oxidant capacity than the antioxidant one. In the present communication, we will analyze clinical and pre-clinical studies facing these sometimes paradoxical and contradictory concepts proposing that a clear distinction must be done between the use of flavonoids in cancer treatment versus cancer prevention, starting from adequate and specifically selected cellular and animal models. Among the multiple examples, the case of quercetin in chronic lymphocytic leukemia (CLL) will be considered. Quercetin, the most abundant flavonoid present in the diet, is able to modulate several hallmarks of cancer, including resistance to apoptosis. Our studies on this compound allowed us to decipher the biochemical pathway triggered by quercetin leading to demonstrate its capacity to synergistically sensitize several leukemia cell lines and B-cells isolated from CLL patients when associated with different classes of anticancer drugs. We also identified in the protein kinase CK2 the direct and primary target of quercetin, whose inhibition is correlated with the down-regulation of the PI₃K/Akt signaling pathway and the massive apoptosis observed in CLL-derived cells. These data will be commented at the light of the very rapidly cellular uptake of quercetin and its capacity to lower intracellular concentrations of free radical species. Finally, considering the low toxicity of quercetin in normal peripheral blood cells, we will propose the design of clinical trials aimed to demonstrate its efficacy as a potential chemopreventive agent in the early phase of CLL.

Silibinin, a diastereoisomeric mixture extracted from Silybum marianum L, with established anti-prostate cancer activity, has been associated with considerable anti-neoplastic ability, in a variety of human cancer types, through interference with the epigenetic machinery. In prostate carcinoma (PCa), high expression of polycomb repressive complex 1 (PRC1) and 2 (PRC2) members, that belong to polycomb group (PcG) proteins, is associated with transcriptional silencing of tumor suppressor genes through histone modifications and chromatin condensation. Our previous results revealed that silibinin reduced the expression levels of PRC2 complex members (EZH2, EED, SUZ12), an ability accompanied by increased H3K27me3 marks. In the current report, treatment of DU145 and PC3 prostate cancer cells with clinically-achievable concentrations (25-75μg/mL) of silibinin, resulted in reduced protein expression levels of PRC1 complex members (RING1a, RING1b and BMI1), in a dose-dependent manner. Next, human epigenetic chromatin modification enzymes-focused DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) analyses, revealed that silibinin modulated differentially the expression of important enzymes, related with the pathophysiology of the disease, at the epigenetic level. Specifically, significant alterations were observed in the expression profile of enzymes associated with gene expression regulation through modification of chromatin configuration, including family members of: i) histone methyltransferases, ii) histone acetyl-transferases,iii) histone demethylases and iv) histone deacetylases along with enzymes inducing gene silencing (via DNA methylation) and regulation of cell cycle progression. Our results suggest that the anticancer activity of silibinin is partially mediated by the disruption of central processes in chromatin configuration-remodeling and alteration of enzymes of the epigenomic landscape that regulate prostate cancer progression.

Verbena officinalis or vervain is globally used as an herbal medicine and dietary supplement for anti-depressive and anti-convulsive purposes, as well as to treat inflammatory disorders, skin burns, abrasions and gastric problems. In our exploratory research, we investigated the biochemical, antioxidant, and histopathological effects of local V. officinalis infusion in rats previously submitted to chronic physical stress. The animals presented significantly alterations in several organs ratio; namely, epididymis and brain ratios with p=0.003 and p=0,013, respectively. Moreover, tissues like kidney and liver presented relevant histologic alterations due to experimental conditions. Total protein, creatine kinase (CKI), uric acid (URCA), circulating and hepatic alkaline phosphatase (ALP) and Glutathione S-transferases (GSTs), and glucose levels were statistically different between treated and non-treated animals with p<0.05. Altogether, biochemical and haematological results indicated significant impacts in antioxidant, lipidic and protein metabolism. Therefore, physical stress and vervain infusion have significant in vivo effects. Chronic stress effects were not counteracted by vervain consumption (e.g., p=0.5 for hepatic and renal superoxide dismutase (SOD) levels between the different groups). A correlation between histology and the active components in an herbal extract would enable a better evaluation of herbal medicines. Accordingly, further studies of vervain extracts effects are in progress.

Obesity is one of the major problems of the 21^st century worldwide. It is characterized by an expansion of white adipose tissue (WAT) mass resulting from increased adipocytes number and/or size. Excessive accumulation of mature adipocytes is associated with high lipid levels and with a general impairment of catabolic pathways. In this work, we evaluated the effect of a strawberry extract on lipid metabolism and adipogenesis on HepG2 cells and 3T3-L1 adipocytes. The results demonstrated that in HepG2 strawberry extract stimulated the LKB1/AMPK pathway leading to the inactivation of acetyl coenzyme A carboxylase (ACC) and inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the major regulators of fatty acids and cholesterol synthesis, respectively; it also stimulated LDL receptor, sirtuin 1 (Sirt1) and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α). In addition, strawberry extract reduced 3T3-L1 pre-adipocytes differentiation, lipid accumulation and down-regulated the mRNA expression of the adipogenic transcription factors CCAAT/enhancer-binding protein (C/REB-α) and peroxisome proliferation-activated receptor (PPAR-γ). Consistently, it inhibited the expression of fatty acid binding protein (FABP4), ACC and sterol regulatory element-binding protein (SREBP1), by activating AMPK pathway. Strawberry extract also inhibited oxidative stress and inflammation biomarkers, increased antioxidant enzymes activities and mitochondrial functionality. Our results suggest the potential anti-obesity effect of the bioactive components of strawberry.

One of the most studied question in modern history is the particular way of bridging the gap between lifespan and healthspan? Even as average life expectancy has increased, there remains a sizeable gap between life span and health span — the years an individual lives without disease. The second question we must answer is the possibility that our lifespan and/or healthspan is “Programmed” in our genes? Or maybe there are other parameters that contribute to this model? Genome Analysis with “single nucleotide polymorphisms” (SNPs) of exceptionally long-lived people reveal 10-15% complex genetic signatures and very few genes consistently involved. The rest refers to the 3 pillars of metabolic health, the diet, the exercise, and the use of fasting in our everyday plan. Nutrient influence on healthy aging is being extensively studied in humans and in many animal models of aging. Moreover, the latest evidence is showing that regular physical activity can actually slow the aging process on a cellular level and potentially add years to your life. Additionally, intermittent fasting elicits evolutionarily conserved, adaptive cellular responses that are integrated between and within organs in a manner that improves glucose regulation, increases stress resistance, and suppresses inflammation. All these measurements proposed by our research team provides a holistic approach for the evaluation of redox status parameters for several conditions. Therefore, the effect of personalized nutrition on human redox status is evaluated and human health is improved.

Among the various types of dietary agents, isothiocyanates (ITCs) have raised the scientific interest with their unique properties, against disease development, including modulation of the epigenetic machinery. In the context of malignant melanoma, our research efforts have aimed to understand how ITCs induce cell death by interacting with the epigenetic machinery and thus leading to inhibition of tumour growth. For this purpose, we have utilised an experimental in vitro model of human malignant melanoma consisting of normal keratinocytes as well as primary and metastatic melanoma cell lines. In this model, specific ITCs [e.g. Sulforaphane (SFN), Iberin (IBN), Allyl Isothiocyanate (AITC), Benzyl Isothiocyanate (BITC) and Phenethyl Isothiocyanate (PEITC)] were examined for their ability to influence specific histone acetylation and methylation marks, as a potential epigenetic therapeutic strategy against melanoma. Overall, we report that all ITCs inhibited melanoma cell proliferation and influenced acetylation and methylation status of specific lysine residues on H3 and H4 by modulating the expression of various histone acetyl transferases (HATs), histone deacetylases (HDACs) and histone methyl transferases (HMTs), in malignant melanoma cells. Our data highlight novel insights on SFN, IBN, AITC, BITC and PEITC interaction with components of the histone regulatory machinery, to exert their anticancer action in malignant melanoma.