Oxidative Stress Amelioration of Novel Peptides Extracted from Enzymatic Hydrolysates of Chinese Pecan Cake.

Pecan (Carya cathayensis) is an important economic crop, and its hydrolyzed peptides have been evidenced to reduce the effect of oxidative stress due to their antioxidant capacity. Hence, the protocols of ultrafiltration and gel filtration chromatography were established to obtain bioactive peptides from by-products of C. cathayensis (pecan cake). As measured by DPPH/ABTS radical scavenging, the peptides with less molecular weight (MW) possess higher antioxidant capacity. PCPH-III (MW < 3 kDa) presented higher radical scavenging capacity than PCPH-II (3 kDa < MW < 10 kDa) and PCPH-I (MW > 10 kDa) measured by DPPH (IC50: 111.0 µg/ mL) and measured by ABTs (IC50: 402.9 µg/mL). The secondary structure and amino acid composition varied by their MW, in which PCPH-II contained more α-helices (26.71%) and ß-sheets (36.96%), PCPH-III contained higher ratios of ß-turns (36.87%), while the composition of different secondary of PCPH-I was even 25 ± 5.76%. The variation trend of α-helix and random experienced slightly varied from PCPH-I to PCPH-II, while significantly decreased from PCPH-II to PCPH-III. The increasing antioxidant capacity is followed by the content of proline, and PCPH-III had the highest composition (8.03%). With regard to the six peptides identified by LC-MS/MS, two of them (VYGYADK and VLFSNY) showed stronger antioxidant capacity than others. In silico molecular docking demonstrated their combining abilities with a transcription factor Kelch-like ECH-associated protein 1 (Keap1) and speculated that they inhibit oxidative stress through activating the Keap1-Nrf2-ARE pathway. Meanwhile, increased activity of SOD and CAT­antioxidant markers­were found in H2O2-induced cells. The residue of tyrosine was demonstrated to contribute the most antioxidant capacity of VYGYADK and its position affected less. This study provided a novel peptide screening and by-product utilization process that can be applied in natural product developments.

Singular Olive Oils from a Recently Discovered Spanish North-Western Cultivar: An Exhaustive 3-Year Study of Their Chemical Composition and In-Vitro Antidiabetic Potential.

In this work, the quality and physicochemical parameters, phenolic composition, and antidiabetic potential of olive oils obtained from olives belonging to centenarian olive trees of the so-called 'Mansa de Figueiredo' cultivar were evaluated during three consecutive crop seasons (2017-2019). The oils produced during the three crop years were classified as extra virgin based on the quality-related indices, sensory analysis, and the genuineness-related parameters. In addition, LC-ESI-TOF MS was used to get a comprehensive characterisation of the phenolic fraction while LC-ESI-IT MS was applied for quantitation purposes. The content of phenolic compounds (ranging from 1837 to 2434 mg/kg) was significantly affected by the harvest year due to the environmental conditions and ripening index. Furthermore, although significant differences in the inhibitory effects against the α-glucosidase enzyme for the EVOOs extracted throughout the three successive years were detected, all the studied EVOOs exhibited a stronger inhibitor effect than that found for acarbose.

The potential of pumpkin seed oil as a functional food-A comprehensive review of chemical composition, health benefits, and safety.

The growing interest in foods that can be beneficial to human health is bringing into focus some products that have been used locally for centuries but have recently gained worldwide attention. One of these foods is pumpkin seed oil, which has been used in culinary and traditional medicine, but recent data also show its use in the pharmaceutical and cosmetic industries. In addition, some sources refer to it as a potential functional food, mainly because it is obtained from pumpkin seeds, which contain many functional components. However, the production process of the oil may affect the content of these components and consequently the biological activity of the oil. In this review, we have focused on summarizing scientific data that explore the potential of pumpkin seed oil as a functional food ingredient. We provide a comprehensive overview of pumpkin seed oil chemical composition, phytochemical content, biological activity, and safety, as well as the overview of production processes and contemporary use. The main phytochemicals in pumpkin seed oil with health-related properties are polyphenols, phytoestrogens, and fatty acids, but carotenoids, squalene, tocopherols, and minerals may also contribute to health benefits. Most studies have been conducted in vitro and support the claim that pumpkin seed oil has antioxidant and antimicrobial activities. Clinical studies have shown that pumpkin seed oil may be beneficial in the treatment of cardiovascular problems of menopausal women and ailments associated with imbalance of sex hormones.

Prolonged on-tree maturation vs. cold storage of Hass avocado fruit: Changes in metabolites of bioactive interest at edible ripeness.

When the recipient of the product is relatively distant from the production area, it is necessary to use cold storage and controlled humidity to transport the avocado fruits. One of the main advantages of local avocado consumption lies on the possibility of prolonging on-tree maturation; this could foreseeably modify the metabolic profile of the fruit that reaches the consumer. In this work, the effect of prolonged on tree maturation (during different time intervals) on the final composition of avocado fruit (at edible ripeness) was evaluated and compared with the impact of the same periods after prolonged cold storage. The quantitative evolution of nine bioactive metabolites (7 phenolic compounds, pantothenic and abscisic acids) over 40 days (10-days intervals) was studied by using a solid-liquid extraction protocol and a LC-MS methodology. The results were discussed both considering the quantitative evolution of each individual compound and the sum of all of them.

Applicability of an In-Vitro Digestion Model to Assess the Bioaccessibility of Phenolic Compounds from Olive-Related Products.

The Mediterranean diet includes virgin olive oil (VOO) as the main fat and olives as snacks. In addition to providing nutritional and organoleptic properties, VOO and the fruits (olives) contain an extensive number of bioactive compounds, mainly phenolic compounds, which are considered to be powerful antioxidants. Furthermore, olive byproducts, such as olive leaves, olive pomace, and olive mill wastewater, considered also as rich sources of phenolic compounds, are now valorized due to being mainly applied in the pharmaceutical and nutraceutical industries. The digestive system must physically and chemically break down these ingested olive-related products to release their phenolic compounds, which will be further metabolized to be used by the human organism. The first purpose of this review is to provide an overview of the current status of in-vitro static digestion models for olive-related products. In this sense, the in-vitro gastrointestinal digestion methods are widely used with the following aims: (i) to study how phenolic compounds are released from their matrices and to identify structural changes of phenolic compounds after the digestion of olive fruits and oils and (ii) to support the functional value of olive leaves and byproducts generated in the olive industry by assessing their health properties before and after the gastrointestinal process. The second purpose of this review is to survey and discuss all the results available to date.

Evaluation of the status quo of polyphenols analysis: Part II-Analysis methods and food processing effects.

Nowadays due to the concern with the environmental impact of analytical techniques and in order to reduce the ecological footprint there is a tendency to use more efficient and faster procedures that use a smaller amount of organic solvents. Polyphenols have been widely studied in plant-based matrices due to their wide and potent biological properties; however there are no standardized procedures both for sample preparation and analysis of these compounds. The second of a two-part review will carry out a critical review of the extraction procedures and analytical methods applied to polyphenols and their selection criteria over a wide range of factors in relation to commerce-associated, environmental, and economic factors. It is foreseen that in the future the analysis of polyphenols in plant-based matrices includes the use of techniques that allow the simultaneous determination of different subclasses of polyphenols using fast, sophisticated, and automated techniques that allow the minimal consumption of solvents.

Evaluation of the status quo of polyphenols analysis: Part I-phytochemistry, bioactivity, interactions, and industrial uses.

Phytochemicals, especially polyphenols, are gaining more attention from both the scientific community and food, pharmaceutical, and cosmetics industries due to their implications in human health. In this line, lately new applications have emerged, and of great importance is the selection of accurate and reliable analytical methods for better evaluation of the quality of the end-products, which depends on diverse process variables as well as on the matrices and on the physicochemical properties of different polyphenols. The first of a two-part review on polyphenols will address the phytochemistry and biological activities of different classes of polyphenols including flavonoids, lignans and flavanolignans, stilbenoids, tannins, curcuminoids, and coumarins. Moreover, the possible interactions of polyphenols and current and potential industrial applications of polyphenols are discussed.

Dietary phytochemicals in colorectal cancer prevention and treatment: A focus on the molecular mechanisms involved.

Worldwide, colorectal cancer (CRC) remains a major cancer type and leading cause of death. Unfortunately, current medical treatments are not sufficient due to lack of effective therapy, adverse side effects, chemoresistance and disease recurrence. In recent decades, epidemiologic observations have highlighted the association between the ingestion of several phytochemical-enriched foods and nutrients and the lower risk of CRC. According to preclinical studies, dietary phytochemicals exert chemopreventive effects on CRC by regulating different markers and signaling pathways; additionally, the gut microbiota plays a role as vital effector in CRC onset and progression, therefore, any dietary alterations in it may affect CRC occurrence. A high number of studies have displayed a key role of growth factors and their signaling pathways in the pathogenesis of CRC. Indeed, the efficiency of dietary phytochemicals to modulate carcinogenic processes through the alteration of different molecular targets, such as Wnt/ß-catenin, PI3K/Akt/mTOR, MAPK (p38, JNK and Erk1/2), EGFR/Kras/Braf, TGF-ß/Smad2/3, STAT1-STAT3, NF-кB, Nrf2 and cyclin-CDK complexes, has been proven, whereby many of these targets also represent the backbone of modern drug discovery programs. Furthermore, epigenetic analysis showed modified or reversed aberrant epigenetic changes exerted by dietary phytochemicals that led to possible CRC prevention or treatment. Therefore, our aim is to discuss the effects of some common dietary phytochemicals that might be useful in CRC as preventive or therapeutic agents. This review will provide new guidance for research, in order to identify the most studied phytochemicals, their occurrence in foods and to evaluate the therapeutic potential of dietary phytochemicals for the prevention or treatment of CRC by targeting several genes and signaling pathways, as well as epigenetic modifications. In addition, the results obtained by recent investigations aimed at improving the production of these phytochemicals in genetically modified plants have been reported. Overall, clinical data on phytochemicals against CRC are still not sufficient and therefore the preventive impacts of dietary phytochemicals on CRC development deserve further research so as to provide additional insights for human prospective studies.

Industrial-Scale Decontamination Procedure Effects on the Content of Acaricides, Heavy Metals and Antioxidant Capacity of Beeswax.

Beeswax is useful for the beekeeping sector but also for the agro-food, pharmaceutical or cosmetics sectors. Frequently, this bee product is contaminated with pesticides reducing its utility and causing the decline in its market. This study aimed to prove the effectiveness of an industrial-scale decontamination method in removing acaricides from beeswax. Chlorfenvinphos and coumaphos decrease was higher than 90%, whereas tau fluvalinate decrease was only 30%. No changes were observed in the beeswax content of hydrocarbons and monoesters, whereas a decrease in the concentrations of Ca, Fe, Zn, Hg, Mn and P, and an increase in the concentrations of As and Si were found after the decontamination. Filtration reduced total phenolics, flavonoids and the antioxidant capacity of the lipophilic extract. These results demonstrate that the industrial method used was as effective as the method previously tested on a laboratory scale. The study also contributes to a better knowledge and characterization of beeswax, specially related to trace and ultra-trace elements and antioxidant capacity. Moreover, it offers the chance to further develop a method to effectively detect wax adulterations based on the chemical elements profile.

Structure-stability relationship of anthocyanins under cell culture condition.

This work aims to evaluate the structure-stability relationship of anthocyanins in cell culture. An early degradation time (CT10) and half-degradation time (CT50) were used to characterise the stability of 10 of the most common anthocyanins, incubated with DMEM at 37 °C, pH = 7.4, 5% CO2 for different time periods. According to the glycosylation, the glycosylated forms were more stable than the not glycosylated forms. The methylation at 3'' or 5' position at ring B enhanced their stability; contrarily, the hydroxylation at 3' or 5' position at ring B weakened their stability. Glycosylated forms were much more stable in water than in the culture medium. Although not glycosylated forms were also instable in water, their stability was improved compared with culture medium. Together with the cell culture experiments and, in order to avoid artefacts, stability tests of polyphenols should be performed in parallel experiments with DMEM.

Autophagy in Human Health and Disease: Novel Therapeutic Opportunities.

SIGNIFICANCE: In eukaryotes, autophagy represents a highly evolutionary conserved process, through which macromolecules and cytoplasmic material are degraded into lysosomes and recycled for biosynthetic or energetic purposes. Dysfunction of the autophagic process has been associated with the onset and development of many human chronic pathologies, such as cardiovascular, metabolic, and neurodegenerative diseases as well as cancer. Recent Advances: Currently, comprehensive research is being carried out to discover new therapeutic agents that are able to modulate the autophagic process in vivo. Recent evidence has shown that a large number of natural bioactive compounds are involved in the regulation of autophagy by modulating several transcriptional factors and signaling pathways. CRITICAL ISSUES: Critical issues that deserve particular attention are the inadequate understanding of the complex role of autophagy in disease pathogenesis, the limited availability of therapeutic drugs, and the lack of clinical trials. In this context, the effects that natural bioactive compounds exert on autophagic modulation should be clearly highlighted, since they depend on the type and stage of the pathological conditions of diseases. FUTURE DIRECTIONS: Research efforts should now focus on understanding the survival-supporting and death-promoting roles of autophagy, how natural compounds interact exactly with the autophagic targets so as to induce or inhibit autophagy and on the evaluation of their pharmacological effects in a more in-depth and mechanistic way. In addition, clinical studies on autophagy-inducing natural products are strongly encouraged, also to highlight some fundamental aspects, such as the dose, the duration, and the possible synergistic action of these compounds with conventional therapy.

Relevance of functional foods in the Mediterranean diet: the role of olive oil, berries and honey in the prevention of cancer and cardiovascular diseases.

The traditional Mediterranean diet (MedDiet) is a well-known dietary pattern associated with longevity and improvement of life quality as it reduces the risk of the most common chronic pathologies, such as cancer and cardiovascular diseases (CVDs), that represent the principal cause of death worldwide. One of the most characteristic foods of MedDiet is olive oil, a very complex matrix, which constitutes the main source of fats and is used in the preparation of foods, both raw as an ingredient in recipes, and in cooking. Similarly, strawberries and raspberries are tasty and powerful foods which are commonly consumed in the Mediterranean area in fresh and processed forms and have attracted the scientific and consumer attention worldwide for their beneficial properties for human health. Besides olive oil and berries, honey has lately been introduced in the MedDiet thanks to its relevant nutritional, phytochemical and antioxidant profile. It is a sweet substance that has recently been classified as a functional food. The aim of this review is to present and discuss the recent evidence, obtained from in vitro, in vivo and epidemiological studies, on the potential roles exerted by these foods in the prevention and progression of different types of cancer and CVDs.

Beeswax by-Products Efficiently Counteract the Oxidative Damage Induced by an Oxidant Agent in Human Dermal Fibroblasts.

The antioxidant capacity and the phytochemical composition of two by-products from beeswax recycling processes were recently investigated. The aim of the present work was to evaluate the efficacy of one of these by-products, MUD1, against the oxidative stress induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) in human dermal fibroblast (HDF) cells. After a preliminary viability assay, the protective effect of MUD1 was investigated through the measurement of apoptosis level, the reactive oxygen species (ROS) and nitrite (NO2-) production, the level of protein and lipid biomarkers (carbonyl groups, total glutathione and thiobarbituric acid-reactive substance) of oxidative damage, and the measurement of antioxidant enzymes activities (glutatione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase and catalase). The obtained results showed that MUD1 exerted protective effects on HDF, increasing cell viability and counteracted the oxidative stress promoted by AAPH-treatment, and improved mitochondria functionality and wound healing capacities. This work shows the antioxidant effects exerted by beeswax by-products, demonstrating for the first time their potential against oxidative stress in human dermal fibroblast cells; however, further research will be necessary to evaluate their potentiality for human health by more deeply in vitro and in vivo studies.

Phenolic Compounds in Honey and Their Associated Health Benefits: A Review.

Honey is a natural substance appreciated for its therapeutic abilities since ancient times. Its content in flavonoids and phenolic acids plays a key role on human health, thanks to the high antioxidant and anti-inflammatory properties that they exert. Honey possesses antimicrobial capacity and anticancer activity against different types of tumors, acting on different molecular pathways that are involved on cellular proliferation. In addition, an antidiabetic activity has also been highlighted, with the reduction of glucose, fructosamine, and glycosylated hemoglobin serum concentration. Honey exerts also a protective effect in the cardiovascular system, where it mainly prevents the oxidation of low-density lipoproteins, in the nervous system, in the respiratory system against asthma and bacterial infections, and in the gastrointestinal system. A beneficial effect of honey can also be demonstrated in athletes. The purpose of this review is to summarize and update the current information regarding the role of honey in health and diseases.

Protective effects of Manuka honey on LPS-treated RAW 264.7 macrophages. Part 1: Enhancement of cellular viability, regulation of cellular apoptosis and improvement of mitochondrial functionality.

Manuka honey (MH) is a monofloral honey from Australia and New Zealand, well-known for its healthy properties, such as antioxidant, antimicrobial and wound healing capacities. The aim of this work was to assess the phenolic composition and the total antioxidant capacity (TAC) of MH, as well as its effects on cellular viability, proliferation, apoptosis and metabolism in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, highlighting the molecular mechanisms involved. Up to 18 compounds were identified in MH, with gallic acid and quercetin as the major ones; MH showed also remarkable TAC. In addition, MH was able to enhance cellular viability, decrease apoptosis, promote wound healing and attenuate inflammation in a dose-dependent manner, by reducing the expression of caspase 3, p-p38 and p-Erk1/2 proteins, in macrophages stressed with LPS. In addition, it improved mitochondrial respiration and glycolytic activities, stimulating the expression of p-AMPK, SIRT1 and PGC1α, counteracting in this way the deleterious effects of LPS treatment. In conclusion, one of the possible mechanisms by which MH exerts its beneficial effects could be to its capacity to improve cellular viability, promote proliferation and enhance energetic metabolism, by modulating the expression of several proteins involved in apoptosis, inflammation, metabolism and mitochondrial biogenesis.

Protective effects of Manuka honey on LPS-treated RAW 264.7 macrophages. Part 2: Control of oxidative stress induced damage, increase of antioxidant enzyme activities and attenuation of inflammation.

The redox-system is altered by oxidative stress that is initiated by oxidative agents such as lipopolysaccharides (LPS) and reactive oxygen species (ROS), which are strongly involved in chronic inflammation. Even if Manuka honey (MH) is a good source of polyphenol rich antioxidants, its antioxidant and anti-inflammatory effects are still elusive. The aim of the present work was to explore the protective effects of MH against E.coli LPS stimulated oxidative stress and inflammatory condition and the underlying mechanisms on murine RAW 264.7 macrophages. Pre-treatment with MH markedly inhibited LPS induced ROS and nitrite accumulation and increased the protection against cellular biomolecules such as lipids, proteins, and DNA. Stimulation by LPS suppressed both antioxidant enzyme activities and expressions, and Keap1-Nrf2 signaling pathway which was significantly (p < 0.05) increased in the presence of MH. The pro-inflammatory cytokines, such as TNF-α, IL-1ß and IL-6, and other inflammatory mediators (iNOS) were enhanced after LPS treatment, whereas MH suppressed the expression of these inflammatory markers. Moreover, MH also inhibited the expression of TLR4/NF-кB via IкB phosphorylation in LPS-stressed RAW 264.7 macrophages. In conclusion, MH acted as a natural agent for preventing oxidative and inflammatory-related diseases.

Targeting molecular pathways in cancer stem cells by natural bioactive compounds.

Cancer Stem Cells (CSCs) or Tumor-Initiating Cells (TICs) are a small sub-population of cells within the tumor, able to give chemio- and radio-resistance and cause the onset of metastasis and the presence of relapses; for these reasons, they are recently becoming a potential target for anticancer therapy. One of the main characteristics of these cells is the self-renewal through the capability of modulating different molecular signalling pathways, including Wnt/ß-Catenin, Sonic Hedgehog and Notch pathways. Natural bioactive compounds such as resveratrol, epigallocatechin, curcumin, quercetin, ellagic acid, anthocyanins and other compounds and extracts can have a direct or indirect effect on these molecular pathways, decreasing the pathological activities of CSCs. This review aims to report and summarize the in vitro and in vivo studies about the preventive, therapeutic and chemosensitizing effects of these natural bioactive compounds on CSCs deriving from different types of tumors.

Phenolic Compounds Isolated from Olive Oil as Nutraceutical Tools for the Prevention and Management of Cancer and Cardiovascular Diseases.

Non-communicable diseases (NCDs) have become the largest contributor to worldwide morbidity and mortality. Among them, cancer and cardiovascular diseases (CVDs) are responsible for a 47% of worldwide mortality. In general, preventive approaches modifying lifestyle are more cost-effective than treatments after disease onset. In this sense, a healthy diet could help a range of NCDs, such as cancer and CVDs. Traditional Mediterranean Diet (MD) is associated by the low-prevalence of certain types of cancers and CVDs, where olive oil plays an important role. In fact, different epidemiological studies suggest that olive oil consumption prevents some cancers, as well as coronary heart diseases and stroke incidence and mortality. Historically, the beneficial health effects of virgin olive oil (VOO) intake were first attributed to the high concentration of monounsaturated fatty acids. Nowadays, many studies indicate that phenolic compounds contained in olive oil have positive effects on different biomarkers related to health. Among them, phenolic compounds would be partially responsible for health benefits. The present work aims to explore, in studies published during the last five years, the effects of the main phenolic compounds isolated from olive oil on different cancer or CVD aspects, in order to clarify which compounds have more potential to be used as nutraceuticals with preventive or even therapeutic properties.

Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells.

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

Characterization of phenolic extracts from Brava extra virgin olive oils and their cytotoxic effects on MCF-7 breast cancer cells.

The aim of the present work was to evaluate the phenolic profile of the 'Brava' extra virgin olive oil and assess its potential as a "natural adjuvant" in combination with chemotherapy treatment. The total phenol content of the phenolic extracts was 764 mg gallic acid equivalents/kg and the total antioxidant capacity was 2309, 1881 and 2088 µM trolox equivalents/kg determined by Diphenyl-1-picrylhydrazyl free radical method, Ferric Reducing Antioxidant Power and Trolox Equivalent Antioxidant Capacity assay, respectively. Secoiridoids comprised 83% of the total phenolic compounds. The main secoiridoid from oleuropein was the main isomer of oleuropein aglycone (74 mg/kg). The main secoiridoid from ligstroside was the main isomer of ligstroside aglycone (214 mg/kg). These phenolic extracts showed a significant decrease in cell viability on MCF-7 breast cancer cells in a dose and time dependent manner. 48 h-treatments with different concentrations of the extracts induced intracellular ROS generation and cell death.