Insights into the Neuroprotective Potential of Epicatechin: Effects against Aß-Induced Toxicity in Caenorhabditis elegans.

Medical therapies to avoid the progression of Alzheimer's disease (AD) are limited to date. Certain diets have been associated with a lower incidence of neurodegenerative diseases. In particular, the regular intake of foods rich in polyphenols, such as epicatechin (EC), could help prevent or mitigate AD progression. This work aims to explore the neuroprotective effects of EC using different transgenic strains of Caenorhabditis elegans, which express human Aß1-42 peptides and contribute to elucidating the mechanisms involved in the effects of EC in AD. The performed assays indicate that this flavan-3-ol was able to reduce the signs of ß-amyloid accumulation in C. elegans, improving motility and chemotaxis and increasing survival in transgenic strain peptide producers compared to nematodes not treated with EC. The neuroprotective effects exhibited by EC in C. elegans could be explained by the modulation of inflammation and stress-associated genes, as well as autophagy, microgliosis, and heat shock signaling pathways, involving the regulation of cpr-5, epg-8, ced-7, ZC239.12, and hsp-16 genes. Overall, the results obtained in this study support the protective effects of epicatechin against Aß-induced toxicity.

Evaluation of the polyphenolic profile of native Ecuadorian stingless bee honeys (Tribe: Meliponini) and their antibiofilm activity on susceptible and multidrug-resistant pathogens: An exploratory analysis.

Biofilms are associated with infections that are resistant to conventional therapies, contributing to the antimicrobial resistance crisis. The need for alternative approaches against biofilms is well-known. Although natural products like stingless bee honeys (tribe: Meliponini) constitute an alternative treatment, much is still unknown. Our main goal was to evaluate the antibiofilm activity of stingless bee honey samples against multidrug-resistant (MDR) pathogens through biomass assays, fluorescence (cell count and viability), and scanning electron (structural composition) microscopy. We analyzed thirty-five honey samples at 15% (v/v) produced by ten different stingless bee species (Cephalotrigona sp., Melipona sp., M. cramptoni, M. fuscopilosa, M. grandis, M. indecisa, M. mimetica, M. nigrifacies, Scaptotrigona problanca, and Tetragonisca angustula) from five provinces of Ecuador (Tungurahua, Pastaza, El Oro, Los Ríos, and Loja) against 24-h biofilms of Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, and Candida tropicalis. The present honey set belonged to our previous study, where the samples were collected in 2018-2019 and their physicochemical parameters, chemical composition, mineral elements, and minimal inhibitory concentration (MIC) were screened. However, the polyphenolic profile and their antibiofilm activity on susceptible and multidrug-resistant pathogens were still unknown. According to polyphenolic profile of the honey samples, significant differences were observed according to their geographical origin in terms of the qualitative profiles. The five best honey samples (OR24.1, LR34, LO40, LO48, and LO53) belonging to S. problanca, Melipona sp., and M. indecisa were selected for further analysis due to their high biomass reduction values, identification of the stingless bee specimens, and previously reported physicochemical parameters. This subset of honey samples showed a range of 63-80% biofilm inhibition through biomass assays. Fluorescence microscopy (FM) analysis evidenced statistical log reduction in the cell count of honey-treated samples in all pathogens (P <0.05), except for S. aureus ATCC 25923. Concerning cell viability, C. tropicalis, K. pneumoniae ATCC 33495, and K. pneumoniae KPC significantly decreased (P <0.01) by 21.67, 25.69, and 45.62%, respectively. Finally, scanning electron microscopy (SEM) analysis demonstrated structural biofilm disruption through cell morphological parameters (such as area, size, and form). In relation to their polyphenolic profile, medioresinol was only found in the honey of Loja, while scopoletin, kaempferol, and quercetin were only identified in honey of Los Rios, and dihydrocaffeic and dihydroxyphenylacetic acids were only detected in honey of El Oro. All the five honey samples showed dihydrocoumaroylhexose, luteolin, and kaempferol rutinoside. To the authors' best knowledge, this is the first study to analyze stingless bees honey-treated biofilms of susceptible and/or MDR strains of S. aureus, K. pneumoniae, and Candida species.

Biochemical Profile and Antioxidant Properties of Propolis from Northern Spain.

The antioxidant, anti-inflammatory, and antimicrobial characteristics of propolis, a bioactive compound collected from hives, have prompted its use in the food sector in recent times. This study investigated the physicochemical characteristics, phenolic profile, and antioxidant capacity of 31 propolis extracts collected from Northern Spain. The physicochemical composition (resins, waxes, ashes mineral content, and heavy metals) was within the allowable regulatory limits. The analysis of bioactive compounds enabled the identification of 51 constituents: flavonoids (apigenin, catechin, chrysin, quercetin, and pinocembrin) and phenolic acids (caffeic, ferulic, and coumaric). The mean value of total polyphenols was 42.72 ± 13.19 Pinocembrin-Galangin Equivalents/100 g, whereas a range between 1.64 ± 0.04 and 4.95 ± 0.36 Quercetin Equivalents (QE) g/100 g was found for total flavonoids content. The determination of bioactivities revealed significant antioxidant capacity using DPPH (1114.28 ± 10.39 µM Trolox Equivalents and 3487.61 ± 318.66 µM Vitamin C Equivalents). Resin content in propolis samples was positively and significantly correlated with both polyphenols (rho = 0.365; p = 0.043) and flavonoid composition (rho = 0.615; p = 0.000) as well as the antioxidant capacity TEAC DPPH (rho = 0.415; p = 0.020). A multiple regression analysis modeled the correlation between resin composition, flavonoids, and TEAC DPPH values, yielding a significant regression equation (R2 = 0.618; F (2,28) = 22.629; p < 0.000; d = 2.299). Therefore, evaluating physicochemical parameters and biological activities provides a promising framework for predicting propolis' quality and antioxidant properties, thus suggesting its potential as a functional and bioactive compound for the food industry.

The effects of polyphenols against oxidative stress in Caenorhabditis elegans are determined by coexisting bacteria.

Introduction: Increasing evidence supports the role of gut microbiota in many aspects of human health, including immune, metabolic and neurobehavioral traits. Several studies have focused on how different components of the diet, such as polyphenols, can modulate the composition and function of the gut microbiota leading to health benefits. Methods: The effects on the resistance against thermally induced oxidative stress of C. elegans grown in the presence of flavonoids (quercetin or epicatechin) and fed different probiotic strains, namely Lactobacillus plantarum CLC17, Bifidobacterium longum NCIMB 8809 and Enterococcus faecium CECT 410, were explored. Results: Feeding C. elegans with the assayed bacteria in the absence of flavonoids did not significantly affect body size and fertility of the worms neither improve their resistance against oxidative stress compared to E. coli controls. However, increased resistance to stress was found when C. elegans was cultivated in the presence of both L. plantarum and flavonoids, but not with B. longum or E. faecium. An exploratory study revealed the presence of glycosylated and sulfated metabolites together with the aglycone in worms treated with quercetin and fed any of the different assayed LAB strains. However, in the assays with epicatechin a differential metabolite, tentatively identified as 5-(4'-hydroxyphenyl)-γ-valerolactone 3'-O-glucoside, was detected in the worms fed L. plantarum but not with the other bacteria. Conclusion: The obtained results indicated that the interactions bacteria/polyphenol play a key role in the effects produced in C. elegans regarding resistance against oxidative stress, although those effects cannot be only explained by the ability of bacteria to metabolize polyphenols, but other mechanisms should also be involved.

Influence of Altitudes and Development Stages on the Chemical Composition, Antioxidant, and Antimicrobial Capacity of the Wild Andean Blueberry (Vaccinium floribundum Kunth).

The chemical composition and biological capacities of berries depend on environmental parameters, maturity, and location. The Andean blueberry (Vaccinium floribundum Kunth), also known as mortiño, presents a unique combination of several phytochemicals, which play a synergistic role in its characterization as a functional food. We aimed to expose the possible variations that exist in the profile of the phenolic compounds as well as the antioxidant and antimicrobial capacity of the wild Andean blueberry with respect to three ripeness stages and two different altitudes. We found that polyphenols are the predominant compounds in the berry during the early ripeness stage and are the main bioactive compounds that give rise to the antioxidant capacity and inhibition effect on the growth of gram-positive and gram-negative bacteria. Moreover, the accumulation of ascorbic acid, free amino acids, and anthocyanins increases as the ripening process progresses, and they were the main bioactive compounds in the ripe berry. The latter compounds influence the production of the typical bluish or reddish coloration of ripe blueberries. In addition, it was determined that environmental conditions at high altitudes could have a positive influence in all cases. Overall, our data provide evidence regarding the high functional value of the wild Andean blueberry.

Disclosing the Antioxidant and Neuroprotective Activity of an Anthocyanin-Rich Extract from Sweet Cherry (Prunus avium L.) Using In Vitro and In Vivo Models.

In this study, an autochthonous variety of sweet cherry (Prunus avium L.), namely "Moretta di Vignola", was processed to prepare extracts rich in polyphenols, which were characterized by high-performance liquid chromatography (HPLC) separation coupled to UV/DAD and ESI-MSn analysis. Then, a sweet cherry anthocyanin-rich extract (ACE) was prepared, fully characterized and tested for its activity against Parkinson's disease (PD) in cellular (BV2 microglia and SH-SY5Y neuroblastoma) and in Drosophila melanogaster rotenone (ROT)-induced model. The extract was also evaluated for its antioxidant activity on Caenorhabditis elegans by assessing nematode resistance to thermal stress. In both cell lines, ACE reduced ROT-induced cell death and it decreased, alone, cellular reactive oxygen species (ROS) content while reinstating control-like ROS values after ROT-induced ROS rise, albeit at different concentrations of both compounds. Moreover, ACE mitigated SH-SY5Y cell cytotoxicity in a non-contact co-culture assay with cell-free supernatants from ROT-treated BV-2 cells. ACE, at 50 µg/mL, ameliorated ROT (250 µM)-provoked spontaneous (24 h duration) and induced (after 3 and 7 days) locomotor activity impairment in D. melanogaster and it also increased survival and counteracted the decrease in fly lifespan registered after exposure to the ROT. Moreover, heads from flies treated with ACE showed a non-significant decrease in ROS levels, while those exposed to ROT markedly increased ROS levels if compared to controls. ACE + ROT significantly placed the ROS content to intermediate values between those of controls and ROT alone. Finally, ACE at 25 µg/mL produced a significant increase in the survival rate of nematodes submitted to thermal stress (35 °C, 6-8 h), at the 2nd and 9th day of adulthood. All in all, ACE from Moretta cherries can be an attractive candidate to formulate a nutraceutical product to be used for the prevention of oxidative stress-induced disorders and related neurodegenerative diseases.

Protective Effect of Quercetin 3-O-Glucuronide against Cisplatin Cytotoxicity in Renal Tubular Cells.

Quercetin, a flavonoid with promising therapeutic potential, has been shown to protect from cisplatin nephrotoxicity in rats following intraperitoneal injection, but its low bioavailability curtails its prospective clinical utility in oral therapy. We recently developed a micellar formulation (P-quercetin) with enhanced solubility and bioavailability, and identical nephroprotective properties. As a first aim, we herein evaluated the oral treatment with P-quercetin in rats, which displayed no nephroprotection. In order to unravel this discrepancy, quercetin and its main metabolites were measured by HPLC in the blood and urine after intraperitoneal and oral administrations. Whilst quercetin was absorbed similarly, the profile of its metabolites was different, which led us to hypothesize that nephroprotection might be exerted in vivo by a metabolic derivate. Consequently, we then aimed to evaluate the cytoprotective capacity of quercetin and its main metabolites (quercetin 3-O-glucoside, rutin, tamarixetin, isorhamnetin and quercetin 3-O-glucuronide) against cisplatin toxicity, in HK-2 and NRK-52E tubular cell lines. Cells were incubated for 6 h with quercetin, its metabolites or vehicle (pretreatment), and subsequently 18 h in cotreatment with 10-300 µM cisplatin. Immediately after treatment, cell cultures were subject to the MTT technique as an index of cytotoxicity and photographed under light microscopy for phenotypic assessment. Quercetin afforded no direct cytoprotection and quercetin-3-O-glucuronide was the only metabolite partially preventing the effect of cisplatin in cultured tubule cells. Our results identify a metabolic derivative of quercetin contributing to its nephroprotection and prompt to further explore exogenous quercetin-3-O-glucuronide in the prophylaxis of tubular nephrotoxicity.

Wine, Polyphenols, and Mediterranean Diets. What Else Is There to Say?

A considerable amount of literature has been published claiming the cardiovascular benefits of moderate (red) wine drinking, which has been considered a distinguishing trait of the Mediterranean diet. Indeed, red wine contains relevant amounts of polyphenols, for which evidence of their biological activity and positive health effects are abundant; however, it is also well-known that alcohol, even at a low level of intake, may have severe consequences for health. Among others, it is directly related to a number of non-communicable diseases, like liver cirrhosis or diverse types of cancer. The IARC classifies alcohol as a Group 1 carcinogen, causally associated with the development of cancers of the upper digestive tract and liver, and, with sufficient evidence, can be positively associated with colorectum and female breast cancer. In these circumstances, it is tricky, if not irresponsible, to spread any message on the benefits of moderate wine drinking, about which no actual consensus exists. It should be further considered that other hallmarks of the Mediterranean diet are the richness in virgin olive oil, fruits, grains, and vegetables, which are also good sources of polyphenols and other phytochemicals, and lack the risks of wine. All of these aspects are reviewed in this article.

Bioactive compounds, phenolic profile, antioxidant capacity and effectiveness against lipid peroxidation of cell membranes of Mauritia flexuosa L. fruit extracts from three biomes in the Ecuadorian Amazon.

The bioactive compounds, total antioxidant capacity and protective effect against lipid oxidative damage of red blood cell (RBC) membranes of Mauritia flexuosa L. extracts from three altitude levels (low, middle and high zones) were analyzed. The identification of the main polyphenols in the fruit was performed using High Performance Liquid Chromatography/Electrospray Ionization Tandem Mass Spectrometry analysis, while High-Performance Liquid Chromatography - Diode Array Detector was applied for the vitamin C and carotenoid analysis. The ability of the extracts (methanolic, free polyphenols and bound polyphenols) to protect RBC membranes against oxidative destruction was assessed utilizing the thiobarbituric acid reactive substance assay (TBARS) assay. Among the 14 phenolic compounds identified, quercetin glycosides were the most predominant ones. The fruit from the middle altitude zone showed higher vitamin C and lutein contents than those from the low and high areas, whilst higher values of ß-Carotene were obtained in M. flexuosa L. from the low zone. The contents of flavonoids and total polyphenols were lower in fruit from the low zone, whilst the fruit from the middle zone had the highest values. Similar results were observed in the results of the antioxidant capacity assays. However, a significant difference was not found in the protective effect of the extracts from the three altitude zones against lipid peroxidation in RBC membranes.

Caernohabditis elegans as a Model Organism to Evaluate the Antioxidant Effects of Phytochemicals.

The nematode Caernohabditis elegans was introduced as a model organism in biological research by Sydney Brenner in the 1970s. Since then, it has been increasingly used for investigating processes such as ageing, oxidative stress, neurodegeneration, or inflammation, for which there is a high degree of homology between C. elegans and human pathways, so that the worm offers promising possibilities to study mechanisms of action and effects of phytochemicals of foods and plants. In this paper, the genes and pathways regulating oxidative stress in C. elegans are discussed, as well as the methodological approaches used for their evaluation in the worm. In particular, the following aspects are reviewed: the use of stress assays, determination of chemical and biochemical markers (e.g., ROS, carbonylated proteins, lipid peroxides or altered DNA), influence on gene expression and the employment of mutant worm strains, either carrying loss-of-function mutations or fluorescent reporters, such as the GFP.

Protective effect of the medicinal herb infusion "horchata" against oxidative damage in cigarette smokers: An ex vivo study.

Cigarette smoking has been associated with an increase in oxidative stress (OS) and is considered a predisposing factor to chronic noncommunicable diseases, whilst dietary antioxidants has been proposed as an alternative to cope with this oxidative stress. In this study, 20 smokers and 20 non-smokers were studied with the aim of determining their antioxidant status, as well as the ability of an infusion of 23 medicinal plants, to counteract the damage caused by OS. The plasma, red blood cells (RBCs) and polymorphonuclear cells (PBMCs) of both groups were incubated or not with the horchata infusion extract and then the OS markers, genotoxicity, nanostructure of RBCs membrane and genes related to oxidative responses and cellular functionality were evaluated. Up to 33 different compounds, mainly quercetin glycosides, were identified in the extract. A significant deterioration in the antioxidant status in smokers compared to non-smokers was found. The horchata infusion extract improved the nanostructure of RBCs and DNA damage, as well as the activity of the endogenous antioxidant enzymes and markers of oxidative damage to lipid, and proteins in plasma, RBCs and PBMCs in both groups, whilst no significant changes were found in the expression of different genes related to OS response.

Current and future experimental approaches in the study of grape and wine polyphenols interacting gut microbiota.

Interactions between polyphenols and gut microbiota are indeed a major issue of current interest in food science research. Knowledge in this subject is progressing as the experimental procedures and analysis techniques do. The aim of this article is to critically review the more leading-edge approaches that have been applied so far in the study of the interactions between grape/wine polyphenols and gut microbiota. This is the case of in vitro dynamic gastrointestinal simulation models that try to mitigate the limitations of simple static models (batch culture fermentations). More complex approaches include the experimentation with animals (mice, rats, pigs, lambs and chicks) and nutritional intervention studies in humans. Main advantages and limitations as well as the most relevant findings achieved by each approach in the study of how grape/wine polyphenols can modulate the composition and/or functionality of gut microbiota, are detailed. Also, common findings obtained by the three approaches (in vitro, animal models and human nutritional interventions) such as the fact that the Firmicutes/Bacteroidetes ratio tends to decrease after the feed/intake/consumption of grape/wine polyphenols are highlighted. Additionally, a nematode (Caenorhabditis elegans) model, previously used for investigating the mechanisms of processes such as aging, neurodegeneration, oxidative stress and inflammation, is presented as an emerging approach for the study of polyphenols interacting gut microbiota. © 2020 Society of Chemical Industry.

Plant phenolics as functional food ingredients.

Phenolic compounds have attracted much attention in recent times as their dietary intake has been associated with the prevention of some chronic and degenerative diseases that constitute major causes of death and incapacity in developed countries, such as cardiovascular diseases, type II diabetes, some types of cancers or neurodegenerative disorders like Alzheimer's and Parkinson's diseases. Nowadays it is considered that these compounds contribute, at least in part, for the protective effects of fruit and vegetable-rich diets, so that the study of their role in human nutrition has become a central issue in food research. This chapter reviews the current knowledge on the phenolic compounds as food components, namely their occurrence in the diet, bioavailability and metabolism, biological activities and mechanisms of action. Besides, the approaches for their extraction from plant matrices and technological improvements regarding their preparation, stability and bioavailability in order to be used as functional food ingredients are also reviewed, as well as their legal situation regarding the possibility of making "health claims" based on their presence in food and beverages.

Anti-inflammatory effect of the medicinal herbal mixture infusion, Horchata, from southern Ecuador against LPS-induced cytotoxic damage in RAW 264.7 macrophages.

The phytochemical composition and the antioxidant and anti-inflammatory activities of a mixture of 23 plants, named Horchata, traditionally consumed in Ecuador, have been evaluated. The study was carried out using the hydroalcoholic extract (HHext) and infusion (IHext) of the horchata plant mixture. It was verified that thermal treatment affected the contents of vitamin C and carotenoids, but hardly those of polyphenols, which would be the main bioactive compounds in the infusion, the common form of preparation of horchata for consumption. Among phenolic compounds, caffeoylquinic acids, flavones and flavonols (mostly quercetin glycosides) were prominent. Both HHext and IHext extracts managed to protect RAW 264.7 macrophages against LPS-induced cytotoxic damage, increasing the levels of endogenous antioxidant enzymes and modulating the production of pro-inflammatory and anti-inflammatory cytokines. Greater protective effects were obtained for HHext compared to IHext, which was in agreement with its higher content of phenolic compounds favoured by a more efficient extraction in the hydroalcoholic medium. Nonetheless, the infusion still maintained a significant antioxidant and anti-inflammatory activity, which would support the protective effects on health traditionally attributed to its consumption by the population.

Antioxidant Characterization and Biological Effects of Grape Pomace Extracts Supplementation in Caenorhabditis elegans.

The aim of this work was to evaluate the biological activity of four grape pomace (GP) extracts that are rich in polyphenols using C. elegans as an in vivo model. Different concentrations of the GP extracts were assessed for their effects on the resistance of C. elegans against thermally induced oxidative stress, accumulation of reactive oxygen species (ROS), and lifespan. The cultivation of C. elegans with relatively low concentrations of GP extracts increased their resistance against thermal stress and prolonged their lifespan, while high levels displayed detrimental effects. In the studied extracts, maximum protection was observed for levels of polyphenols around 7 to 9 µg gallic acid equivalents per cultivation plate. The obtained results suggested that small changes in the ROS levels could have beneficial effects, although further studies are required to fully understand the impact of the extracts and assayed doses on ROS levels to explain the mechanism that is involved in the observed effects.

Preparation and Characterization of Protocatechuic Acid Sulfates.

Protocatechuic acid (3,4-dihydroxybenzoic acid; PCA) is a phenolic acid present in plants as a secondary metabolite and is also produced in the human organism as a metabolite from the degradation of polyphenols by the intestinal microbiota, particularly of flavonoids. However, PCA, like most polyphenols, is biotransformed in the human body to different conjugates as sulfates, which are found circulating in blood and could be involved in the bioactivity of the original compound. This paper describes a simple process for the preparation of PCA monosulfates with satisfactory yields. Two compounds were obtained that were identified as PCA-3-sulfate and PCA-4-sulfate by mass spectrometry and ¹H and 13C nuclear magnetic resonance using one- and two-dimensional techniques (heteronuclear single-quantum coherence and heteronuclear multiple-bond correlation). Differential MS fragmentation behavior and UV spectra were observed for each compound, which could be used for their identification in samples of unknown composition. The described procedure can be used for the preparation of these polyphenol metabolites in view of their use in in vivo and in vitro studies, as well as standards for their analysis in biological fluids, to contribute to the elucidation of biological effects of dietary polyphenols.

The Mechanisms Behind the Biological Activity of Flavonoids.

Flavonoids are phenolic compounds widely distributed in the human diet. Their intake has been associated with a decreased risk of different diseases such as cancer, immune dysfunction or coronary heart disease. However, the knowledge about the mechanisms behind their in vivo activity is limited and still under discussion. For years, their bioactivity was associated with the direct antioxidant and radical scavenging properties of phenolic compounds, but nowadays this assumption is unlikely to explain their putative health effects, or at least to be the only explanation for them. New hypotheses about possible mechanisms have been postulated, including the influence of the interaction of polyphenols and gut microbiota and also the possibility that flavonoids or their metabolites could modify gene expression or act as potential modulators of intracellular signaling cascades. This paper reviews all these topics, from the classical view as antioxidants in the context of the Oxidative Stress theory to the most recent tendencies related with the modulation of redox signaling pathways, modification of gene expression or interactions with the intestinal microbiota. The use of C. elegans as a model organism for the study of the molecular mechanisms involved in biological activity of flavonoids is also discussed.

Revalorization of wild Asparagus stipularis Forssk. as a traditional vegetable with nutritional and functional properties.

The nutritional values and phytochemical composition of young shoots of wild Asparagus stipularis Forssk. from Tunisia were determined in this study. The antioxidant (tested by four different in vitro assays) and antiproliferative properties (against human tumour cell lines) of aqueous and hydroalcoholic extracts of the young shoots were also investigated. The obtained results indicated that the young shoots are a potential source of valuable nutrients and dietary fiber, and their hydroalcoholic extract showed marked antioxidant and antiproliferative activities in all tested assays. The major phenolic compound, characterized by using a high-performance liquid chromatograph coupled with diode-array and mass spectrometer detectors, in both extracts was diferuloyl glycerol. Our results reinforce the interest in recovering the traditional culinary uses of this wild plant, with potential functional properties, which can be included in the modern diet as an alternative to the variety of vegetables normally used.

The protective effect of acerola (Malpighia emarginata) against oxidative damage in human dermal fibroblasts through the improvement of antioxidant enzyme activity and mitochondrial functionality.

Acerola fruits (Malpighia emarginata DC.) from the central region of Cuba were analyzed to determine their chemical composition and protective capacity against oxidative damage using an in vitro human dermal fibroblast (HDFa) model. The chemical composition analyses showed a high content of vitamin C, total polyphenols, ß-carotene and folates in the acerola fruit. From the HPLC-DAD/ESI-MSn analyses, two anthocyanins (cyanidin 3-O-rhamnoside and pelargonidin 3-O-rhamnoside), three hydroxycinnamoyl derivatives (caffeoyl hexoside, dihydrocaffeoylquinic acid and coumaroyl hexoside) and fifteen flavonols (mostly glycosylated forms of quercetin and kaempferol) were detected. HDFa were pre-incubated with an acerola crude extract (ACExt) and subsequently subjected to oxidative stress induced by AAPH. Apoptosis, intracellular ROS and the biomarkers of lipid and protein oxidation significantly increased after inducing stress, while the activities of the antioxidant enzyme catalase and superoxide dismutase and mitochondrial functionality were markedly affected. However, ACExt was able to protect against oxidative damage through decreasing apoptosis, intracellular ROS levels and lipid and protein damage, besides improving antioxidant enzyme activities and mitochondrial functionality. The obtained results support acerola fruits as relevant sources of functional compounds with promising effects on human health.

Broad-range potential of Asphodelus microcarpus leaves extract for drug development.

BACKGROUND: Many plants have been used in traditional medicine for their antibacterial, antifungal, antiprotozoal, antiviral, antidiarrhoeal, analgesic, antimalarial, antioxidant, anti-inflammatory and anticancer activities. In order to find novel antimicrobial and antiviral agents, the aim of the present study was the evaluation of the antibacterial and antibiofilm susceptibility of Asphodelus microcarpus leaves extract. Moreover, the antiviral activity and the phytochemical composition of the active extract were also determined. METHODS: Antimicrobial and antibiofilm activities of leaves ethanol extract of A. microcarpus were evaluated on 13 different microbial strains. We selected three different sets of microorganisms: (i) Gram-positive bacteria, (ii) Gram-negative bacteria and (iii) yeasts. The potential antiviral activity of A. microcarpus leaves ethanol extract was evaluated with a luciferase reporter gene assay in which the dsRNA-dependent RIG-I-mediated IFN-ß activation was inducted or inhibited by the Ebola virus VP35 protein. HPLC-DAD-MS was used to identify phenolic profile of the active extract. RESULTS: A. microcarpus leaves extract showed a potent inhibitory activity on Gram-positive bacteria while only a reduced inhibition was observed on Gram-negative bacteria. No activity was detected against Yeasts. The extract also showed an interesting antibiofilm motif on various bacterial strains (E. coli, S. aureus, S. haemolyticus and B. clausii). Moreover, this extract significantly affected the Ebola virus VP35 inhibition of the viral RNA (vRNA) induced IFN response. CONCLUSIONS: The overall results provide supportive data on the use of A. microcarpus as antimicrobial agent and a potential source of anti-viral natural products. Data collected set the bases for further studies for the identification of single active components and the development of new pharmaceuticals.