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Introduction: Dimethyl sulfoxide (DMSO) is widely used as a diluent and/or solvent for pharmacological compounds. Furthermore, DMSO crosses the blood-brain barrier acting on the nervous system. The natural compounds phenylamides and lignanamides (LnHS) have protective effects on neuronal health, being promising neuroprotective candidates. In this scenario, we evaluated the impact of DMSO and/or LnHS on SH-SY5Y and U-87 cells, taken as in vitro model of neurons and glia. Methods: Cells were treated with DMSO and/or LnHS at different doses and proliferation (MTT and trypan blue counting, colony forming ability, autophagy, oxidative stress (NO, ROS determination) and inflammatory (IL8, IL6, TNFα mRNA expression) response was evaluated. Results: We found that DMSO reduces both neuronal and glial cell viability, while LnHS does not affect viability of SH-SY5Y cells but reduces that of U-87 cells. Therefore, we focused on SHSY5Y cells and investigated whether LnHS could counteract DMSO toxicity. LnHS partially attenuates the inhibitory effects of DMSO on cell viability and restores the colony-forming ability of SH-SY5Y cells exposed to DMSO. Furthermore, we found that co-administration of LnHS modulates the expression of SIRT3 and SOD2 enzymes, reduces nitrite release and ROS generation increasing IL-8 levels. Interestingly, co-administration of LnHS counteracts the DMSO-induced production of IL-6, while no modification in TNF-α was found. Discussion: Our study indicates LnHS as a potential feasible compound to support neuronal health as it counteracts DMSO induced cytotoxic effects by improving SH-SY5Y cells survival. Further studies are needed to clarify the molecular mechanisms underlying the LnHS biological activities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mallardo, Pacifico, Piccolella, Di Meo, Rizzo, Daniele and Nigro.)

Walnut processing generates considerable quantities of by-products that could be reprocessed into value-added products that have food and non-food applications. In this context, the aim of this study is to characterize the 'Sorrento' and 'Tulare' walnut cultivars using the UPOV guidelines and analyze the chemical composition and antioxidant activity of their shells. Insight into the chemical composition of the different granulometric fractions of walnut shell, obtained by sieving, was obtained following ultrasound-assisted extraction by Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS). The total phenolic, flavonoid, and tannin content and antiradical capacity, obtained by DPPH and ABTS assays, and the Fe(III) reducing power of the extracts were also evaluated. The UHPLC-HRMS analysis indicated the presence of thirty-two compounds ascribable to four major classes of specialized metabolites. Furthermore, the extraction efficiency of gallic acid, ellagic acid derivatives, as well as glansreginin A, increased with the decrease in shell matrix particle size in contrast to chlorogenic acids and flavonoid glycosides. This is the first study to highlight new knowledge on the chemical composition of walnut shells. The results obtained demonstrate the feasibility of recovering valuable bioactive components from agro-waste that may be further valorized.

In a framework aimed at the recovery and enhancement of medicinal plants endemic to the territory of the Cilento and Vallo di Diano National Park, Lavandula austroapennina N.G. Passal., Tundis and Upson has aroused interest. An insight into the chemical composition of the corolla, calyx, leaf, stem, and root organs was carried out following ultrasound-assisted maceration in n -hexane. The obtained lipophilic extracts were explored using ultra-high-performance chromatography coupled to high-resolution mass spectrometry (UHPLC-ESI-QqTOF-MS/MS). The extracts from the different organs varied in their relative content of fatty acids, ursanes, and oleanane-type triterpenes. In particular, the oleanolic acid content appeared to increase in the order of corolla < leaf < stem. An MTT assay was performed to verify the possible cytotoxicity of the organ extracts of L. austroapennina at a concentration ranging from 12.5 to 400 µg/mL on the Vero CCL-81 cell line. Antiviral activity against herpes simplex virus type 1 (HSV-1), alpha human coronavirus 229E (HCoV-229E), and poliovirus type 1 (PV-1) was evaluated via a plaque reduction assay in the same cellular model. All the extracts did not show cytotoxic effects after 2 and 24 h exposure times, and the antiviral efficacy was particularly important for the stem extract, capable of completely inhibiting the tested viruses at low doses. The antiviral activity in a non-enveloped virus PV-1 allowed the assertion that the extracts from the organs of L. austroapennina , and especially the stem extract, interfered directly with the viral envelope. This study underlines how much knowledge of a territory's medicinal plant heritage is a harbinger of promising discoveries in the health field.

In recent years, as part of sustainable development policies, the revaluation of end-of-life products has become more and more widespread. In terms of sustainability, in a scenario of circular economy food sustainability aims, inter alia, at making an effective re-use of natural resources as a starting point for the obtainment of high added-value products. With the aim of promoting the valorization of the wine sector wastes, the present study took into account the leaves of Vitis vinifera L. cv. Aglianico from the Campania Region (Italy). The use of deep eutectic solvents as a greener alternative to the most common organic solvents, joint to ultrasound-assisted maceration, and LC-MS tools, allowed us to define for the first time a six-month quantitative variation of flavonol derivatives, and in particular of quercetin 3- O -glucuronide, based on the collection time and the leaf height on the grapevine. Results underlined that the influence of abiotic factors, such as exposure to sunlight, which is pivotal in the biosynthesis of such compounds, should be strictly considered for their full recovery.

In the last decades, the interest in bioactive compounds derived from natural sources including bacteria, fungi, plants, and algae has significantly increased. It is well-known that aquatic or terrestrial organisms can produce, in special conditions, secondary metabolites with a wide range of biological properties, such as anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. In this study, we focused on the extremophilic microalga Galdieria sulphuraria as a possible producer of bioactive compounds with antiviral activity. The algal culture was subjected to organic extraction with acetone. The cytotoxicity effect of the extract was evaluated by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The antiviral activity was assessed through a plaque assay against herpesviruses and coronaviruses as enveloped viruses and poliovirus as a naked one. The monolayer was treated with different concentrations of extract, ranging from 1 µg/mL to 200 µg/mL, and infected with viruses. The algal extract displayed strong antiviral activity at non-toxic concentrations against all tested enveloped viruses, in particular in the virus pre-treatment against HSV-2 and HCoV-229E, with IC 50 values of 1.7 µg/mL and IC 90 of 1.8 µg/mL, respectively. However, no activity against the non-enveloped poliovirus has been detected. The inhibitory effect of the algal extract was confirmed by the quantitative RT-PCR of viral genes. Preliminary chemical profiling of the extract was performed using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS), revealing the enrichment in primary fatty acid amides (PFAA), such as oleamide, palmitamide, and pheophorbide A. These promising results pave the way for the further purification of the mixture to explore its potential role as an antiviral agent.

Breast cancer (BC) remains the leading cause of mortality in women, despite significant advancements in diagnosis. Thus, the identification of new compounds for its treatment is critical. Phytochemicals are known to exhibit anti-cancer properties. Here, we investigated the anti-proliferation potential of extracts from carrot, Calendula officinalis flower, and Aloe vera on breast cancer vs. epithelial cell lines. Various extraction methods were used, and the proliferative effect of the resulting extracts was assessed by proliferation assay on breast cancer and epithelial cell lines. Carrot, Aloe leaf, and Calendula flower extracts were extracted by hexane and methanol methods, and their semi-purified extracts were able to specifically inhibit the proliferation of breast cancer cell lines. The extract composition was investigated by colorimetric assays, UHPLC-HRMS, and MS/MS analysis. All the extracts contained monogalactosyl-monoacylglycerol (MGMG), while digalactosyl-monoacylglycerol (DGMG) and aloe-emodin were found in Aloe , and glycerophosphocholine (GPC) derivatives were identified in Calendula , except for the isomer 2 detected in carrot, suggesting that their observed different anti-proliferative properties may be associated with the different lipid compounds. Interestingly, Calendula extract was able to strongly inhibit the triple negative breast cancer MDA-MB-231 cell line proliferation (about 20% cell survival), supporting MGMG and GPC derivatives as potential drugs for this BC subtype treatment.

Lavandula austroapennina N.G. Passal., Tundis and Upon has recently been described as a new species endemic to the southern Apennines (Italy). Locally, this species has a long ethnobotanical tradition of use for curative and decoration purposes and has been the protagonist of a flourishing essential oil production chain. Currently, while this tradition has long since ended, attention to the species is necessary, with a view to enhancing marginal and rural areas, as a recovery of a precious resource to (i) get insights into its (poly)phenolic fraction and (ii) address new and innovative uses of all its organs in various application fields (e.g., cosmeceutical sector). Therefore, after field sampling and dissection of its organs (i.e., corolla, calyx, leaf, stem and root), the latter, previously deterpenated and defatted, were subjected to accelerated ultrasound extraction and the related alcoholic extracts were obtained. Chemical composition, explored by UHPLC-Q q TOF-MS/MS, and the following multivariate data analysis showed that the hydroxycinnamoyl derivatives are abundant in the leaf, stem and root, while flavonoids are more present in corolla and calyx. In particular, coumaroyl flavonoids with glyconic portion containing also hexuronyl moieties differentiated corolla organ, while yunnaneic acid D isomers and esculin distinguished root. When antiradical and reducing properties were evaluated (by means of ABTS, DPPH and PFRAP tests), a similar clustering of organs was achieved and the marked antioxidant efficacy of leaf, stem and root extracts was found. Thus, following cytotoxicity screening by MTT test on HaCaT keratinocytes, the protective effects of the organ extracts were assessed by wound closure observed after the scratch test. In addition, the extracts from corolla, leaf and stem were particularly active at low doses inducing rapid wound closure on HaCaT cells at a concentration of 1 μg/mL. The diversity in (poly)phenols of each organ and the promising bioactivity preliminarily assessed suggest further investigation to be carried out to fully recover and valorize this precious endemic vascular plant., Competing Interests: The authors declare no conflict of interest.

Wild edible plants, once consumed in times of famine or for health purposes, today represent an interesting dietary supplement, aimed at enriching local dishes and/or formulating healthy nutraceutical products. In fact, the broad content of different, and diversely bioactive, specialized metabolites therein suggests new scenarios of use which, in order to be as functional as possible, must maximize the bioactivity of these compounds while preserving their chemistry. In this context, based on a recent investigation on the metabolic profile of the organs of Calendula arvensis that highlighted that florets are abundant in flavonol glycosides and triterpene saponins, the freeze-drying encapsulation of their alcoholic extract (FE) into maltodextrin (MD) was investigated. FE-MD chemical composition was evaluated using Fourier Transform InfraRed spectroscopy (FTIR), while ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) techniques were employed to unravel FE compound preservation also during in vitro simulated digestion. The establishment of H-bonds between FE compounds and MD hydroxyl groups was in line with FE-MD biocompatibility in Caco-2 cells, while in vitro digestion mostly affected structural integrity and/or diversity. Flavonol compounds underwent deglycosylation and demethylation, while deacylation, beyond oxidation, involved triterpene saponins, which massively preserve their aglycone core.

Nowadays, chestnut by-products are gaining a lot of interest as a low-cost raw material, exploitable for developing added-value products. This is in line with suitable chestnut by-products' management, aimed at reducing the environmental impact, thus improving the chestnut industry's competitiveness and economic sustainability. In this context, with the aim of valorizing local cultivars of European chestnuts ( Castanea sativa Mill.), our attention focused on the Verdole cultivar, which has been characterized by using the UPOV guidelines for its distinctness, homogeneity, and stability. After harvesting, Verdole chestnuts were properly dissected to collect the outer and inner shells, and episperm. Each chestnut part, previously crushed, shredded, and passed through diverse sieves, underwent ultrasound-assisted extraction. The extracts obtained were evaluated for their total phenolic, flavonoid, and tannin content. The antiradical capacity by DPPH and ABTS assays, and the Fe(III) reducing power, were also evaluated. Although all the samples showed dose-dependent antioxidant efficacy, plant matrix size strongly impacted on extraction efficiency. LC-HRMS-based metabolic profiling highlighted the occurrence of different polyphenol subclasses, whose quantitative ratio varied among the chestnut parts investigated. The outer shell was more chemically rich than inner shell and episperm, according to its pronounced antioxidant activity. The polyphenol diversity of Verdole by-products is a resource not intended for disposal, appliable in the nutraceutical sector, thus realizing a new scenario in processing chestnut waste.

As part of a project aimed at promoting the use of Calendula arvensis (Vaill.) L. (field marigold, Asteraceae) phytocomplexes in cosmeceutical formulations, the chemical composition in apolar specialized metabolites is herein elucidated. Furthermore, the screening of the cytotoxicity of the apolar extracts was evaluated in order to underline their safety as functional ingredients for cosmetics. After dissection of Calendula organs (florets, fruits, leaves, bracts, stems, and roots), ultrasound-assisted maceration in n -hexane as an extracting solvent allowed us to obtain oil-like mixtures, whose chemical composition has been highlighted through a UHPLC-ESI-Q q TOF-MS/MS approach. Twenty-nine metabolites were tentatively identified; different compounds, among which the well-known poly-unsaturated fatty acids, and oxylipins and phosphatides were detected for the first time in Calendula genus. The screening of the dose-response cytotoxicity of the apolar extracts of C. arvensis highlighted the concentration of 10 μg/mL as the most suitable for the formulation of cosmeceutical preparations. Sera enriched with leaf and fruit apolar extracts turned out to have the best activity, suggesting it can be used as a new source in skin care thanks to their higher content in fatty acids.

Edible, plant-derived foodstuffs are recognized as precious sources of polyphenol compounds, whose consumption has proven to have multiple beneficial effects on human health. However, the awareness that cooking processes are able to induce quali-quantitatively changes in their native occurrence and that their bioavailability after food ingestion is poor led the research to move toward the preparation of nutraceutical supplements aimed at maximizing their content by effective extractive techniques and protecting them from degradation. The present work fits into this context, proposing a green, ready-to-use formulation of capitula, stems, and leaves of Algerian artichokes, in which natural deep eutectic solvents were exploited as extracting solvents but not removed at the end of the process. MTT test on the Caco-2 cell line highlighted that mitochondrial redox activity inhibition was absent below the 50 µg/mL tested dose. Simulated in vitro digestion was used as a predictive model for formulation bioaccessibility, where the joint approach with UHPLC-HRMS techniques allowed to define the release of each polyphenol from the investigated matrices. The capitula-based sample was the richest one in flavonoids, especially luteolin and apigenin glycosides, which survived in the intestinal digesta. On the contrary, simple phenols characterized the stem sample, whose release was mainly in the gastric chyme.

Castanea sativa Mill. (Fagaceae) is a deciduous tree grown for its wood and edible fruits. Chestnut processing produces residues (burs, shells, and leaves) exploitable for their diversity in bioactive compounds in animal nutrition. In fact, plant-specialized metabolites likely act as rumen modifiers. Thus, the recovery of residual plant parts as feed ingredients is an evaluable strategy. In this context, European chestnut leaves from northern Germany have been investigated, proving to be a good source of flavonoids as well as gallo- and ellagitannins. To this purpose, an alcoholic extract was obtained and an untargeted profiling carried out, mainly by means of ultra-high-performance liquid chromatography/high-resolution tandem mass spectrometry (UHPLC-HR MS/MS) techniques. To better unravel the polyphenol constituents, fractionation strategies were employed to obtain a lipophilic fraction and a polar one. This latter was highly responsive to total phenolic and flavonoid content analyses, as well as to antiradical (DPPH ● and ABTS +● ) and reducing activity (PFRAP) assays. The effect of the alcoholic extract and its fractions on rumen liquor was also evaluated in vitro in terms of fermentative parameter changes and impact on methanogenesis. The data acquired confirm that chestnut leaf extract and the fractions therefrom promote an increase in total volatile fatty acids, while decreasing acetate/propionate ratio and CH 4 production.

The genus Quercus supplies a large amount of residual material (e.g., bark, acorns, leaves, wood), the valorization of which can favor a supply of antioxidant polyphenols to be used in the pharmaceutical, nutraceutical, or cosmeceutical sector. The recovery of specialized metabolites could also benefit livestock feeding, so much so that polyphenols have gained attention as rumen fermentation modifiers and for mitigating the oxidative imbalance to which farm animals are subject. In this context, leaves of Quercus robur L. from Northern Germany were of interest and the alcoholic extract obtained underwent an untargeted profiling by means of ultra-high-performance liquid chromatography/high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) techniques. As triterpenes and fatty acids occurred, the alcoholic extract fractionation pointed out the obtainment of a polyphenol fraction, broadly constituted by coumaroyl flavonol glycosides and condensed tannins. Total phenol, flavonoid and condensed tannins content assays, as well as antiradical (DPPH ● and ABTS +● ) and reducing activity (PFRAP) were carried out on the alcoholic extract and its fractions. When the effects on rumen liquor was evaluated in vitro in terms of changes in fermentation characteristics, it was observed that oak leaf extract and its fractions promoted an increase in total volatile fatty acids and differently modulated the relative content of each fatty acid.

There is growing interest in specialized metabolites for fortification strategies in feed and/or as an antioxidant, anti-inflammatory and antimicrobial alternative for the containment of disorders/pathologies that can also badly impact human nutrition. In this context, the improvement of the diet of ruminant species with polyphenols and the influence of these compounds on animal performance, biohydrogenation processes, methanogenesis, and quality and quantity of milk have been extensively investigated through in vitro and in vivo studies. Often conflicting results emerge from a review of the literature of recent years. However, the data suggest pursuing a deepening of the role of phenols and polyphenols in ruminant feeding, paying greater attention to the chemistry of the single compound or to that of the mixture of compounds more commonly used for investigative purposes.

The identification of a natural compound with selectively differential radiomodulating activity would arguably represent a valuable asset in the striving quest for widening the therapeutic window in cancer radiotherapy (RT). To this end, we fully characterized the chemical profile of olive tree leaf polyphenols from the Caiazzana cultivar (OLC), autochthonous to the Campania region (Italy), by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HR-MS). Oleacein was the most abundant molecule in the OLC. Two normal and two cancer cells lines were X-ray-irradiated following 24-h treatment with the same concentration of the obtained crude extract and were assessed for their radioresponse in terms of micronucleus (MN) induction and, for one of the normal cell lines, of premature senescence (PS). Irradiation of pre-treated normal cells in the presence of the OLC reduced the frequency of radiation-induced MN and the onset of PS. Conversely, the genotoxic action of ionising radiation was exacerbated in cancer cells under the same experimental conditions. To our knowledge, this is the first report on the dual action of a polyphenol-rich olive leaf extract on radiation-induced damage. If further confirmed, these findings may be pre-clinically relevant and point to a substance that may potentially counteract cancer radioresistance while reducing RT-associated normal tissue toxicity.

Over the years, many materials have been used to restore buildings, paintings, ceramics, and mosaic pieces exhibiting different types of dyes and colour hues. Recently, geopolymers have been used for restoration purposes owing to their high chemical and mechanical resistance. In this work, white metakaolin was used to obtain white geopolymers, cured at 25 and 40 °C, as bulk materials to be coloured with synthetic organic dyes, i.e., bromothymol blue, cresol red, phenolphthalein, and methyl orange. These dyes were added during the fresh paste preparation to obtain dyed geopolymeric solids. Ionic conductivity and pH measurement confirmed the chemical stability of the consolidated materials, while FT-IR analyses were used to follow the geopolymerisation occurrences at different ageing times (from 7 to 56 days). Finally, the colour hues and properties were assessed in the CIELAB colour space before and after immersion in water., Competing Interests: The authors declare no conflict of interest.

The aim of this study was to evaluate the cytotoxic activity and the chemical composition of the tomato extracts coming from, Pomodoro Giallo and San Marzano Cirio 3, and then to evaluate the potential changes when plants were grown in soils contaminated by cadmium, chromium and lead. Extracts were investigated by UHPLC-HRMS and UV-Vis. Cell viability (CellTiter-Glo Luminescent assay), enzyme aldehyde dehydrogenase activity (ALDEFLOUR Assay), cell cycle progression (Accuri C6 Flow Cytometer), apoptosis and necrosis (Annexin V-FITC assay) were evaluated on two gastric cancer (AGS and NCI-N87) and two colorectal cancer (HT-29 and HCT 116) cell lines. Different content of polyphenol and carotenoid constituents was observed. Extracts from uncontaminated soil induced cytotoxic activity towards all selected cancer cells, while extracts coming from contaminated soils showed the aberrant phenotype increased in colorectal cancer cells. Chloroform extracts exerted the highest cytotoxic activity. AGS and HT-29 were the most sensitive to cell cycle arrest and to apoptosis. No necrotic effect was observed in HCT 116. The contrasting effects on cancer cells were observed based on tomato variety, the extract polarity, heavy metal identity, and tested cell line. The investigation of potential adverse health effects due to Cd in the fruits should be explored., (© 2022. The Author(s).)

Nowadays, hemp farmers are facing an urgent problem related to plant stem disposal after seed harvesting. In this work, the commonly discarded epidermis and cuticle of hemp stems were valorized, turning them towards a sustainable recycling and reuse, contributing to the circular economy concept. Cellulose deprived of amorphous regions was obtained by a green process consisting of an ethanolic ultrasound-assisted maceration followed by mild bleaching/hydrolysis. The obtained hemp cellulose was esterified with citric acid resulting in a 1.2-fold higher crystallinity index and 34 ∘C lower T g value compared to the non-functionalized hemp cellulose. Green innovative biocomposite films were developed by embedding the modified cellulose into PLA by means of an extrusion process. The structural and morphological characterization of the obtained biocomposites highlighted the functionalization and further embedment of cellulose into the PLA matrix. Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy (ATR-FTIR) results suggested physical and chemical interactions between PLA and the organic filler in the biofilms, observing a homogeneous composition by Field Emission-Scanning Electron Microscopy (FESEM). Moreover, some increase in thermal stability was found for biocomposites added with 5%wt of the hemp cellulose filler. The obtained results highlighted the feasible recovery of cellulose from hemp stem parts of disposal concern, adding value to this agro-waste, and its potential application for the development of novel biocomposite films to be used in different applications.

Cannabidiolic acid (CBDA) is the main precannabinoid in industrial hemp. It represents a common constituent of hemp seed oil, but mainly abundant in the aerial parts of the plant (including their processing waste). Thus, the optimization of fast and low-cost purification strategies is mandatory, as well as a deep investigation on its nutraceutical and cosmeceutical properties. To this purpose, CBDA content in hemp seed oil is evaluated, and its recovery from wasted leaves is favorably achieved. The cytotoxicity screening towards HaCaT cells, by means of MTT, SRB and LDH release assays, suggested it was not able to decrease cell viability or perturb cell integrity up to 10 μM concentration. Thus, the ability of CBDA to differentially modulate the release of proinflammatory cytokines and chemokines mediators has been evaluated, finding that CBDA decreased IFN-γ, CXCL8, CXCL10, CCL2, CCL4 and CCL5, mostly in a dose-dependent manner, with 10 μM tested concentration exerting the highest activity. These data, together with those from assessing antimicrobial activity against Gram(+) and Gram(-) bacteria and the antibiofilm formation, suggest that CBDA is able to counteract the inflammatory response, also preventing bacteria colonization.

In recent years, animal husbandry has aimed at improving the conditions of livestock animals useful for humans to solve environmental and health problems. The formulation of animal feeds or supplements based on antioxidant plant compounds is considered a valuable approach and an alternative for livestock productivity. Forest biomass materials are an underestimated source of polyphenolic compounds whose sustainable recovery could provide direct benefits to animals and, indirectly, human nutrition. In this context, an alcohol extract from leaves of Fagus sylvatica L. was first investigated through an untargeted ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) approach. Then, it was fractionated into a fatty acid-rich and a polyphenolic fraction, as evidenced by total lipid, phenol, and flavonoid content assays, with antiradical and reducing activity positively correlated to the latter. When tested in vitro with rumen liquor to evaluate changes in the fermentative parameters, a significant detrimental effect was exerted by the lipid-rich fraction, whereas the flavonoid-rich one positively modulated the production of volatile fatty acids (i.e., acetate, butyrate, propionate, etc.).

Purpose: One of the obstacles to the application of Boron Neutron Capture Therapy (BNCT) and Proton Boron Fusion Therapy (PBFT) concerns the measurement of borated carriers' biodistribution. The objective of the present study was to evaluate the in vitro internalization of the 19 F-labelled p-boronophenylalanine ( 19 F-BPA) in the human cancer pancreatic cell line (PANC-1) for the potential application of BNCT and PBFT in pancreatic cancer. The 19 F-BPA carrier has the advantage that its bio-distribution may be monitored in vivo using 19 F-Nuclear Magnetic Resonance ( 19 F NMR)., Materials and Methods: The 19 F-BPA internalization in PANC-1 cells was evaluated using three independent techniques on cellular samples left in contact with growing medium enriched with 13.6 mM 19 F-BPA corresponding to a 11 B concentration of 120 ppm: neutron autoradiography, which quantifies boron; liquid chromatography hyphenated to tandem mass spectrometry and UV-Diode Array Detection (UV-DAD), which quantifies 19 F-BPA molecule; and 19 F NMR spectroscopy, which detects fluorine nuclei., Results: Our studies suggested that 19 F-BPA is internalized by PANC-1 cells. The three methods provided consistent results of about 50% internalization fraction at 120 ppm of 11 B. Small variations (less than 15%) in internalization fraction are mainly dependent on the proliferation state of the cells., Conclusions: The ability of 19 F NMR spectroscopy to study 19 F-BPA internalization was validated by well-established independent techniques. The multimodal approach we used suggests 19 F-BPA as a promising BNCT/PBFT carrier for the treatment of pancreatic cancer. Since the quantification is performed at doses useful for BNCT/PBFT, 19 F NMR can be envisaged to monitor 19 F-BPA bio-distribution during the therapy., (Copyright © 2021 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Calendula arvensis (Vaill.) L. (field marigold, Asteraceae) is an alimurgic plant, whose flowers and leaves are a common part of local food dishes. The diversity in polar specialized metabolites is herein unraveled, with the aim to further promote and valorize the food use of the plant. To this purpose, following the plant dissection of its organs (florets, fruits, leaves, bracts, stems, and roots), ultrasound assisted maceration has been employed in order to recover phenols and polyphenols. Through an untargeted UHPLC-HR MS (Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry) approach, and deeper investigation of the fragmentation patterns of each compound by tandem mass spectrometry, the florets' constitution in triterpene saponins and flavonol glycosides has been highlighted, whereas hydroxycinnamoyl compounds are mainly in bracts and fruits. The antiradical and reducing capabilities of the organs' extracts have been assessed, and data acquired have been analyzed by cluster analysis, which allowed bracts and fruits to be observed, despite their negligible food use, as the most active extracts. Chemical and antioxidant data on the diverse organs of field marigold suggest new investigative food and nutraceutical scenarios of this plant, also revalorizing and preserving its traditional uses.

Food containers made from glass are separately collected from urban solid waste at 76% in most parts of Europe. The cullet glass finds its way to re-melting, while the debris is often disposed of. With this contribution, we suggest an upcycling process where glass debris is simply ground without any washing operation and added to an alkali-activated paste. Metakaolin-based geopolymer mortar added with coarsely ground glass waste as fine aggregate has been prepared via alkali activation with NaOH and Na-silicate. After 7, 14 and 28 days of room temperature curing time, the 3D geopolymer network was investigated by Fourier-transform infrared spectroscopy (FT-IR). Vibrational spectra revealed the geopolymerization occurrences, results which have been supported by both FT-IR deconvoluted spectra and thermogravimetric analysis (TGA). Finally, the antibacterial properties were investigated against both gram-negative ( E. coli ) and gram-positive ( E. faecalis ) bacterial strains. The results suggest the ability of the 28 days cured geopolymers to inhibit the growth of the gram-negative bacterium assayed.

Currently, radiotherapy is one of the most effective strategies to treat cancer. However, deleterious toxicity against normal cells indicate for the need to selectively protect them. Reactive oxygen and nitrogen species reinforce ionizing radiation cytotoxicity, and compounds able to scavenge these species or enhance antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) should be properly investigated. Antioxidant plant-derived compounds, such as phenols and polyphenols, could represent a valuable alternative to synthetic compounds to be used as radio-protective agents. In fact, their dose-dependent antioxidant/pro-oxidant efficacy could provide a high degree of protection to normal tissues, with little or no protection to tumor cells. The present review provides an update of the current scientific knowledge of polyphenols in pure forms or in plant extracts with good evidence concerning their possible radiomodulating action. Indeed, with few exceptions, to date, the fragmentary data available mostly derive from in vitro studies, which do not find comfort in preclinical and/or clinical studies. On the contrary, when preclinical studies are reported, especially regarding the bioactivity of a plant extract, its chemical composition is not taken into account, avoiding any standardization and compromising data reproducibility.

European beech ( Fagus sylvatica L.) is a deciduous tree, widely distributed in Europe and largely appreciated for its wood and nutritive nuts. Beech leaf also enjoys food use as salad, but an understanding of its nutraceutical value is still far from being achieved. Indeed, and also taking into account beech leaf as a consistent biomass residue available beechwood production and use, it needs to be explored as a valuable renewable specialized source of bioactive molecules. In this context, an untargeted ultra-high-performance liquid chromatography hyphenated with high resolution mass spectrometry (UHPLC-HRMS) approach was favorably applied to a beech leaf alcoholic extract, which also was evaluated for its antiradical capability (by means of assays based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and [2,2'-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid)] (ABTS) radical cation) and its ferric ion reducing power. Redox mitochondrial activity towards Caco-2 cells paved the way to explore the extract's capability to inhibit intracellular Reactive Oxygen Species (ROS) using 2',7'dichlorofluorescin diacetate (DCFH-DA) assay. Hydroxycinnamoyl derivatives, mainly belonging to the chlorogenic acid class, and flavonoids were the main constituents. Uncommon flavanone C -glycosides were also found, together with a plentiful flavonol diversity. Cell-free and cell-based assays highlight its dose-dependent antioxidant efficacy, providing a foundation for further investigation of beech leaf constituents and its valorization and use as a reservoir of bioactive natural products with potential nutraceutical applications.

The interest in industrial hemp-based products and by-products to be utilized in food and nutraceutical sector is strictly linked to the demand for improved analytical methods to rapidly discriminate acid phytocannabinoid isomers. Indeed, the differentiation of acid phytocannabinoids, also named pre-cannabinoids, is not properly exploited and valued until now, and it is challenging. Herein, using high-resolution MS/MS, the most common pre-cannabinoids with the resorcinol core linked to the alkyl five carbons chain were deeply investigated in terms of their reactivity to collision-induced dissociation, gaining key data on the integrated energy framework of their dissociation pathway. In fact, CBD-, THC- and CBC-type pre-cannabinoids could be discriminated based on the base peak identity, and the intensity of common fragment ions, when collision energy fragmented precursor ions by 70-75 %. In particular, energy-resolved CID mass spectra highlighted that fragmentation occurs, unrelatedly to alkyl chain length, at phenolic and monoterpenic moieties levels. Accordingly, this tool is effective for further differentiating pre-cannabinoid homologues, from methyl- up to heptyl-homologues, getting new insight in acid cannabinoids heritage of hemp and its products., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dietary supplements based on Teucrium chamaedrys L. subsp. chamaedrys aerial parts were banned, due to the hepatotoxicity of furan-containing neo -clerodane constituents. Indeed, the plant leaf content in phenolic compounds could be further exploited for their antioxidant capability. Accordingly, bio-guided fractionation strategies have been applied, obtaining seven partially purified extracts. These latter were chemically investigated through 1D and 2D NMR techniques and tested for their antiradical, reducing and cytotoxic capability. Data acquired highlighted that, through a simple phytochemical approach, a progressive neo -clerodane depletion occurred, while maximizing phenylethanoid glycosides in alcoholic fractions. Thus, although the plant cannot be used as a botanical remedy as such, it is suggested as a source of healthy compounds, pure or in mixture, to be handled in pharmaceutical, nutraceutical and/or cosmeceutical sectors.

This Special Issue, entitled "Food Bioactives: Chemical Challenges and Bio-Opportunities", was born with the aim of attracting contributions on analytical challenges in food bioactives' chemistry and bioactivity, which form the basis of proper bio-opportunities [...].

Chickpea ( Cicer arietinum L.) from Valle Agricola is a legume cultivated in Southern Italy whose intake is strictly linked to rural traditions. In order to get new biochemical insight on this landrace and to promote its consumption and marketing, nutritional values (moisture content, total proteins, lipids, total and free amino acids) and metabolic traits are deeply investigated. Valle Agricola chickpea is nutritionally rich in proteins (19.70 g/100 g) and essential amino acids (7.12 g/100 g; ~40% of total). Carbohydrates, whose identity was unraveled by means of UHPLC-HR MS/MS analysis, were almost 60% of chemicals. In particular, a di-galactosylglycerol, a pinitol digalactoside, and a galactosylciceritol were found as constitutive, together with different raffinose-series oligosaccharides. Although lipids were the less constitutive compounds, glycerophospholipids were identified, while among free fatty acids linoleic acid (C18:2) was the most abundant, followed by oleic (C18:1) and palmitic (C16:0) acids. Isoflavones and hydroxybenzoic acid derivatives were also detected. Valle Agricola chickpeas showed very good levels of several mineral nutrients, especially magnesium (164 mg/100 g), potassium (748 mg/100 g), calcium (200 mg/100 g), zinc (4.20 mg/100 g) and manganese (0.45 mg/100 g). The boiling process favorably decreases anti-trypsin and anti-chymotrypsin activities, depleting this precious seed of its intrinsic antinutritional factors.

Theobroma cacao provides precious products such as polyphenol-rich beans that are useful for nutraceutical purposes. The geographical area may influence the chemical composition of raw cocoa beans in terms of the polyphenols and biological qualities of the products. This work aimed to investigate the biological properties and the chemical composition of two different samples of Criollo var. cocoa raw beans coming from two areas (Indonesia; Peru). Beans underwent biphasic extraction obtaining lipophilic and hydroalcoholic extracts. The extracts were tested for antiradical, antimutagenic, and antigenotoxic effects. Cell viability inhibition toward breast, gastric/esophageal colorectal adenocarcinoma, and hepatoblastoma human cell lines was evaluated. Extracts were chemically investigated through UV-Vis spectroscopy and ultra-high-pressure liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-Q q TOF MS/MS). Results showed that the Indonesian bean hydroalcoholic extracts were able to scavenge 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) cation radical better than the Peruvian hydroalcoholic extracts (ECs 50 : 72.63 vs. 322.20 μg/mL). Extracts showed antimutagenic and antigenotoxic activity. The viability inhibitory effect on breast and hepatic cancer cells was reached only for the Indonesian hydroalcoholic extracts at hundreds of μg/mL. Phenylpropenoyl-L-amino acids, hydroxycinnamoyl aminoacids conjugates, and procyanidin compounds were found mainly in the hydroalcoholic extracts, whereas fatty acids and lyso-phospholipids were found mainly in lipophilic fractions. Fatty acid and ( epi )catechins appeared to be affected by different environmental conditions of the geographical areas.

The metabolite profiling of plant extracts always represents an exciting challenge, as the chemical diversity of natural products is still far beyond the researchers' imagination, even focusing on a plant that is thought to have already been broadly investigated. Herein UHPLC-HRMS/MS techniques were applied to an alcoholic crude extract from nettle leaves and proved to be a precious tool for the disclosure of secondary metabolites never found before. Hydroxycinnamic acid derivatives were the most representative constituents, with a 2-caffeoilisocitric acid cyclodimer described for the first time, besides four C-glycosylated flavones, bearing a 3-hydroxy-3-methylglutaryl function. This deep investigation paves the way for the isolation and full characterization of these molecules by means of spectroscopic techniques. Moreover, based on preliminary cytotoxicity evaluation, further research on the use of this nettle extract as a valuable nutraceutical product is encouraged., Competing Interests: Declaration of Competing Interest The authors declare no financial or other conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The epidemic, caused by SARS-CoV-2 at the beginning of 2020, led us to a serious change in our lifestyle that for about three months has confined us to our homes, far from our laboratory routine. In this period, the belief that the work of a researcher should never stop has been the driving force in writing the present paper. It aims at reviewing the recent scientific knowledge about in vitro experimental data that focused on the antiviral role of phenols and polyphenols against different species of coronaviruses (CoVs), pointing up the viral targets potentially involved. In the current literature scenario, the papain-like and the 3-chymotrypsin-like proteases seem to be the most deeply investigated and a number of isolated natural (poly)phenols has been screened for their efficacy.

After a long period defined by prohibition of hemp production, this crop has been recently re-evaluated in various industrial sectors. Until now, inflorescences have been considered a processing by-product, not useful for the food industry, and their disposal also represents an economic problem for farmers. The objects of the present work are coffee blends enriched with shredded inflorescences of different cultivars of industrial hemp that underwent solid/liquid extraction into the Italian "moka" coffee maker. The obtained coffee drinks were analyzed by Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS) tools for their quali-quantitative phytocannabinoid profiles. The results showed that they are minor constituents compared to chlorogenic acids and caffeine in all samples. In particular, cannabidiolic acid was the most abundant among phytocannabinoids, followed by tetrahydrocannabinolic acid. Neither Δ 9 -tetrahydrocannabinol (THC) nor cannabinol, its main oxidation product, were detected. The percentage of total THC never exceeded 0.04%, corresponding to 0.4 mg/kg, far below the current maximum limits imposed by the Italian Ministry of Health. This study opens up a new concrete possibility to exploit hemp processing by-products in order to obtain drinks with high added value and paves the way for further in vitro and in vivo investigations aimed at promoting their benefits for human health.

Although hemp seed (HS) oil is characterized by more than 80% polyunsaturated fatty acids (PUFAs), a very high ω-6-to-ω-3 ratio is not a popular commodity. The aim of this work was to provide useful data about the bioactive components and cannabidiolic acid content in thirteen different commercial hemp seed oils. The investigated HS oils showed a good ω-6/ω-3 ratio, ranging from 1.71 to 2.27, massively differed in their chlorophylls (0.041-2.64 µg/g) and carotenoids contents (0.29-1.73 µg/g), as well as in total phenols (22.1-160.8 mg Gallic Acid Equivalents (GAE)/g) and tocopherols (3.47-13.25 mg/100 g). Since the high content of PUFAs in HS oils, photo-oxidative stability was investigated by determining the Thiobarbituric Acid Reactive Substances (TBARS) assay and extinction coefficient K232 and K270 after the photo-oxidative test. The percentage of increase in K232 and K270 ranged from 1.2 to 8.5% and from 3.7 to 26.0%, respectively, indicating good oxidative stability, but TBARS showed a 1.5- to 2.5-fold increase in oxidative behavior when compared to the initial values. Therefore, the diversity in bioactive compounds in HS oils, and their high nutritional value, suggest the need for a disciplinary booklet that well defines agronomic and post-harvest management conditions for achieving a good food objective.

Cannabidiolic acid (CBDA) is the main phytocannabinoid in fiber and seed-oil hemp ( Cannabis sativa L.) plants, but its potential health-related capabilities have been masked for years by a greater scientific interest towards its neutral derivative cannabidiol (CBD). This review aims to collect from the literature and critically discuss all the information about this molecule, starting from its biosynthesis, and focusing on its bioactivity, as an anti-inflammatory, anti-emetic, anti-convulsant, and anti-cancerogenic drug. Furthermore, in the awareness that, despite its multiple bioactive effects, currently poor efforts have been made to achieve its reliable purification, herein, we propose a relatively simple, fast, and inexpensive procedure for its recovery from pollen of industrial hemp cultivars. Spectroscopic and spectrometric techniques allowed us to unequivocally identify pure isolated CBDA and to distinguish it from the constitutional isomer tetrahydrocannabinolic acid (THCA-A)., Competing Interests: The authors declare no conflict of interest

Total phenolic content and antioxidant activity of polar extracts of edible resources from Fedora hemp cultivar ( Cannabis sativa L.), namely seed, flour and oil, were evaluated. The main components in the polar extracts were identified using HPLC-DAD and HPLC-ESI-MS/MS. As expected, the molecular profile of components from seeds and flour was strictly similar, dominated by N-trans-caffeoyltyramine. The profile of oil polar extracts contained hydroxycinnamic acid derivatives and cannabinoids at lower extent. While the extracts from hemp seed and flour did not interfere with growth of Caco-2 and HT-29 cell, the one from oil (150 µg/mL) significantly reduced cell viability after 24 h of treatment. This effect was associated with the activation of apoptotic cell death and was independent from the antioxidant capacity of the oil polar extract. Notably, HT-29 cells differentiated with sodium butyrate were not sensitive to the cytotoxic effect of the oil extract.

Marketed green teas (GTs) can highly vary in their chemical composition, due to different origins, processing methods, and a lack of standardization of GT-based products. Consequently, biological activities become difficult to correlate to the presence/content of certain constituents. Herein, ultra-high-performance liquid chromatography (UHPLC) combined with high-resolution tandem mass spectrometry (HR MS/MS) was successfully applied to six commercial GT products, extracted by ethanol sonication, to disclose their polyphenol profile beyond the well-known catechins. The relative abundance of each class of metabolites was correlated to antiradical and antilipoperoxidant data through hierarchical clustering analysis, since it reasonably affects the beneficial properties of the product that reaches the consumer. The thiobarbituric acid reactive substances (TBARS) assay demonstrated that GT extracts effectively counteracted the UV-induced lipoperoxidation of hemp oil, which is highly rich in Polyunsaturated Fatty Acids (PUFAs), and therefore highly unstable. The Relative Antioxidant Capacity Index (RACI) comprehensively emphasized that gunpower and blend in filter GTs appeared to be the less active matrices, and except for a GT-based supplement, the Sencha GT, which was particularly rich in flavonol glycosides, was the most active, followed by Bancha GT.

The weak but noteworthy presence of (poly)phenols in hemp seeds has been long overshadowed by the essential polyunsaturated fatty acids and digestible proteins, considered responsible for their high nutritional benefits. Instead, lignanamides and their biosynthetic precursors, phenylamides, seem to display interesting and diverse biological activities only partially clarified in the last decades. Herein, negative mode HR-MS/MS techniques were applied to the chemical investigation of a (poly)phenol-rich fraction, obtained from hemp seeds after extraction/fractionation steps. This extract contained phenylpropanoid amides and their random oxidative coupling derivatives, lignanamides, which were the most abundant compounds and showed a high chemical diversity, deeply unraveled through high resolution tandem mass spectrometry (HR-MS/MS) tools. The effect of different doses of the lignanamides-rich extract (LnHS) on U-87 glioblastoma cell line and non-tumorigenic human fibroblasts was evaluated. Thus, cell proliferation, genomic DNA damage, colony forming and wound repair capabilities were assessed, as well as LnHS outcome on the expression levels of pro-inflammatory cytokines. LnHS significantly inhibited U-87 cancer cell proliferation, but not that of fibroblasts, and was able to reduce U-87 cell migration, inducing further DNA damage. No modification in cytokines' expression level was found. Data acquired suggested that LnHS acted in U-87 cells by inducing the apoptosis machinery and suppressing the autophagic cell death.

Seven previously undescribed sesquiterpene lactones, three known sesquiterpene lactones (ixerin D, 15-p-hydroxyphenylacetyllactucin, and 15-p-hydroxyphenylacetyllactucin-8-sulfate), and two known quinic acid derivatives (3-O-feruloylquinic acid and 3,5-di-O-caffeoylquinic acid) were isolated from Sonchus palustris L. roots. Four formerly undescribed compounds were elucidated to be 3β,14-dihydroxycostunolide-3-O-β-D-glucopyranosyl-(2-O-p-hydroxyphenylacetyl)-14-O-p-hydroxyphenylacetate, 15-p-methoxyphenylacetyllactucin, 15-p-methoxyphenylacetyllactucin-8-sulfate, and 8-p-hydroxyphenylacetyllactucin-15-sulfate. Additionally, three undescribed conjugates of lactucin and a eudesmanolide type sesquiterpenic acid, sonchpalustrin, 4″-O-methylsonchpalustrin, and isosonchpalustrin, were characterized. The structures of the newly discovered natural products were elucidated using 1D and 2D NMR spectroscopy and UHPLC-HRMS. 15-p-Hydroxyphenylacetyllactucin and 15-p-methoxyphenylacetyllactucin showed significant in vitro cytotoxicity against CEM and BJ cells with IC 50 values ranging from 3.9 to 9.8 μM. Compounds 3 and 4 showed also strong anti-inflammatory activity in vitro., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The sol-gel route represents a valuable technique to obtain functional materials, in which organic and inorganic members are closely connected. Herein, four hybrid materials, containing caffeic acid entrapped in a silica matrix at 5, 10, 15, and 20 wt.%, were synthesized and characterized through Fourier-Transform Infrared (FT-IR) and Ultraviolet-Visible (UV-Vis) spectroscopy. FT-IR analysis was also performed to evaluate the ability to induce the hydroxyapatite nucleation. Despite some structural changes occurring on the phenol molecular skeleton, hybrid materials showed scavenging properties vs. 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2'-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid) radical cation (ABTS• + ), which was dependent on the tested dose and on the caffeic acid wt.%. The SiO 2 /caffeic acid materials are proposed as valuable antibacterial agents against Escherichia coli and Enterococcus faecalis .

Nowadays, the research for secondary metabolites with health promoting effects in countering or slowing-down chronic and degenerative diseases (e.g. cancer, cardiovascular, and neurodegenerative diseases) identify phenols and polyphenols, widespread and mostly copious in dietary plant sources, as beneficial for human health. These compounds, as intrinsically antioxidant, are claimed as nutraceuticals with preventive efficacy in offsetting oxidant species over-genesis in normal cells, and with the potential ability to halt or reverse oxidative stress-related diseases. In this context, pure (poly)phenols and/or their herbal/food complexes were found to exert both anti- and pro-oxidant activities, suggesting also a promising chemopreventive efficacy. In fact, different evidence further highlights their ability to induce apoptosis, growth arrest, DNA synthesis inhibition and/or modulation of signal transduction pathways. Indeed, a full understanding of the phenolic and polyphenolic composition of plant species, which still now represent their inestimable and worth exploring source, is an important challenge, which today can and must be favourably pursued in the consciousness that the bioactivity of a plant extract is always in its chemistry. To reach this purpose a number of new and advanced techniques are available for extraction, purification and structural identification purposes, but, taking into account how, when and where (poly)phenols are biosynthesized, their use must be highly rationalized. This is particularly true for mass spectrometry techniques which, although representing one of the most powerful tools and in continuous evolution in this era, often suffer from an automatism that does not give justice to the chemical goodness of a plant species and particularly those of nutraceutical interest. This review will deepen into polyphenol research, focusing on biosynthesis, analytical approaches for a conscious exploitability of nutraceutical plant extracts rich in antioxidant and anti-inflammatory polyphenols and/or pure isolated polyphenols., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ageritin is the first reported ribotoxin-like protein from basidiomycetes fungi. It can induce ribosomal integrity damage and translation block, and interferes with mitochondrial redox activity of some glioma and neuroblastoma cell lines. Herein, Ageritin has been investigated as a valuable neurotoxin towards either undifferentiated or retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cells showing a selective cell toxicity against undifferentiated cells. MTT and sulforhodamine B (SRB) assays highlighted that Ageritin markedly decreases the mitochondrial redox activity and viability of undifferentiated cells, meanwhile inducing evident morphological changes eliciting neuronal-like appearance in these cells. Data from lactate dehydrogenase release assay, cytofluorimetric analysis and caspase-3 enzymatic activity measurement suggest that Ageritin promotes cell death through a caspase-dependent apoptotic pathway. The Z-VAD-FMK caspase inhibitor was able to prevent this apoptotic pathway activation. Based on the interesting behaviour of Ageritin vs. SH-SY5Y cells, the development of a scale-up procedure to obtain the purified protein in larger amounts (yield 2.5 mg per 100 g) has been optimized.

Leaves of Vitis vinifera data. As the localization of saccharidic moiety in glycuronide compounds proved to be difficult due to the lack of well-established fragmentation pattern and/or the absence of characteristic key fragments, to obtain useful MS information and to eliminate matrix effect redundancies, the isolation of the most abundant extract's compound was achieved. HR-MS/MS spectra of the compound, quercetin-3- 2 data. As the localization of saccharidic moiety in glycuronide compounds proved to be difficult due to the lack of well-established fragmentation pattern and/or the absence of characteristic key fragments, to obtain useful MS information and to eliminate matrix effect redundancies, the isolation of the most abundant extract's compound was achieved. HR-MS/MS spectra of the compound, quercetin-3- O -glucuronide, allowed us to thoroughly rationalize its fragmentation pattern, and to unravel the main differences between MS/MS behavior of flavonol glycosides and glycuronides. Furthermore, cytotoxicity assessment on the (poly)phenol rich fraction and the pure isolated compound was carried out using central nervous system cell lines. The chemoprotective effect of both the (poly)phenol fraction and quercetin-3- O -glucuronide was evaluated., Competing Interests: The authors declare no conflicts of interest.

Nowadays, advanced extraction techniques and highly sensitive metabolic profiling methods are effectively employed to get new information on plant chemical constituents. Among them wild medicinal plants or their parts, with large and ancient use in folk medicine, are investigated for their potential functional use and cultivation. In this context, Inula viscosa leaves engaged our attention. A simple experimental design, based on Soxhlet extraction and chromatographic fractionation, allowed us to obtain the investigated polyphenol fraction (IvE). UHPLC-HRMS analyses revealed shikimoyl depsides of caffeic acid and unusual dihydrobenzofuran lignans as main secondary metabolites. These compounds, together with cinchonain-type phenols, and hydroxycinnamoyl flavonol glycosides, are reported for the first time in inula. Overall, forty-three secondary metabolites were identified. The extract exerted a remarkable antiradical activity towards DPPH • and ABTS +• . Furthermore, it was able to inhibit cell viability and mitochondrial redox activity of neuroblastoma, hepatoblastoma and colon carcinoma cells, whereas it did not affect cell density of HaCaT cells immortalized human keratinocytes. As detected by the oxidant-sensing probe 2',7'-dichlorodihydrofluorescein diacetate, the inhibitory responses seemed to be related to IvE-induced increase of intracellular reactive oxygen species (ROS). The obtained results highlighted that inula leaves, nowadays even undervalued and unexplored, could be considered a renewable source of nutraceutical compounds., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

New organic-inorganic hybrid materials were synthesized by an acid catalysed sol-gel approach, using silicon alkoxide and low molecular weight polyethylene glycol (PEG400) as inorganic and organic precursor, respectively. Chlorogenic acid (CGA), an antioxidant natural phenol compound, enriched further the organic component. Hybrids synthesized, all identical in terms of their starting materials, but differing in terms of their relative proportions, were characterized by means of Fourier Transform InfraRed (FTIR) measurements, UV-Vis spectroscopy, and UHPLC-HRMS analysis. The preservation of the intrinsic chlorogenic acid ability to scavenge, in a dose-dependent manner, radical species was investigated by directly exposing the hybrids to DPPH radical and ABTS radical cation. The relative ratio of both the natural compound and PEG heavily affected the antiradical response, suggesting that chemical interactions in the established network were able, based on components' ratio, to differently mask and/or display the CGA moieties, commonly deemed relevant for antioxidant power exerting. Cell culture MTT assay was used to assess the biocompatibility of hybrid materials towards fibroblast NIH-3 T3 cells and neuroblastoma SH-SY5Y cells. Cells tested appeared differently responsive. In particular, a marked cell viability increase was observed when hybrids with low PEG amount (6%) and high CGA (15%) were directly exposed to fibroblast cells, whose mitochondrial redox activity was negatively affected by hybrid synthesized using the highest organic component rate (both PEG and CGA). Cell viability and morphology of human neuroblastoma SH-SY5Y cells were broadly compromised regardless of organic/inorganic starting materials ratio, suggesting the ability of hybrids to exert pro-oxidant effect towards tumour cells and to selectively interfere with their growth. The hybrids, able to elicit cleverly anti- or proliferative effects, were also shown to be bioactive. In fact, a biologically active hydroxyapatite layer was observed to be formed on the surface of the smart synthesized materials. This feature, which makes them a valuable bonding interface with tissues, opens new scenario aiming at further investigating the employment of natural phenol compounds in versatile sol-gel synthesis routes., (Copyright © 2019. Published by Elsevier B.V.)

Food-waste is produced throughout all the food supply chain, with a large part already achieved at farm level. In fact, fruits and vegetables, which do not satisfy aesthetic demands, cannot be marketed, but their recovery could favour their valorisation for the obtainment of highly qualified goods. In this context, faulty zucchini fruits (cultivar 'Lungo Fiorentino'), intended for disposal, were rescued as effective, inexpensive and bio-sustainable source for cosmeceutical purposes. Zucchini fruits underwent extraction and fractionation to obtain ZLF-O and ZLF-A extracts, which were chemically characterized by UHPLC-HRMS. ZLF-A extract, rich in flavonols and flavones, scavenged massively DPPH • and ABTS •+ , and was not cytotoxic at doses up to 200 μ g/mL. Thus, ZLF-A was incorporated into a base cream formula. Zucchini-based emulsion was deeply screened for its antiradical properties and cytotoxicity towards human keratinocytes and fibroblasts. ZLF-A-enriched cream, whose chemical stability was assessed over time and mimicking different storage conditions, was further tested on reconstructed epidermis disks (Episkin TM ). The recovery of valuable chemical substances from zucchini agro-food waste, complying with the principles of valorisation and sustainable development, can represent a new market force for local farmers. Data acquired were eager to convey a suitable reuse of nutraceuticals rich zucchini waste.

The diversity in phenols and polyphenols of stevia leaf has been simplified applying sequential fractionation techniques on its ethanol extract through ultrasound assisted maceration. Two of the fractions obtained by reverse-phase column chromatography resulted differently active in an extensive antioxidant and cytotoxic screening. Both fractions were chemically profiled by ultra-performance liquid chromatography (UHPLC) coupled with electrospray ionization (ESI) quadrupole/time-of-flight (QqTOF) mass spectrometry (MS). One of the fractions was composed mainly of chlorogenic acids and flavonol triglycosides, whereas the other was rich in flavonoids mono- and diglycosides and in their hydroxycinnamoyl derivatives. Among the fifty compounds identified, non-phenol metabolites, such as benzyl primeveroside and roseoside, as well as a lignan polyphenol (5'), are reported for the first time as constituents of the Stevia leaf., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The formation of pro-oxidant species after implantation of biomaterials could be responsible for the failure of the implant itself, because of oxidative stress-induced damage. In this work, the SiO₂/polyethylene glycol (PEG)/chlorogenic acid (CGA) hybrids synthesized by the sol⁻gel method with 50 wt% of the polymer and different amounts of CGA (5, 10, 15 and 20 wt%) were studied. The hybrids soaked in simulated body fluid (SBF) showed the formation of hydroxyapatite layers on their surface, suggesting that the hybrids are bioactive. Their radical scavenging capacity towards DPPH · and ABTS ·+ (2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), evaluated at three different doses (0.5, 1 and 2 mg), showed probe- and dose-dependent behavior. In addition, the antioxidant properties of CGA were not affected by the presence of high amounts of the polymer. The in vitro biocompatibility in three cell lines (NIH 3T3, HaCaT and SH-SY5Y) was assessed by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apart from SH-SY5Y, the cell viability-expressed as mitochondrial redox activity percentage of cells directly exposed to powders-and morphology was not affected, suggesting that the hybrids have the ability to interfere and act selectively against tumor cells. The antibacterial properties of the different materials against Escherichia coli and Enterococcus faecalis were affected by different amounts of the natural antioxidant component.

Lactobacillus plantarum is one of the most predominant species in the human gut microbiota of healthy individuals. We have previously characterized some probiotic features of L. plantarum LM3, as the high resistance to different stress, the binding ability toward some extracellular matrix proteins and plasminogen and the immunomodulatory role of the surface expressed adhesin EnoA1. We have also identified the flmA , flmB and flmC genes, coding for putative proteins named FlmA, FlmB and FlmC, whose null mutations partially impaired biofilm development; the L. plantarum LM3⁻6 strain, carrying a deletion in flmC , showed a high rate of autolysis, supporting the hypothesis that FlmC might be involved in cell wall integrity. Here, we report the in-silico characterization of ΔTM-FlmC, a portion of the FlmC protein. The protein has been also expressed, purified and characterized by means of CD spectroscopy, ICP-mass and UHPLC-HRMS. The obtained experimental data validated the predicted model unveiling also the presence of a bound lipid molecule and of a Mg(II) ion. Overall, we provide strong evidences that ΔTM-FlmC belongs to the LytR-CpsA-Psr (LCP) family of domains and is involved in cell envelope biogenesis.

The current cancer treatment scenario lacks drugs acting as both radiosensitizer and radioprotector agents. In this context, the radiomodulatory properties exerted by an aqueous extract from the fruits of the Italian Prunus avium cv. Della Recca (PaDRw) were investigated. The extract, obtained through an environmentally-friendly ultrasound-assisted extraction, seemed to act as a radioprotector at lower tested doses (25 and 50 μg mL -1 ) and a radiosensitizer at 400 and 500 μg mL -1 dose levels towards the neuroblastoma SH-SY5Y cell line, irradiated with four graded X-ray doses (0, 0.5, 2, and 4 Gy). The fractionation of PaDRw by Amberlite XAD-4 non-ionic polymeric resin, coupled to LC-UV-MS/MS techniques, proved to be efficient also in the disclosure of lower constituents. About 63% of the whole PaDRw extract was constituted of hexitol, followed by fructose (∼22.8%) and glucose (∼10.7%). Chlorogenic acids and flavonoids, which accounted only for ∼2.2%, were hypothesized to be the main actors in PaDRw-induced radiomodulation.