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• Pecorello and Mantonico pomaces represent a useful source of bioactive compounds. • Calabrian white grape pomaces were firstly investigated for their vasoactive properties. • The effects of extracts were analyzed in in vitro experiments on rat aorta rings. • Pecorello appeared more efficacious than Mantonico as a vasorelaxant extract. The valorisation of agrochemical wastes has become a low cost and sustainable tendency for the development of functional food. In particular, these enriched products seem to be enjoyable tools to treat metabolic disorders. In this field, Calabrian autochthonous white grape pomaces (Mantonico and Pecorello cultivar) were firstly investigated for their vasoactive properties. Skins and seeds were extracted and characterized by NMR spectroscopy, revealig the presence of numerous vasoactive compounds. The effects of extracts were analyzed in in vitro experiments on rat aorta rings (with and without endothelium), contracted by phenylephrine or KCl. Seeds extracts showed, differently from skins, an appreciable endothelium-dependent, eNOS-mediated vasodilation in the range 1–100 µg/mL. From a food market point of view, all the extracts were enclosed into a pectin polymer matrix. In the same experimental conditions, the polymers demonstrated the persistance of vasodilator activity only for Pecorello seed extract, which presented the most rich chemical profile. [ABSTRACT FROM AUTHOR]

In this paper, the preliminary results of a study aimed to discriminate between the different species of lichens, from which orchil dyes originate, are presented. A multi-analytical approach has been used to analyze several species of lichens, in particular Roccella tinctoria DC, Lasallia pustulata L. and Ochrolechia tartarea L., in an attempt to identify distinguishing markers within different orchil mixtures. In the first part of the research, samples of yarns dyed with the different species, prepared in laboratory after the proper raw lichens treatment, have been subjected to SERS on fiber analyses. Hence an innovative ammonia protocol has been applied to all the specimens. Firstly, in order to evaluate the difference among the different species, HPTLC has been applied to the extracts of dyed yarns and the dye baths. All the spots present on the TLC plates have been analyzed through SERS (HPTLC-SERS), in order to obtain a SERS database of each single compound, fixed on the yarns. Then, HPTLC-MS and HPLC-MS experiments have been carried out, in order to deep into the identification of compounds corresponding to each spot. [ABSTRACT FROM AUTHOR]

Trifluoromethyl aldimines derived from α-amino esters have proven to be very good starting materials to obtain the title compounds. A Ag 2 O-catalyzed Mannich-type/cyclization cascade reaction starting from suitable α-isocyano acetates leads to enantiopure valuable trans -carboxylic trifluoromethyl substituted 2-imidazolines by a highly stereoselective addition without the need to add organocatalysts. [ABSTRACT FROM AUTHOR]

The phytochemical analysis on the leaves of a new population of Araucaria columnaris (G.Forst.) Hook. was reported. Seven compounds were identified i.e., 15-agathic acid methyl ester (1), ladanein (2), 7,4′,7″,4‴-tetra- O -methyl-robustaflavone (3), 3- O - trans - p -coumaroyl-quinic acid (4), 4- O - trans - p -coumaroyl-quinic acid (5), 5- O - trans - p -coumaroyl-quinic acid (6) and shikimic acid (7). Chromatographic and spectroscopic techniques were utilized for this. Their presence is important from the chemophenetic point of view, but further research is necessary to make final conclusions on this species. • The phytochemical analysis on the leaves of Araucaria columnaris was reported. • This study regards a new European population. • Seven compounds were successfully identified. • Four compounds are new for the family, two for the genus and one for the species. • The chemotaxonomic importance of these compounds was adequately discussed. [ABSTRACT FROM AUTHOR]

Aqueous extracts of roasted pistachio (Pistacia vera) from different geographic origin were analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy. Forty-eight water-soluble metabolites, classified in organic acids, amino acids, carbohydrates and miscellaneous metabolites, were identified by means of 1D and 2D NMR experiments, and twenty-eight of them were quantified. The different metabolite contents highlighted that pistachios from different regions have peculiar metabolic features that could be employed for quality control and to improve the requisites for protected or certified designation of origin regulations. For these purposes, multivariate statistic analysis (PCA and PLS-DA) was applied to the obtained metabolite profiles in order to assess the geographic origin of nuts from Aleppo (Syria), Sanliurfa (Turkey), Rafsanjan (Iran) and Bronte (Italy), and spontaneous clustering was observed. [ABSTRACT FROM AUTHOR]

Age-related dysbioses of intestinal microbiota and decline in the overall metabolic homeostasis are frequently found in the elderly. Probiotic supplementation may represent a way to prevent or reduce the senescence-associated metabolic disorders. The present study evaluated the metabolic impact of Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 supplementation in relation to age by analyzing urine and feces metabolic profiles using ¹H-nuclear magnetic resonance spectroscopy and multivariate analysis. Adult (3 mo old) and aged (16 mo old) mice received an oral supplementation of the 2 probiotics (1 x 109 colony-forming units/d each) or phosphate buffered saline (control) daily for 30 d. Urine and feces were collected for 48 h before the end of the study. Partial least squares-discriminant analysis showed that the urinary discriminant metabolites for the probiotic treatment included higher dimethylglycine in adult and aged mice, lower sarcosine and nicotinate in adult mice, higher N-methylnicotinamide in adult mice and lower N-methylnicotinamide in aged mice compared with their controls. These results indicate a probiotic-induced modulation of homocysteine and NAD metabolism pathways, which have important implications because these pathways are involved in essential cellular processes that can be altered in senescence. The probiotic supplementation also modified the fecal metabolic profiles, inducing in both adult and aged mice higher 4-hydroxyphenylacetate and lower xylose in treated mice compared with their control mice, whereas valerate was greater in treated adult mice and lower in treated aged mice compared with their controls. The ANOVA simultaneous component analysis on urinary and fecal metabolic profiling showed an age x treatment interaction (P < 0.05}, confirming the age-related modulation of the metabolic response to probiotic supplementation. The results suggest that L. acidophilus and B. lactis may prevent or reduce age-related metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Tansy daisy ( Tanacetum macrophyllum (Waldst. et Kit.) Schultz Bip., Asteraceae) is a perennial herb worldwide cultivated for ornamental and industrial purposes. Sometimes, this species is misidentified by herb collectors and botanists with its family mate Achillea grandifolia (white yarrow). In the present work, we have analysed the essential oil and ethanolic extract obtained from the aerial parts of tansy daisy cultivated in Italy and evaluated the biological activity in terms of cytotoxic, antioxidant and anticholinesterase activities. The essential oil was analysed by gas chromatographic and mass spectrometry (GC–MS) and showed oxygenated monoterpenes, namely camphor, linalool and 1,8-cineole, and sesquiterpenes, namely germacrene D and 10- epi -γ-eudesmol, as the major components. The ethanolic extract of aerial parts was subjected to chromatographic separation and this permitted the identification of 12 polar compounds belonging to five different classes of natural products, namely flavonoids (apigenin, cirsimaritin, apigenin-7- O -glucoside, apigenin-7- O -glucuronide, kaempferol-7- O -glucoside and kaempferol-7- O -glucuronide), dicaffeoylquinic derivatives (3,5-dicaffeoylquinic and 4,5-dicaffeoylquinic acids), caffeoylquinic acids (chlorogenic acid), free organic acids (shikimic and quinic acids) and glycosidic organic acids (4- O -β- d -glucopyranosyl-vanillic acid); among them apigenin and kaempferol derivatives were the most abundant. Finally, the essential oil from the leaves, containing high levels of germacrene D and 10- epi -γ-eudesmol, was highly effective against the proliferation of A375 (melanoma) and HCT116 (colon carcinoma) human tumor cells, showing IC 50 values of 9.2 and 8.5 μg/mL, respectively. On the other hand, the ethanolic extract scavenged the DPPH and ABTS + radicals, showing IC 50 of 32.7 and 37.2 μg/mL, respectively. The inhibitory properties of tansy daisy essential oils and ethanol extract on the acetylcholinesterase enzyme were also evaluated. These findings provided new insights into the phytochemistry of the species and its possible applications on an industrial level. [ABSTRACT FROM AUTHOR]

Abstract: Background: Resveratrol, a polyphenol found in plant products, has been shown to regulate many cellular processes and to display multiple protective and therapeutic effects. Several in vitro and in vivo studies have demonstrated the influence of resveratrol on multiple intracellular targets that may regulate metabolic homeostasis. Methods: We analysed the metabolic modifications induced by resveratrol treatment in a human hepatoblastoma line, HepG2 cells, using a 1H-NMR spectroscopy-based metabolomics approach that allows the simultaneous screening of multiple metabolic pathways. Results: Results demonstrated that cells cultured in the presence or absence of resveratrol displayed different metabolic profiles: the treatment induced a decreased utilisation of glucose and amino acids for purposes of energy production and synthesis associated to a decreased release of lactate in the culture medium and an increase in succinate utilisation. At the same time, resveratrol treatment slowed the cell cycle in the S phase without inducing apoptosis, and increased Sirt1 expression, also affecting its intracellular localisation. Conclusions: Our results show that the metabolomic analysis of the exometabolome of resveratrol-treated HepG2 cells indicates a metabolic switch from glucose and amino acid utilisation to fat utilisation for the production of energy, and seem in agreement with an effect mediated via AMPK- and Sirt1-activation. General significance: NMR-based metabolomics has been applied in a hepatocyte cell culture model in relation to resveratrol treatment; such an approach could be transferred to evaluate the effects of nutritional compounds with health impact. [Copyright &y& Elsevier]

Hepatitis C virus (HCV) infection induces a long-term inflammatory response and oxidative-stress in the liver microenvironment, leading to hepatic fibrosis and metabolic alterations. Direct-acting-antiviral-agents (DAAs) induce HCV-clearance, even though liver damage is only partially restored. In this context, understanding the impact of viral-eradication on liver metabolic activities could allow optimizing the metabolic care of the patient. The present prospective longitudinal study aims at characterizing the urinary metabolic profile of HCV-induced severe liver fibrosis and the metabolic changes induced by DAAs and HCV-clearance by nuclear magnetic resonance-based metabolomics. The urinary metabolic profile of 23 HCV males with severe liver fibrosis and 20 age-matched healthy-controls was analyzed by NMR-based-metabolomics before starting DAAs, at the end-of-therapy, after one and three months of follow-up. The urinary metabolic profile of patients with severe liver fibrosis was associated to pseudouridine, hypoxanthine, methylguanidine and dimethylamine, highlighting a profile related to oxidative damage, and to tyrosine and glutamine, related to a decreased breakdown of aromatic aminoacids and ammonia detoxification, respectively. 1-methylnicotinamide, a catabolic intermediate of nicotinamide-adenine-dinucleotide, was significantly increased in HCV-patients and restored after HCV-clearance, probably due to the reduced hepatic inflammation. 3-hydroxy-3-methylbutyrate, an intermediate of leucine-catabolism which was permanently restored after HCV-clearance, suggested an improvement of skeletal muscle protein synthesis. Finally, 3-hydroxyisobutyrate and 2,3-dihydroxy-2-methylbutyrate, intermediates of valine-catabolism, glycine and choline increased temporarily during therapy, resulting as potential biomarkers of DAAs systemic effects. [Display omitted] • Urinary metabotypes were related to liver fibrosis, HCV-clearance and DAA treatment. • Severe liver fibrosis urinary metabotype was evidenced despite HCV eradication. • 1-MNA decrease after HCV-clearance was associated to a reduced hepatic inflammation. • 3-HMB increase after HCV-clearance was associated to protein synthesis in muscles. • Transient modifications of amino acid metabolism were induced by DAA treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hydrophilic gold nanoparticles for melamine detection were prepared. • The melamine was successfully detected in the range 2.5−500 ppm. • The sensing method based on the melamine-induced aggregation of AuNPs. • The recognition process is mediated by electrostatic interactions. In the last years, intense efforts have been made in order to obtain colloidal-based systems capable of pointing out the presence of melamine in food samples. In this work, we reported about the recognition of melamine in aqueous solution, using gold nanoparticles stabilized with 3-mercapto-1-propanesulfonate (AuNPs-3MPS), with the aim of deepening how the recognition process works. AuNPs were synthesized using a wet chemical reduction method. The synthesized AuNPs-3MPS probe was fully characterized, before and after the recognition process, by both physicochemical (UV–vis, FT-IR, 1H-NMR, DLS and ζ-potential) and morphostructural techniques (AFM, HR-TEM). The chemical and electronic structure was also investigated by SR-XPS. The sensing method is based on the melamine-induced aggregation of AuNPs; the presence of melamine was successfully detected in the range of 2.5−500 ppm. The results achieved also demonstrate that negatively charged AuNPs-3MPS are potentially useful for determining melamine contents in aqueous solution. SR-XPS measurements allowed to understand interaction mechanism between the probe and the analyte. The presence of sulfonate groups allows a mutual interaction mediated by electrostatic bonds between nanoparticles surface thiols and positively charged amino groups of melamine molecules. [ABSTRACT FROM AUTHOR]

Abstract In this work, the fifth part of an ongoing phytochemical study on Wollemia nobilis was reported. The attention was now focused on the male reproduction organs of which the content in both primary and secondary metabolites was analyzed. Twenty compounds, belonging to seven different classes of natural compounds, were identified from the ethanolic extract by means of Column Chromatography and NMR and MS Spectroscopy. They all represent new compounds for the studied organ whereas some of them are also new constituents of the genus or even previously undescribed phytochemicals. Their presence was able to display a general overview of these organs from the phytochemical standpoint and to provide more elements in confirmation with the current botanical classification of the species. Moreover, they add a further experimental evidence of the tendency of this species to accumulate different metabolites in different organs. This characteristic as well as the occurrence of several compounds with added value, make this plant a possible candidate for large scale cultivation with extractive purposes to obtain useful phytochemicals for botanicals and pharmaceutical fields. Moreover, they offer the opportunity to develop an additional method of conservation and protection for this endangered and very rare species. Graphical abstract Unlabelled Image Highlights • Two new secondary metabolites were isolated and identified. • A differential accumulation of metabolites in the various organs was observed. • A possible sustainable source of added value phytochemicals was suggested. • The chemotaxonomy relevance of isolated compounds was discussed. [ABSTRACT FROM AUTHOR]

Abstract An undescribed labdane-like diterpene with a rare spiro-β-lactone function was identified from the ethanol extract of the male cones of the coniferous tree Wollemia nobilis. This spirolabdadienolide (IUPAC name: syn - ent -8(17),13-labdadien-19,18-olid-15-oic acid methyl ester; trivial name: wollemolide), was isolated by means of traditional and high performance chromatography techniques and structurally elucidated through NMR and MS. In addition, six further known metabolites were evidenced in the extract. Wollemolide, which may be considered an additional chemotaxonomic marker, and 4′- O -methyl-scutellarein, a simple flavonoid, had not been isolated in our previous phytochemical study on the same plant organ. This demonstrates how the molecular pattern of a plant species is in continuous movement and changes with the passing of time according to the climate of the year. Graphical abstract Image 1 Highlights • A reassessment of Wollemia nobilis male cones was carried out. • An undescribed syn - ent -labdadiene derivative was isolated. • A seasonal variability of metabolites was observed. • This is the first report on the presence of simple flavonoids in W. nobilis. • The chemosystematic relevance of isolated compounds was discussed. [ABSTRACT FROM AUTHOR]

Abstract The influence of Synthetic Organic Pigments in the degradation of Acrylem AC 33, a waterborne acrylic binder, after UVB-artificial exposure was furtherly investigated, extending the study to other pigments classes (anthraquinones, phthalocyanines, diketo-pyrrolo-pyrroles) in addition to previously studied azo-pigments. Together with Fourier Transform Infrared, both in Attenuated Reflectance and Transmission mode, and Nuclear Magnetic Resonance spectroscopies, Raman spectroscopy was also used to observe ageing processes that pigments are subjected to. Specific effects, relative to the presence of different pigments, have been observed also in this study; moreover, Raman spectroscopy highlighted photoinduced effects on some pigments, which could result useful in Cultural Heritage diagnostics, especially for street artworks. Highlights • Combination of NMR, FTIR and Raman spectroscopies to study UVB induced degradation phenomena. • Influence of carbonyl, phthalocyanines and diketo-pyrrolo-pyrrole pigments on UV degradation of acrylic binder. • Variations in Raman spectra of pigments deriving from UVB photodegradation. [ABSTRACT FROM AUTHOR]

The preparation and characterization of a novel linear d , l -octapeptide-poly(ethylene glycol) conjugate, formulated as biocompatible nanocarrier of hydrophobic drugs, was reported. The PEGylated d , l -octapeptide was designed to self-assemble in core-shell nanoparticles with rod-like morphology obtained by exploiting the self-assembling properties of linear peptides with regularly alternating enantiomeric sequences in tubular structures. The conformational properties of the conjugate and its self-assembling capability were assessed through dynamic light scattering, energy filtered-transmission electron microscopy, scanning electron microscopy, circular dichroism, fluorescence, and proton nuclear magnetic resonance spectroscopy. Furthermore, the upload in peptide-polymer nanoparticles of curcumin, adopted as model of hydrophobic drugs, was performed. In fact, despite accumulating evidence suggests that curcumin has different therapeutic activities, its use in medicine is limited to the very low water solubility, low bioavailability and chemical instability. This work addresses such drawbacks showing that nanoparticles obtained by For-( d -Phe- l -Cys(Acm)) 4 -NH-(CH 2 -CH 2 -O) 45 -CH 3 self-assembly are effective carriers for curcumin with high drug loading and sustained drug release. [ABSTRACT FROM AUTHOR]

Helichrysum stoechas (L.) Moench is one of the scientific names of everlasting flower, which has traditionally been used as an ornamental, medicinal and food plant. The aim of this study was to identify the main phytochemical constituents as well as to evaluate the potential of this plant in terms of antioxidant, antidiabetic and neuroprotective activities. The phytochemical analysis of the methanolic extract allowed for the identification of ten constituents mainly of phenolic nature and with chemosystematic relevance: two heterodimeric phloroglucinols, arzanol ( 1 ) and compound ( 3 ), one homodimeric α-pyrone, helipyrone ( 2 ), three phenolic acids, p -hydroxybenzoic ( 4 ), caffeic ( 5 ) and neochlorogenic ( 6 ) acids, one polymethoxylated and two glycosidic flavonoids, 5,7-dihydroxy-3,6,8-trimethoxyflavone ( 7 ), isoquercitrin ( 8 ) and quercetagetin-7- O -glucopyranoside ( 9 ) together with santinol B ( 10 ). Bioassays showed significant antioxidant and antiproliferative effects and for the first time the potential of Helichrysum stoechas to inhibit the MAO-A, AChE and TYR enzymes, as well as to exert anti-α-glucosidase and anti-dipeptidyl peptidase-4 activities. [ABSTRACT FROM AUTHOR]

Caralluma fimbriata Wall. is currently used as a “natural slimming” food supplement, likely due to its content in pregnane glycosides. In the present study, a commercially available Caralluma fimbriata extract (Slimaluma ® ; CFE, 100 mg/kg) has been evaluated for its ability to affect the ingestive behaviour in female rats, also with reference to the modulation of the brain neuropeptides NPY and ORX.The interference of CFE with α-amylase and lipase enzymes has been investigated in vitro , as possible peripheral mechanism of action. Also, the chemical composition of CFE has been assessed by NMR and spectrophotometric analysis. Results from in vivo study showed that CFE induced effects neither on blood parameters, nor on liver and gut histomorphology. Interestingly, a reduction in body weight gain with an increase in water intake and hypothalamic levels of NPY and ORX peptides were found. Phytochemical analysis, showed CFE contained about 12% of pregnane glycosides and 1.3% of polyphenols. Present results suggest possible effects of C. fimbriata on ingestive behaviour, likely mediated by central and peripheral mechanisms. [ABSTRACT FROM AUTHOR]

Olive oil mill wastewaters (OMW) cause serious environmental pollution problems due to their high level of production and specific chemical characteristics. An innovative disposal treatment and simultaneous valorization technology consists of using OMW as a no-cost substrate for mixed microbial culture (MMC)-based polyhydroxyalkanoates (PHAs) production process. Here, an MMC multi-stage process was developed in which after acidogenic fermentation, OMW was subjected to a solid liquid separation step by centrifugation. The resulting solid fraction was converted into methane through anaerobic digestion in order to recover energy for the process, whereas the liquid fraction was used as feedstock for both the biomass selection and the PHA accumulation step. Most of OMW soluble chemical oxygen demand (COD) content in the liquid fraction (approximately 70%) was removed in a sequencing batch reactor (SBR) obtaining a high PHA production (about 532 mgCOD, in the feast phase). In particular, the strategy to uncouple COD feed from nitrogen supply within the SBR cycle, along with the operation of a settling phase before the famine phase, allowed to enhance the selective pressure towards PHA-storing microorganisms. Polymer production significantly increased in the accumulation reactor up to approximately 2470 mgCOD/L. Finally, anaerobic digestion tests on the OMW solid fraction showed a relevant COD conversion into methane (up to 100%). [ABSTRACT FROM AUTHOR]

In this study, The behavior of Acrylem AC 33–a waterborne paint binder, chemically a ethyl acrylate-methyl methacrylate copolymer-after an UVB-artificial ageing was evaluated. In particular, it has been investigated its behavior in presence of three different azo-pigments – Pigment Red 9, Pigment Yellow 3 and Pigment Yellow 74-, in order to evaluate the effects of these pigments on photodegradation processes of the medium. For this aim, Fourier Transformed InfraRed, both in Attenuated Reflectance and transmission mode, and Nuclear Magnetic Resonance Spectroscopies were used. Thanks to this multianalytical approach, the chemical variations, both on the surface and on the bulk of the pictorial film, have been assessed and the degradation products of surfactant present in the binder were identified. Furthermore, specific effects of these synthetic organic pigments on the photodegradation of the matrix and its additives were observed. The information obtained from this study can be employed in the characterization of differential ageing phenomena in artworks, especially in case of outdoor exposition as it occurs in street-art conditions. [ABSTRACT FROM AUTHOR]

Teucrium polium L. is a species with ancient ethno-botanical uses for its anti-inflammatory action which is mainly due to the phenolics content. On the other side, the presence of neo -clerodanes, which exert hepatotoxic action, may explain why in recent years the medicinal uses of this species have drastically diminished. In this paper we report on the isolation of a new natural neo -clerodane diterpenoid, namely 20- O -acetyl-teucrasiatin ( 2 ), together with other twelve relevant compounds in the fields of chemotaxonomy and ethnomedicine. Nevertheless, the total absence of iridoids and in particular of the chemotaxonomic markers of the family and of the genus itself, may reveal an intraspecific variability of T. polium with different chemotypes which may contain or not iridoids. [ABSTRACT FROM AUTHOR]

Abstract: Background: Aging is characterized by derangements in multiple metabolic pathways that progressively constrict the homeostatic reserve (homeostenosis). The signature of metabolic alterations that accompany aging can be retrieved through the metabolomic profiling of biological fluids. Objective: To characterize the age-related changes in urinary and fecal metabolic profiles of BALB/c mice through a 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Methods: Young (n=19) and old (n=13) male BALB/c mice were fed ad libitum standard laboratory chow. Twenty four-hour feces and urine were collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. Results: An age-related metabolic phenotype was detected both in urine and feces. The metabolic signature of aging consisted of changes in levels of metabolites associated with amino acid metabolism, tricarboxylic acid cycle, tryptophan–nicotinamide adenine dinucleotide pathway, and host–microbiota metabolic axis. Conclusions: Our 1H NMR-based metabolomic approach was able to characterize the effect of age on urinary and fecal metabotypes. The implementation of this analytical strategy may increase our understanding of the metabolic alterations involved in the aging process and assist in the design of anti-aging interventions. [Copyright &y& Elsevier]

Abstract: Chiral racemic α-diimines, tested in aziridination reactions with NsONHCO2Et, for the first time led to the synthesis of (±)-bidiaziridines, stereoselectively derived from the corresponding meso (E-s-trans-E)-α-diimines. Moreover, a minor bidiaziridine isomer, probably a meso form that was lost under classical work-up conditions, can be obtained by adding water to the crude mixtures at the end of amination reactions. The results definitively prove that the imine aziridination by carbamates is a two-step domino process. The structures of the compounds were determined using 2D NMR on purified bidiaziridines. [Copyright &y& Elsevier]

Abstract: The aim of this study was to individuate, by bioassay-guided fractionation, promising antifungal fractions and/or constituents from Hypericum perforatum subsp. angustifolium in vitro roots. Treatments with chitosan, O-carboxymethylchitosan (CMC) and its derivatives were used to improve xanthone production in the roots. The bioassay-guided fractionation of CMC-treated roots led to the individuation of an ethyl acetate fraction, containing the highest amount of xanthones (6.8%) and showing the best antifungal activity with minimal inhibitory concentration (MIC) values of 53.82, 14.18, and 36.52 μg/ml, against Candida spp., Cryptococcus neoformans and dermatophytes, respectively. From this fraction the prenylated xanthone, biyouxanthone D has been isolated and represented the 44.59% of all xanthones detected. For the first time in the present paper biyouxanthone D has been found in H. perforatum roots and tested against C. neoformans, dermatophytes, and Candida species. The xanthone showed the greatest antifungal activity against C. neoformans and dermatophytes, with MIC values of 20.16, 22.63 μg/ml. In conclusion, the results obtained in the present study demonstrated that CMC-treated Hpa in vitro root extracts represent a tool for the obtainment of promising candidates for further pharmacological and clinical studies. [Copyright &y& Elsevier]

The execution of many genetic programs, influenced by environmental conditions, is epigenetically controlled. Thus, small molecules of the intermediate metabolism being precursors of most of nutrition-deriving epigenetic modifications, sense the cell surrounding environment. Here we describe histone H4K16 acetylation distribution in S. cerevisiae nhp6ab mutant, using ChIP-seq analysis; its transcription profile by RNA-seq and its metabolic features by studying the metabolome. We then intersected these three -omic approaches to unveil common crosspoints (if any). In the nhp6ab mutant, the glucose metabolism is switched to pathways leading to Acetyl-CoA synthesis. These enhanced pathways could lead to histone hyperacetylation altering RNA transcription, particularly of those metabolic genes that maintain high Acetyl-CoA availability. Thus, the absence of chromatin regulators like Nhp6 A and B, interferes with a regulative circular mechanism where histone modification, transcription and metabolism influence each other and contribute to clarify the more general phenomenon in which gene regulation feeds metabolic alterations on epigenetic basis. This study allowed us to identify, in these two factors, a common element of regulation in metabolism and chromatin acetylation state that could represent a powerful tool to find out relationships existing between metabolism and gene expression in more complex systems. Unlabelled Image • nhp6ab Strain shows globally hyperacetylated histones particularly at H4K16. • Metabolomic analysis shows altered glucose metabolism in the nhp6ab mutant. • Transcriptome and H4K16 acetylome are altered in the nhp6ab mutant. • NHP6A/B Affect a circuit involving histone acetylation, metabolism and transcription. [ABSTRACT FROM AUTHOR]