Chemoinformatic Database Building and in Silico Hit-Identification of Potential Multi-Targeting Bioactive Compounds Extracted from Mushroom Species.

Mushrooms are widely-consumed fungi which contain natural compounds that can be used both for their nutritive and medicinal properties, i.e., taking advantage of their antimicrobial, antiviral, antitumor, anti-allergic, immunomodulation, anti-inflammatory, anti-atherogenic, hypoglycemic, hepatoprotective and antioxidant effects. Currently, scientific interest in natural compounds extracted from the fungal species is increasing because these compounds are also known to have pharmacological/biological activity. Unfortunately, however, their mechanisms of action are often unknown, not well understood or have not been investigated in their entirety. Given the poly-pharmacological properties of bioactive fungal compounds, it was decided to carry out a multi-targeted approach to predict possible interactions occurring among bioactive natural fungal extracts and several macromolecular targets that are therapeutically interesting, i.e., proteins, enzymes and nucleic acids. A chemical database of compounds extracted from both edible and no-edible mushrooms was created. This database was virtually screened against 43 macromolecular targets downloaded from the Protein Data Bank website. The aim of this work is to provide a molecular description of the main interactions involving ligand/multi-target recognition in order to understand the polypharmacological profile of the most interesting fungal extracts and to suggest a design strategy of new multi-target agents.

Eriocitrin and Apigenin as New Carbonic Anhydrase VA Inhibitors from a Virtual Screening of Calabrian Natural Products.

In this work, we performed a structure-based virtual screening against five carbonic anhydrase isoforms using, as a ligand library, natural components of Citrus bergamia (Bergamot) and Allium cepa var. Tropea (red onion) sources, which are some typical Calabrian products. The most relevant Bergamot and red onion components, identified as potentially new hits by means of the computational work, were submitted to in vitro tests in order to confirm the ability to exert the predicted biological activity. Apigenin and eriocitrin were identified as new potent inhibitors of human carbonic anhydrase VA isozyme.

(1)H-NMR-based metabolomic analysis of the effect of moderate wine consumption on subjects with cardiovascular risk factors.

Moderate wine consumption is associated with health-promoting activities. An H-NMR-based metabolomic approach was used to identify urinary metabolomic differences of moderate wine intake in the setting of a prospective, randomized, crossover, and controlled trial. Sixty-one male volunteers with high cardiovascular risk factors followed three dietary interventions (28 days): dealcoholized red wine (RWD) (272mL/day, polyphenol control), alcoholized red wine (RWA) (272mL/day) and gin (GIN) (100mL/day, alcohol control). After each period, 24-h urine samples were collected and analyzed by (1) H-NMR. According to the results of a one-way ANOVA, significant markers were grouped in four categories: alcohol-related markers (ethanol); gin-related markers; wine-related markers; and gut microbiota markers (hippurate and 4-hydroxphenylacetic acid). Wine metabolites were classified into two groups; first, metabolites of food metabolome: tartrate (RWA and RWD), ethanol, and mannitol (RWA); and second, biomarkers that relates to endogenous modifications after wine consumption, comprising branched-chain amino acid (BCAA) metabolite (3-methyl-oxovalerate). Additionally, a possible interaction between alcohol and gut-related biomarkers has been identified. To our knowledge, this is the first time that this approach has been applied in a nutritional intervention with red wine. The results show the capacity of this approach to obtain a comprehensive metabolome picture including food metabolome and endogenous biomarkers of moderate wine intake.

Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer's disease.

Red blood cells (RBCs) are characterized by a remarkable elasticity, which allows them to undergo very large deformation when passing through small vessels and capillaries. This extreme deformability is altered in various clinical conditions, suggesting that the analysis of red blood cell (RBC) mechanics has potential applications in the search for non-invasive and cost-effective blood biomarkers. Here, we provide a comparative study of the mechanical response of RBCs in patients with Alzheimer's disease (AD) and healthy subjects. For this purpose, RBC viscoelastic response was investigated using atomic force microscopy (AFM) in the force spectroscopy mode. Two types of analyses were performed: (i) a conventional analysis of AFM force-distance (FD) curves, which allowed us to retrieve the apparent Young's modulus, E; and (ii) a more in-depth analysis of time-dependent relaxation curves in the framework of the standard linear solid (SLS) model, which allowed us to estimate cell viscosity and elasticity, independently. Our data demonstrate that, while conventional analysis of AFM FD curves fails in distinguishing the two groups, the mechanical parameters obtained with the SLS model show a very good classification ability. The diagnostic performance of mechanical parameters was assessed using receiving operator characteristic (ROC) curves, showing very large areas under the curves (AUC) for selected biomarkers (AUC > 0.9). Taken all together, the data presented here demonstrate that RBC mechanics are significantly altered in AD, also highlighting the key role played by viscous forces. These RBC abnormalities in AD, which include both a modified elasticity and viscosity, could be considered a potential source of plasmatic biomarkers in the field of liquid biopsy to be used in combination with more established indicators of the pathology.

Kaempferol as Selective Human MAO-A Inhibitor: Analytical Detection in Calabrian Red Wines, Biological and Molecular Modeling Studies.

The purpose of this work was to determine the kaempferol content in three red wines of Calabria, a southern Italian region with a great number of certified food products. Considering that wine cultivar, climate, and soil influence the qualitative and quantitative composition in flavonoids of Vitis vinifera L. berries, the three analyzed samples were taken from the 2013 vintage. Moreover, the Gaglioppo samples, with assigned Controlled Origin Denomination (DOC), were also investigated in the production of years 2008, 2010, and 2011. In addition to the analysis of kaempferol, which is present in higher concentration than in other Italian wines, in vitro assays were performed to evaluate, for the first time, the inhibition of the human monoamine oxidases (hMAO-A and hMAO-B). Molecular recognition studies were also carried out to provide insight into the binding mode of kaempferol and selectivity of inhibition of the hMAO-A isoform.

New insights into the biological properties of Crocus sativus L.: chemical modifications, human monoamine oxidases inhibition and molecular modeling studies.

Although there are clinical trials and in vivo studies in literature regarding the anxiolytic and antidepressant activities of the components of Crocus sativus L., their effects on the human monoamine oxidases (hMAO-A and hMAO-B), enzymes which are involved in mental disorders and neurodegenerative diseases, have not yet been investigated. We have thus examined the hMAO inhibitory activities of crocin and safranal (the most important active principles in saffron) and, subsequently, designed a series of safranal derivatives to evaluate which chemical modifications confer enhanced inhibition of the hMAO isoforms. Docking simulations were performed in order to identify key molecular recognitions of these inhibitors with both isoforms of hMAO. In this regard, different mechanisms of action were revealed. This study concludes that safranal and crocin represent useful leads for the discovery of novel hMAO inhibitors for the clinical management of psychiatric and neurodegenerative disorders.