Over the past few years, nutraceuticals have gained substantial attention due to the health-promoting and disease-preventing functions behind their nutritional value. The global prevalence of nutraceuticals is reflected in the increasing number of commercially available nutraceuticals and their wide range of applications. Therefore, a unique opportunity emerges for their further exploration using innovative, reliable, accurate, low cost, and high hit rate methods to design and develop next generation nutraceuticals. Towards this direction, computational techniques constitute an influential trend for academic and industrial research, providing not only the chemical tools necessary for further mechanism characterization but also the starting point for the development of novel nutraceuticals. In the present review, an overview of nutraceuticals is discussed, underscoring the crucial role of chemoinformatic platforms, chemolibraries, and in silico techniques, as well as their perspectives in the development of novel nutraceuticals. This review also aims to record the latest advances and challenges in the area of nanonutraceuticals, an innovative field that capitalizes on the assets of nanotechnology for the encapsulation of bioactive components in order to improve their release profile and therapeutic efficacy.

A variety of bioactive compounds, constituents of edible mushrooms, in particular β-glucans, i.e., a group of β-d-glucose polysaccharides abundant in the fungal cell walls, have been linked to immunomodulating, anticancer and prebiotic activities. The aim of the study was the investigation of the genoprotective effects of edible mushrooms produced by Pleurotus eryngii, Pleurotus ostreatus and Cyclocybe cylindracea (Basidiomycota). Mushrooms from selected strains of the species mentioned above were fermented in vitro using faecal inocula from healthy volunteers. The cytotoxic and anti-genotoxic properties of the fermentation supernatants (FSs) were investigated in Caco-2 human colon adenocarcinoma cells. The FSs were cytotoxic in a dose-dependent manner. Non-cytotoxic concentrations were used for the genotoxicity studies, which revealed that mushrooms’ FSs have the ability to protect Caco-2 cells against tert-butyl hydroperoxide (t-BOOH), a known genotoxic agent. Their global metabolic profiling was assessed by ¹H-NMR spectroscopy. A total of 37 metabolites were identified with the use of two-dimensional (2D) homo- and hetero-nuclear NMR experiments. Multivariate data analysis monitored the metabolic variability of gut microbiota and probed to biomarkers potentially associated with the health-promoting effects of edible mushrooms.

Edible mushrooms contain biologically active compounds with antioxidant, antimicrobial, immunomodulatory and anticancer properties. The link between their anticancer and immunomodulatory properties with their possible prebiotic activity on gut micro-organisms has been the subject of intense research over the last decade. Lyophilized Pleurotus eryngii (PE) mushrooms, selected due to their strong lactogenic effect and anti-genotoxic, immunomodulatory properties, underwent in vitro static batch fermentation for 24 h by fecal microbiota from eight elderly apparently healthy volunteers (>65 years old). The fermentation-induced changes in fecal microbiota communities were examined using Next Generation Sequencing of the hypervariable regions of the 16S rRNA gene. Primary processing and analysis were conducted using the Ion Reporter Suite. Changes in the global metabolic profile were assessed by ¹H NMR spectroscopy, and metabolites were assigned by 2D NMR spectroscopy and the MetaboMiner platform. PLS-DA analysis of both metataxonomic and metabolomic data showed a significant cluster separation of PE fermented samples relative to controls. DEseq2 analysis showed that the abundance of families such as Lactobacillaceae and Bifidobacteriaceae were increased in PE samples. Accordingly, in metabolomics, more than twenty metabolites including SCFAs, essential amino acids, and neurotransmitters discriminate PE samples from the respective controls, further validating the metataxonomic findings.

Coffee is one of the most widely consumed beverages worldwide due to its sensory and potential health-related properties. In the present comparative study, a preparation known as Greek or Turkish coffee, made with different types/varieties of coffee, has been investigated for its physicochemical attributes (i.e., color), antioxidant/antiradical properties, phytochemical profile, and potential biological activities by combining high-throughput analytical techniques, such as infrared spectroscopy (ATR-FTIR), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and in silico methodologies. The results of the current study revealed that roasting degree emerged as the most critical factor affecting these parameters. In particular, the L* color parameter and total phenolic content were higher in light-roasted coffees, while decaffeinated coffees contained more phenolics. The ATR-FTIR pinpointed caffeine, chlorogenic acid, diterpenes, and quinic esters as characteristic compounds in the studied coffees, while the LC-MS/MS analysis elucidated various tentative phytochemicals (i.e., phenolic acids, diterpenes, hydroxycinnamate, and fatty acids derivatives). Among them, chlorogenic and coumaric acids showed promising activity against human acetylcholinesterase and alpha-glucosidase enzymes based on molecular docking studies. Therefore, the outcomes of the current study provide a comprehensive overview of this kind of coffee preparation in terms of color parameters, antioxidant, antiradical and phytochemical profiling, as well as its putative bioactivity.

In the current market, there is a growing interest in traditional herbal nutraceuticals. Therefore, herbal formulations have re-emerged as products with sought-after nutraceutical and disease-preventing properties. The health-promoting effects of herbal bioactives are attributed to the active phytoconstituents of these plants. Thus, the aim of the present study was to evaluate the putative nutraceutical effectiveness of the preparations of ten herbs (chamomile, purple coneflower, lemon verbena, pennyroyal, spearmint, oregano, marjoram, headed savory, sea buckthorn, and St. John’s wort) by combining in silico techniques and LC-MS/MS analysis. The binding potential of the selected phenolic compounds, according to literature and web databases, was investigated by using molecular target prediction tools. Aldose reductase (AR), an enzyme of polyol pathway which is related to hyperglycemic-induced pathologies, emerged as the most promising molecular target. The molecular docking results showed that rosmarinic acid, caftaric acid, naringenin, and quercetin presented the highest binding affinity. In a further step, the phytochemical profile of the examined infusions, obtained by LC-MS/MS analysis, revealed that the abovementioned compounds were present, mainly in the herbs of the Lamiaceae family, designating headed savory as the herbal infusion with possible significant inhibitory activity against AR.

Nowadays, the explosion of knowledge in the field of epigenetics has revealed new pathways toward the treatment of multifactorial diseases, rendering the key players of the epigenetic machinery the focus of today’s pharmaceutical landscape. Among epigenetic enzymes, DNA methyltransferases (DNMTs) are first studied as inhibition targets for cancer treatment. The increasing clinical interest in DNMTs has led to advanced experimental and computational strategies in the search for novel DNMT inhibitors. Considering the importance of epigenetic targets as a novel and promising pharmaceutical trend, the present study attempted to discover novel inhibitors of natural origin against DNMTs using a combination of structure and ligand-based computational approaches. Particularly, a pharmacophore-based virtual screening was performed, followed by molecular docking and molecular dynamics simulations in order to establish an accurate and robust selection methodology. Our screening protocol prioritized five natural-derived compounds, derivatives of coumarins, flavones, chalcones, benzoic acids, and phenazine, bearing completely diverse chemical scaffolds from FDA-approved “Epi-drugs”. Their total DNMT inhibitory activity was evaluated, revealing promising results for the derived hits with an inhibitory activity ranging within 30–45% at 100 µM of the tested compounds.