Olive Tree in Circular Economy as a Source of Secondary Metabolites Active for Human and Animal Health Beyond Oxidative Stress and Inflammation

Abstract Extra-virgin olive oil (EVOO) contains many bioactive compounds with multiple biological activities that make it one of the most important functional foods. Both the constituents of the lipid fraction and that of the unsaponifiable fraction show a clear action in reducing oxidative stress by acting on various body components, at concentrations established by the European Food Safety Authority’s claims. In addition to the main product obtained by the mechanical pressing of the fruit, i.e., the EVOO, the residual by-products of the process also contain significant amounts of antioxidant molecules, thus potentially making the Olea europea L. an excellent example of the circular economy. In fact, the olive mill wastewaters, the leaves, the pomace, and the pits discharged from the EVOO production process are partially recycled in the nutraceutical and cosmeceutical fields also because of their antioxidant effect. This work presents an overview of the biological activities of these by-products, as shown by in vitro and in vivo assays, and also from clinical trials, as well as their main formulations currently available on the market

Novel insights in health-promoting properties of sweet cherries

n/

Microwave-Assisted Extraction of Bioactive Compounds from Lentil Wastes: Antioxidant Activity Evaluation and Metabolomic Characterization

The recovery of industrial by-products is part of the zero-waste circular economy. Lentil seed coats are generally considered to be a waste by-product. However, this low-value by-product is rich in bioactive compounds and may be considered an eco-friendly source of health-promoting phytochemicals. For the first time, a sustainable microwave-assisted extraction technique was applied, and a solvent screening was carried out to enhance the bioactive compound content and the antioxidant activity of green and red lentil hull extracts. With respect to green lentil hull extracts that were obtained with different solvents, the aqueous extract of the red lentil seed coats showed the highest total phenolic and total flavonoid content (TPC = 28.3 ± 0.1 mg GAE/g dry weight, TFC = 1.89 ± 0.01 mg CE/100 mg dry weight, respectively), as well as the highest antioxidant activity, both in terms of the free radical scavenging activity (ABTS, 39.06 ± 0.73 mg TE/g dry weight; DPPH, IC50 = 0.39 μg/mL) and the protection of the neuroblastoma cell line (SH-SY5Y, IC50 = 10.1 ± 0.6 μg/mL), the latter of which has never been investigated so far. Furthermore, a metabolite discovery analysis was for the first time performed on the aqueous extracts of both cultivars using an HPLC separation which was coupled with an Orbitrap-based high-Resolution Mass Spectrometry technique

Totarol content and cytotoxicity varies significantly in different types of propolis

Propolis is a complex honeybee product deposited in the beehives, where it protects the hive and its occupants from microbial infection. Propolis has several reported medical applications in view of its numerous bioactive properties. The water insoluble fraction of crude Maltese honeybee propolis was extracted in methanol. Analysis by gas chromatography – mass spectrometry (GC-MS) showed the diterpenoid totarol to be the predominant constituent in all samples. The evaporated methanol residue was dissolved in dimethyl sulphoxide (DMSO) and used for cytotoxicity testing on human cancer cell lines using standard 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assays. Results obtained show that the propolis collected from Malta has cytotoxic activity in cancer cells in vitro. However, propolis collected from different sites, only a few miles apart and at different times of the year, showed marked variations in the cytotoxicity, which correlated clearly with totarol content. This reflects the differences in the species of plants, on which the bees had foraged and indicates the importance of collection site and season of collection on the bioactivity of propolis products.peer-reviewe

Increased sodium channel use-dependent inhibition by a new potent analogue of tocainide greatly enhances in vivo antimyotonic activity

Although the sodium channel blocker, mexiletine, is the first choice drug in myotonia, some myotonic patients remain unsatisfied due to contraindications, lack of tolerability, or incomplete response. More therapeutic options are thus needed for myotonic patients, which require clinical trials based on solid preclinical data. In previous structure-activity relationship studies, we identified two newly-synthesized derivatives of tocainide, To040 and To042, with greatly enhanced potency and use-dependent behavior in inhibiting sodium currents in frog skeletal muscle fibers. The current study was performed to verify their potential as antimyotonic agents. Patch-clamp experiments show that both compounds, especially To042, are greatly more potent and use-dependent blockers of human skeletal muscle hNav1.4 channels compared to tocainide and mexiletine. Reduced effects on F1586C hNav1.4 mutant suggest that the compounds bind to the local anesthetic receptor, but that the increased hindrance and lipophilia of the N-substituent may further strengthen drug-receptor interaction and use-dependence. Compared to mexiletine, To042 was 120 times more potent to block hNav1.4 channels in a myotonia-like cellular condition and 100 times more potent to improve muscle stiffness in vivo in a previously-validated rat model of myotonia. To explore toxicological profile, To042 was tested on hERG potassium currents, motor coordination using rotarod, and C2C12 cell line for cytotoxicity. All these experiments suggest a satisfactory therapeutic index for To042. This study shows that, owing to a huge use-dependent block of sodium channels, To042 is a promising candidate drug for myotonia and possibly other membrane excitability disorders, warranting further preclinical and human studies

2D- and 3D-QSAR of tocainide and mexiletine analogues acting as Na(v)1.4 channel blockers

Enantiomeric forms of Tocainide, Mexiletine, and structurally related local anaesthetic compounds, were analyzed with respect to their potency in blocking Nav1.4 channel. Structure–activity relationships based on in vitro pharmacological assays, suggested that an increase in terms of lipophilicity and/or molecular surface as well as the presence of specific polar spacers might be determinant for receptor interactions. QSAR and pharmacophore models were then used to support at 3D level this hypothesisEnantiomeric forms of Tocainide. Mexiletine, and structurally related local anaesthetic compounds, were analyzed with respect to their potency in blocking Na(v)1.4 channel. Structure-activity relationships based on in vitro pharmacological assays, suggested that an increase in terms of lipophilicity and/or molecular surface as well as the presence of specific polar spacers might be determinant for receptor interactions. QSAR and pharmacophore models were then used to support at 3D level this hypothesis. (C) 2008 Elsevier Masson SAS. All rights reserved

Processing of Carob Kernels to Syrup by Ultrasound-Assisted Extraction

Carob syrup is one of the most important carob products, which can have applications in pastry and confectionery, as a fruit preservative, but also in the pharmaceutical field because of the antimicrobial activity due to its polyphenol content. Carob syrup is traditionally made through a very time-consuming process, involving solid–liquid extraction in boiling water and concentration at a high temperature (>100 °C), which potentially causes the degradation of the active compounds (i.e., procyanidins or flavonol glycosides). Therefore, in this work, an alternative and less drastic method based on ultrasound technology was proposed to produce carob syrup. Processing conditions (i.e., time, temperature, and liquid–solid ratio) influencing the extraction of total soluble solids (TSS) and total phenolic compounds (TPC) were optimized using a central composite design coupled to response surface methodology. Reliable mathematical models allowed us to predict the highest TSS (24 ± 2 °Brix) and TPC (1.7 ± 0.5 mg/mL) values that could be obtained at 15 min, 35 °C, and 2 mL/g. Finally, a different HPLC-DAD phenolic pattern was determined between syrups produced by traditional and ultrasound methods; epicatechin, 4-hydroxycoumaric acid, and ferulic acid were more concentrated in the former, while procyanidin B2, myricitrin, and quercitrin were prevalent in the latter one

Ultrasound Assisted Extraction of Polyphenols from Ripe Carob Pods (Ceratonia siliqua L.): Combined Designs for Screening and Optimizing the Processing Parameters

Carob pulp has recently received great attention due to its considerable content of polyphenols having a wide range of health promoting effects. In this work, ultrasound assisted extraction was optimized sequentially using a screening Plackett–Burman design and non-standard central composite design coupled to response surface methodology and desirability function statistical tools, to find the best conditions for the extraction of nine polyphenols from carob pods. The gathered mathematical models showed that the highest significant factors influencing the extraction of all compounds were solid–solvent ratio, solvent concentration, and particle size, with the optimal results obtained at values of 0.2 g/mL, 40% ethanol, and 0.3 mm, respectively. Extraction temperature, time, sonication power, and frequency were set at 35 °C, 15 min, 100 W, and 37 kHz, respectively. These parameters help to reduce energy costs and to obtain the best possible extraction of polyphenols

Overview of the Polyphenols in Salicornia: From Recovery to Health-Promoting Effect

Nowadays, there has been considerable attention paid toward the recovery of waste plant matrices as possible sources of functional compounds with healthy properties. In this regard, we focus our attention on Salicornia, a halophyte plant that grows abundantly on the coasts of the Mediterranean area. Salicornia is used not only as a seasoned vegetable but also in traditional medicine for its beneficial effects in protecting against diseases such as obesity, diabetes, and cancer. In numerous research studies, Salicornia consumption has been highly suggested due to its high level of bioactive molecules, among which, polyphenols are prevalent. The antioxidant and antiradical activity of polyphenols makes Salicornia a functional food candidate with potential beneficial activities for human health. Therefore, this review provides specific and compiled information for optimizing and developing new extraction processes for the recovery of bioactive compounds from Salicornia; focusing particular attention on polyphenols and their health benefits