From oil to microparticulate by prilling technique: Production of polynucleate alginate beads loading Serenoa Repens oil as intestinal delivery systems.

Natural oils that are rich in biologically active polyunsaturated fatty acids have many health benefits but have insufficient bioavailability and may oxidize in the gastrointestinal tract. For these reasons and to improve the handling as well, the possibility of incorporating a natural oil, extracted from Serenoa Repens fruits (SR-oil), in alginate-based beads was investigated. SR-oil has been used from centuries in both traditional and modern medicine for various nutraceutical or therapeutic purposes such as, in both sexes, as a general tonic, for genitourinary problems, to increase sexual vigor, as a diuretic or to treat in male lower urinary tract symptoms and benign prostatic hyperplasia. In this study, alginate-based beads prepared by vibration technology, also known as prilling technique, were explored as SR-oil delivery systems. Twenty-seven different formulations (F1-F27) were produced starting from stable emulsions for the period of the production. The formulations having spheroid shape (sfericity factor <0.07), high formulation yield (>90%) and high encapsulation efficiency (EE% > 80) were selected for further characterizations. Gas chromatographic analysis revealed a high loading of lauric acid as principal component of SR-oil allowing to calculate the content of total fatty acids (>50%) into the beads. Swelling behavior and release features were also studied at different pH values. The swelling of the beads and their SR-oil release were negligible for the first 2 h in simulated gastric fluid (pH 1.2), and appreciable in simulated intestinal fluid (pH 6.8). The release data were fitted by various equations to define the release kinetic mechanism. In addition, the selected formulation (F16) was stable to the oxidation not only during the formulation process, but also after 3 months of storage at room temperature. In summary, these polynucleate alginate beads, produced by prilling technique, are promising systems for improving the intestinal specific delivery and bioavailability of health-promoting bioactive SR-oil.

The hydroxypropyl-ß-cyclodextrin-minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia.

The efficacy of minoxidil (MXD) ethanolic solutions (1%-5% w/v) in the treatment of androgenetic alopecia is limited by adverse reactions. The toxicological effects of repeated topical applications of escalating dose (0.035%-3.5% w/v) and of single and twice daily doses (3.5% w/v) of a novel hydroxypropyl-ß-cyclodextrin MXD GEL formulation (MXD/HP-ß-CD) and a MXD solution were investigated in male rats. The cardiovascular effects were evaluated by telemetric monitoring of ECG and arterial pressure in free-moving rats. Ultrasonographic evaluation of cardiac morphology and function, and histopathological and biochemical analysis of the tissues, were performed. A pharmacovigilance investigation was undertaken using the EudraVigilance database for the evaluation of the potential cancer-related effects of topical MXD. Following the application of repeated escalating doses of MXD solution, cardiac hypertrophy, hypotension, enhanced serum natriuretic peptides and K+ -ion levels, serum liver biomarkers, and histological lesions including renal cancer were observed. In addition, the administration of a twice daily dose of MXD solution, at SF rat vs human = 311, caused reductions in the systolic, diastolic, and mean blood pressure of the rats (-30.76 ± 3%, -28.84 ± 4%, and -30.66 ± 5%, respectively, vs the baseline; t test P < .05). These effects were not reversible following washout of the MXD solution. Retrospective investigation showed 32 cases of cancer associated with the use of topical MXD in humans. The rats treated with MXD HP-ß-CD were less severely affected. MXD causes proliferative adverse effects. The MXD HP-ß-CD inclusion complex reduces these adverse effects.

Corrigendum to "Immune Profile of Obese People and In Vitro Effects of Red Grape Polyphenols on Peripheral Blood Mononuclear Cells".

[This corrects the article DOI: 10.1155/2017/9210862.].

Administration of a polyphenol-enriched feed to farmed sea bass (Dicentrarchus labrax L.): Kidney melanomacrophages response.

The reinforcement of the defense mechanism of fish, through the administration of immunostimulants, is considered as a promising alternative to vaccines. Natural immunostimulants such as polyphenols, flavanoids, pigments and essential oils can modulate the innate immune response. In lower vertebrates, melano-macrophage centres, i.e. clusters of pigment-containing cells forming the extracutaneous pigment system, are wide-spread in the stroma of the haemopoietic tissue, mainly in kidney and spleen. In fishes, melano-macrophage centres play an important role in the immune response against antigenic stimulants and pathogens. In the present study, we evaluated the effect of a polyphenol-enriched diet on the health status of European sea bass (Dicentrarchus labrax L.). Farmed sea bass were administered a feed containing a phytocomplex, rich in catechins and epigallocatechins, which was obtained from the seeds of Canosina Nero di Troia Vitis vinifera and mixed with conventional feed at two different concentrations. The effects of such a diet were investigated in juvenile and commercial size samples, i.e. undergoing a short- and long-term period of diet, respectively, focusing on their extracutaneous pigmentary system and, in more detail, on the enzymatic activities leading to melanin biosynthesis. Our results show that prolonged dietary treatments with higher concentration of polyphenols might modulate tyrosinase activity and gene expression in commercial size fishes. An increase of melano-macrophage activity is correlated to a stimulation of cytoprotective functions against antigenic stimulants and pathogens, as an expression of a robust and protective adaptive immune response.

Immune Profile of Obese People and In Vitro Effects of Red Grape Polyphenols on Peripheral Blood Mononuclear Cells.

The in vitro ability of polyphenols, extracted from red grape, to modulate peripheral blood mononuclear cell responses has been evaluated in 20 obese (Ob) people. With regard to cytokine release in response to phorbol myristate acetate (PMA), levels of interleukin-2 (IL-2), interferon-γ (IFN-γ), IL-4, IL-10, and IL-17 were higher in the Ob than in healthy (H) subjects. Vice versa, IL-21 concentrations were detected only in H people but they were undetectable in the Ob counterpart. In general terms, levels of IL-1ß, IL-6, IL-8, and tumor necrosis factor-α were higher in Ob people when compared to H controls. On the other hand, polyphenols did not modify IFN-γ, IL-4, and IL-17 levels. However, an increase in IL-2 was observed in H individuals, whereas its levels were decreased in the Ob counterpart. Polyphenols significantly increased IL-10 release from H donors, whereas a trend to increase was observed in Ob people. In addition, polyphenols were able to significantly increase levels of H IL-21, while this was not the case in Ob people. Since IL-21 is an inducer of Th17 cells, it is likely that polyphenols may suppress the sources of this cytokine via production of IL-10. Accordingly, polyphenols decreased IL-1ß and IL-6 release in comparison to H controls.

Morphometrical and Morphological Alterations of Human Leukocytes Exposed to 1.8 GHz Electromagnetic Radiations: In Vitro Protective Effects Induced by Polyphenols.

BACKGROUND: Our recent findings have demonstrated that electromagnetic radiations (EMR) (1.8 GHz radiofrequency) are able to in vitro induce morphometrical and morphological modifications of human leukocytes from normal donors. METHODS: In view of the evidence that polyphenols exert many beneficial effects on plants, animals and humans, leukocytes from human peripheral blood were pre-treated for 1 h with two polyphenol preparations from red grape before EMR exposure (1.8 GHz). RESULTS: Our data will show that polyphenol pre-treatment reverts to normality the morphology of irradiated leukocytes in comparison to irradiated cells only. Conversely, leukocyte morphometry seems to be not affected by this treatment. CONCLUSION: Here, we demonstrate that polyphenols are also able to normalize leukocyte morphology per se altered before as well as after irradiation. Finally, a working hypothesis aimed at clarifying the protective mechanisms exerted by polyphenols on irradiated leukocytes will be illustrated.

Administration of a Polyphenol-Enriched Feed to Farmed Sea Bass (Dicentrarchus labrax L.) Modulates Intestinal and Spleen Immune Responses.

Farmed fish are exposed to a continuous antigenic pressure by microbial and environmental agents, which may lead to a condition of chronic inflammation. In view of the notion that polyphenols, largely contained in fruits and vegetables, are endowed with antioxidant and anti-inflammatory activities, farmed sea bass (Dicentrarchus labrax L.) have been administered with red grape polyphenol-enriched feed. Polyphenols were extracted from the seeds of Canosina Nero di Troia Vitis vinifera and mixed with conventional feed at two different concentrations (100 and 200 mg/kg, resp.). Fish samples collected at days 223 and 273, respectively, were evaluated for intestinal and spleen cytokine release as well as for spleen macrophage (MØ) and melanomacrophage center (MMC) areas and distribution. Data will show that in treated fish decrease of intestinal interleukin- (IL-) 1ß and IL-6 and increase of splenic interferon- (IFN-) γ occur. On the other hand, in the spleen reduction of MØ number seems to parallel increase in MMCs. Collectively, these data suggest that polyphenol-administered sea bass generate lower levels of intestinal proinflammatory cytokines, while producing larger amounts of spleen IFN-γ, as an expression of a robust and protective adaptive immune response. Increase of MMCs corroborates the evidence for a protective spleen response induced by feed enriched with polyphenols.

Human use of Leucoselect® Phytosome® with special reference to inflammatory-allergic pathologies in frail elderly patients.

Human ageing is characterized by several abnormalities of both innate and adaptive immune responses, thus leading to an increased frequency of infectious, inflammatory, allergic and autoimmune diseases. In elderly patients, among allergic diseases, asthma is a very common pathological event which complicates the dysfunction of many systems. Among a variety of natural products used to modulate the altered immune response, polyphenols have been shown to exert antiinflammatory activities in both young and aged persons. Here, special emphasis will be given to the the immune-modulating effects of Leucoselect® Phytosome® (a dietary supplement enriched in the flavonoid epigallocatechin) administered to frail elderly patients. Leucoselect® Phytosome® was able to upregulate the T helper (Th)1 response [increase in serum concentrations of interleukin (IL)-2 and interferon-γ]. On the other hand, IL-4 serum levels, as an index of Th2 function, fluctuated within normal ranges. Quite interestingly, in this cohort of frail aged patients from South Italy the balance between inflammation (IL-17) and anti-inflammation (IL-10) was preserved, thus suggesting that the Mediterranean diet might have been involved in the observed effects. In conclusion, these data support the ability of Leucoselect® Phytosome® to induce up-regulation of Th1 responses in frail elderly patients which may be beneficial in those patients affected by chronic allergic disorders.