Evaluation of the Immunomodulatory Effects of a Probiotics and Natural Extract-Based Formulation in Bacterial-Induced Prostatitis.

Among the many factors inducing prostate inflammation, bacterial contribution is potentially underrated according to the scientific community. Bacterial prostatitis is characterized by modifications of the prostatic microenvironment, mainly driven by the immune system. Macrophages play a major role in bacterial prostatitis, secreting a plethora of proinflammatory and chemoattractive cytokines and proteolytic enzymes able to degrade the ECM, so facilitating the invasion of other immune cells. Consequently, macrophages represent a link between bacterial infection and prostate inflammation, as well as being the main target of prostate anti-inflammatory drugs and dietary supplements. This study aims to investigate the effect of a formulation composed of active principles and a probiotic strain with a particular focus on the anti-inflammatory effect in an in vitro bacterial prostatitis model. The results obtained showed that the formulation reduces the inflammatory response of prostatic epithelium induced by bacterial infection. This effect is mediated by the modulation of activated macrophages. Analysis of the cytokines released highlights that the tested formulation is able to reduce the expression of key proinflammatory cytokines involved in the pathogenesis of prostate diseases, in particular prostate cancer, and represents a valuable tool to prevent bacterial prostatitis and ensure favorable prostate health.

Prostatic Therapeutic Efficacy of LENILUTS®, a Novel Formulation with Multi-Active Principles.

Lower Urinary Tract Symptoms (LUTs) in men are usually associated to benign prostatic hyperplasia (BPH), a non-malignant prostate enlargement. Unfortunately, BPH etiology is still unclear. Recent works highlighted a relevant inflammation role in BPH onset and development. Consequently, to complement the 5-α reductase (and α-adrenergic receptor agonists-based therapy, an anti-inflammatory therapy should be devised. To reduce potential adverse effects of multi-drug treatment, plant extract-based therapies are becoming increasingly common. Serenoa repens, the main phytotherapic treatment for BPH, is not sufficient to front the multi-faceted etiology of BPH. In response to this, a novel, multiple phytotherapic agents-based formulation, LENILUTS®, was developed. In the present work, we compared, using an in vitro approach, the prostatic safety and efficacy of LENILUTS® with a commercial formulation, based only on Serenoa repens, and a 5αR inhibitor, Dutasteride. Furthermore, preliminary in vitro experiments to investigate the active principles, bioaccessibility and bioavailability of LENILUTS® were performed. Our results showed a better prostatic safety and therapeutic efficacy of LENILUTS® compared to the commercial formulation and Dutasteride, with increased anti-inflammatory, and pro-apoptotic activity, and a stronger inhibitory effect on the release of the key enzyme 5αR and Prostatic-Specific Antigen (PSA). The limited bioaccessibility and bioavailability of the active principles of LENILUTS® were highlighted. Considering the results obtained, the LENILUTS® formulation is more promising for BPH and LUTs therapy compared to formulations based on Serenoa repens only, but further efforts should be made to improve the bioaccessibility and bioavailability of the active principles.

Intestinal Absorption Study of a Granular Form of Ferric Pyrophosphate.

Iron deficiency is one of the most prevalent nutritional disorders worldwide. The standard treatment involves iron supplementation, but this task is challenging because of poor solubility and organoleptic issues. Moreover, the need to increase iron bioavailability represents a challenge for treating iron-related disorders. In this study, gastroresistance and iron intestinal absorption of an innovative granular formulation composed of ferric pyrophosphate, modified starch and phospholipids branded as Ferro Fosfosoma® was investigated. Gastroresistant properties were studied using standard protocols, and a bioaccessible fraction was obtained by exposing a food supplement to in vitro digestion. This fraction was used for investigating iron absorption in Caco-2 and human follicle-associated intestinal epithelium (FAE) models. Ferro Fosfosoma® showed an improved resistance to gastric digestion and higher intestinal absorption than ferric pyrophosphate salt used as a control in both models. In the FAE model, Ferro Fosfosoma® induces larger iron absorption than in the Caco-2 monolayer, most likely due to the transcytosis ability of M cells. The larger iron absorption in the Ferro Fosfosoma®-treated FAE model corresponds to higher ferritin level, proving physiological iron handling that was once delivered by granular formulation. Finally, the formulation did not induce any alterations in viability and barrier integrity. To conclude, Ferro Fosfosoma® favors iron absorption and ferritin expression, while preserving any adverse effects.

Anticholesterolemic Activity of Three Vegetal Extracts (Artichoke, Caigua, and Fenugreek) and Their Unique Blend.

Hepatic-related diseases, in particular hyperlipidemia and hypercholesterolemia, are a thorn on the side of the national health institutes around the globe. Indeed, liver lipid and cholesterol dysregulation could lead to atherosclerotic plaque formation and cardiovascular diseases. Currently, statin administration and monacolin K consumption are the main therapies proposed to counter this alarming connection, but relevant side effects are known. To overcome this issue, safe nutraceutical formulations and/or vegetal extracts, endowed with anticholesterolemic activity, could be instrumental in hypercholesterolemia prevention and treatment. In the present work, the anticholesterolemic efficacy of three vegetal extracts used in traditional medicine (artichoke, caigua, and fenugreek), their unique blend (ACFB), and the monacolin K-containing red yeast extract (RYR), was investigated with an in vitro approach based on hepatic cell line HepG2. The impact on cholesterol of the three extracts, their blend, and RYR were investigated by determining hepatocyte total and free cholesterol and bile acids biosynthesis. According to our results, the anticholesterolemic activity of the vegetal extracts was confirmed, and a novel choleretic activity of caigua extract was evidenced. ACFB showed to be safer than RYR while showing a similar effect on total and free cholesterol and bile acids synthesis compared to it. The anticholesterolemic activity of the blend was obtained with lower vegetal extract concentrations compared with the single vegetal extract, potentially indicating an additive effect between the extracts. In conclusion, the vegetal extracts and their blend, ACFB, are safe and are endowed with anticholesterolemic activity, potentially providing complementary therapies to the statin-based ones for hyperlipidemia and hypercholesterolemia-related complications.

Comparative Evaluation of Intestinal Absorption and Functional Value of Iron Dietary Supplements and Drug with Different Delivery Systems.

Iron is a fundament micronutrient, whose homeostasis is strictly regulated. Iron deficiency anemia is among the most widespread nutritional deficiencies and its therapy, based on dietary supplement and drugs, may lead to severe side effects. With the aim of improving iron bioavailability while reducing iron oral therapy side effects, novel dietary supplements based on innovative technologies-microencapsulation, liposomes, sucrosomes-have been produced and marketed. In the present work, six iron dietary supplements for different therapeutic targets were compared in terms of bioaccessibility, bioavailability, and safety by using an integrated in vitro approach. For general-purpose iron supplements, ME + VitC (microencapsulated) showed a fast, burst intestinal iron absorption kinetic, which maintained iron bioavailability and ferritin expression constant over time. SS + VitC (sucrosomes), on the other side, showed a slower, time-dependent iron absorption and ferritin expression trend. ME + Folate (microencapsulated) showed a behavior similar to that of ME + VitC, albeit with a lower bioavailability. Among pediatric iron supplements, a time-dependent bioavailability increase was observed for LS (liposome), while PIC (polydextrose-iron complex) bioavailability is severely limited by its poor bioaccessibility. Finally, except for SS + VitC, no adverse effects on intestinal mucosa vitality and barrier integrity were observed. Considering obtained results and the different therapeutic targets, microencapsulation-based formulations are endowed with better performance compared to the other formulations. Furthermore, performances of microencapsulated products were obtained with a lower iron daily dose, limiting the potential onset of side effects.

In vitro evaluation of different organic matrices used to modulate silicon bioavailability.

Silicon (Si) has numerous health properties. It is an element of the extracellular matrix; it is involved in collagen synthesis, bone mineralization, and immune system modulation; and it reduces metal accumulation in Alzheimer's disease and the risk of atherosclerosis. Given its poor intestinal absorption, Si is ingested in the form of orthosilicic acid (OSA) to promote its bioavailability. The aim of this work was to compare different commercial dietary supplements containing stabilized OSA to ascertain their bioaccessibility, bioavailability, and safety in a model of human intestinal epithelium. Biocompatibility with the glycocalyx was also investigated. Supplements containing collagen, maltodextrins, and choline as OSA stabilizers were analyzed. Bioaccessibility was explored by means of an in vitro digestive process. Bioavailability was investigated using a Caco2 cell line alone, or co-culturing with a HT29-MTX cell line. The safety of the compounds tested (in terms of intestinal epithelium integrity) was judged on the grounds of MTS assay, transepithelial electrical resistance, and apparent permeability. The three formulations were also tested in a Caco2 cell model of intestinal glycocalyx Si retention. The choline-formulated OSA formulation outperformed the maltodextrin-stabilized supplement, with a Si bioavailability about 14 times higher (P < .05). The choline-formulated OSA formulation increased cell permeability, with consequent intestinal epithelium disruption. The supplements' absorption and bioavailability (and harmfulness) differed considerably, depending on the OSA stabilizer involved. Of the three formulations tested, the collagen-formulated OSA represents the best Si dietary supplement.

Lipomatrix: A Novel Ascorbyl Palmitate-Based Lipid Matrix to Enhancing Enteric Absorption of Serenoa Repens Oil.

The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in water. The major reason for the poor bioavailability of lipophilic natural compounds after oral uptake in humans is related to their reduced solubility in enteric water-based fluids, leading to an ineffective contact with absorbing epithelium. The main goal to ensure efficacy of such compounds is then creating technological conditions to deliver them into the first enteric tract as hydro-dispersible forms to maximize epithelial absorption. The present work describes and characterizes a new technological matrix (Lipomatrix, Labomar Research, Istrana, TV, Italy) based on a molten fats core in which Ascorbyl Palmitate is embedded, able to deliver lipophilic compounds in a well-dispersed and emulsified form once exposed to duodenal fluids. Authors describe and quantify Lipomatrix delivery of Serenoa repens oil through an innovative in vitro model of human gastro-enteric digestion, reporting results of its improved bioaccessibility, enteric absorption and efficacy compared with not formulated Serenoa repens oil-containing commercial products using in vitro models of human intestine and prostatic tissue.

Insights into the oligomerization process of the C-terminal domain of human plasma membrane Ca²+-ATPase.

Plasma membrane calcium pumps (PMCAs) sustain a primary transport system for the specific removal of cytosolic calcium ions from eukaryotic cells. PMCAs are characterized by the presence of a C-terminal domain referred to as a regulatory domain. This domain is target of several regulatory mechanisms: activation by Ca²+-calmodulin complex and acidic phospholipids, phosphorylation by kinase A and C, proteolysis by calpain and oligomerization. As far as oligomerization is concerned, the C-terminal domain seems to be crucial for this process. We have cloned the C-terminal domain of the human PMCA isoform 1b, and characterized its properties in solution. The expressed protein maintains its tendency to oligomerize in aqueous solutions, but it is dissociated by amphipathic molecules such as diacylglycerol and sodium dodecyl sulphate. The presence of sodium dodecyl sulphate stabilizes the domain as a compact structure in monomeric form retaining the secondary structure elements, as shown by small angle neutron scattering and circular dichroism measurements. The importance of oligomerization for the regulation of PMCA activity and intracellular calcium concentration is discussed.