1,720,972 research outputs found
Neuroprotective Pathway Modulation by a Novel Coriandrum sativum, N-Acetylcysteine and Glutathione-Based Formulation: Insights from In Vitro 3D Models
Full text linkPain remains a major clinical challenge due to its complex physiopathology and limited treatment options. In this context, several supplements based on palmitoylethanolamide (PEA) and alpha-lipoic acid (ALA) are known for their neuroprotective properties. ALA-based supplements have shown potential, but concerns about adverse effects persist. This study examines the formulations of two commercial products based on ALA and PEA, IperALA® and IperALA® Forte, in which ALA and vitamin D3 are replaced with Coriandrum sativum extract (C. sativum e.s.), N-acetylcysteine (NAC) and glutathione (GSH), assessing improvement of neuroprotective, anti-inflammatory and analgesic properties of the new formulation. Intestinal, blood–brain barrier (BBB), and central nervous system (CNS) models were sequentially stimulated with the test compounds. Both formulations were assessed for cytotoxicity, barrier integrity, permeability, oxidative stress, inflammation, and neuroprotection-related biomarkers. IperALA® Forte demonstrated superior performance compared to IperALA® and individual agents. It enhanced cell viability, preserved intestinal and BBB integrity, and improved compound permeability. Notably, it reduced ROS and pro-inflammatory cytokines (TNFα, IL-1), while increasing analgesic markers (CB2R, GABA) in the central system. The replacement of ALA and vitamin D3 with C. sativum, NAC, and GSH in IperALA® Forte significantly improved the neuroprotective, antioxidant, and anti-inflammatory profile of the supplement. These results indicate a possible connection between the observed neuroprotective properties and the pathways involved in nociception and pain regulation, stating the hypothetical potential relevance of this approach for the treatment of pain-related conditions
Neuroinflammation-Modulating Properties Combining Glutathione, N-Acetylcysteine, and Uridine Monophosphate in a Formulation Supplement: An In Vitro Study
Full text linkBackground: Neuropathic pain is a complex condition often resistant to current therapies due to limited efficacy and adverse effects. Nutraceuticals offer promising alternatives, combining antioxidant and anti-inflammatory properties with good tolerability. This study aimed to compare the effects of a commercial nutraceutical formulation, SUPERALA CARNITINE® (Pharma Suisse Laboratories SpA, Milan, Italy), containing Alpha-Lipoic Acid (ALA), with a novel formulation, called SUPERALA CARNITINE® Forte, where ALA and vitamin B6 were replaced by N-acetylcysteine (NAC), Glutathione (GSH), and Uridine monophosphate (UMP). Methods: An indirect gut–peripheral nerve axis was employed to simulate oral absorption, metabolism, and effect on nervous tissues using 3D in vitro models. Both formulations and their individual components were assessed for cytotoxicity and permeability in the gut model (Caco-2 cells in Transwell®) and, after gut metabolism, for antioxidant capacity, anti-inflammatory activity, and neuroprotective potential in the peripheral nerve model. Results: SUPERALA CARNITINE® Forte improved cell viability and favoured the maintenance of intestinal integrity, showing enhanced permeability, and significantly reduced oxidative stress (OS) and pro-inflammatory cytokines (TNF-α, IL-2) at the peripheral nervous system. In addition, it increased levels of neuronal markers (p75, MPZ, NRG1, ERβ) and decreased NaV1.7 and NaV1.8 activity, indicating greater neuroprotection and analgesic modulation than the ALA-based formula.
Conclusions: The replacement of ALA and vitamin B6 with NAC, GSH, and UMP produced favorable responses in vitro on neuronal cells, supporting a hypothetical potential interest in this nutraceutical combination and justifying further future in vivo investigations
Analysis of the Beneficial Effects of Probiotics on the Gut–Prostate Axis Using Prostatic Co-Culture Model
Full text linkThe link between the gut environment and the prostate has recently been proposed as a potential therapeutic approach for treating benign prostatic hyperplasia (BPH). Therefore, this study examined the advantages of a novel oral probiotic supplement to improve intestinal health and treat BPH. A 3D intestinal barrier model that simulated oral intake was used to analyse the combined regulative abilities of Bifidobacterium longum and Bifidobacterium psychaerophilum. Then, a co-culture prostatic model was used to investigate the biological consequences of the combination under conditions mimicking BPH. The results show the connection between the gut microbiome and prostate disease since the probiotics successfully modulate the primary mechanism involved in the pathogenesis of BPH. Indeed, after the intestinal passage, the mediators released from B. longum and B. psychaerophilum induced a substantial decrease in reactive oxidative species of about 6 times and inflammation (about 5 times regarding interleukine-6 and 10) and a sharp increase in testosterone and serotonin levels (about 95%). Further, proliferation and BPH principal mediators (such as androgen and dihydrotestosterone) were highly affected and nearly restored to physiological levels. Thus, BPH can be directly affected by probiotic supplementation; specifically, B. longum and B. psychaerophilum, in combination, seem able to promote the mitigation of this disease
Improved Iron Uptake and Metabolism Through Combined Heme and Non-Heme Iron Supplementation: An In Vitro Study
Full text linkIron is essential for numerous physiological processes, including oxygen transport, energy
metabolism, and immune function. This study evaluated the efficacy and safety of three iron
formulations combining heme and non-heme iron, comparing them with existing market
products and the original form of iron. The formulations tested were GlobiFer® Forte, a
combination of heme and non-heme iron containing 18 mg of elemental iron (hereinafter
referred to as nutraceutical product 1); GlobiFer®, a combination of heme and non-heme
iron containing 14 mg of elemental iron (hereinafter referred to as nutraceutical product
2); and a double dose of nutraceutical product 2. Using an in vitro 3D intestinal barrier
model, all three formulations significantly increased tight junction protein expression and
TEER values, indicating preserved barrier integrity. Iron absorption analysis revealed
that all three iron formulations had higher absorption rates than controls. Nutraceutical
product 1 showed the highest absorption, associated with increased expression of the iron
transporters such as the primary non-heme iron transporter, DMT1, and the leading apical
heme transporter, HCP-1. All three new formulations increased ferritin and ferroportin
levels, markers of systemic iron storage and regulation. Nutraceutical product 1 was found
to be the most effective, based on percentage. Overall, combining heme and non-heme
iron improved intestinal absorption and supported iron metabolism, with Nutraceutical
Product 1 proving the most promising in terms of efficacy and safety. These results support
the development of optimised dual-source iron supplements to improve bioavailability
and maintain intestinal barrier integrity, prerequisites for better efficacy and tolerability in
clinical use
Non-Animal Hyaluronic Acid and Probiotics Enhance Skin Health via the Gut–Skin Axis: An In Vitro Study on Bioavailability and Cellular Impact
Full text linkHyaluronic acid (HA) represents a pivotal component of the extracellular matrix,
particularly within the context of the skin. The absorption and metabolism of orally ingested
HA have been extensively investigated due to the prevalence of HA-based supplements.
The objective of this study was to evaluate the impact of a combination of non-animal
HA and Bifidobacterium longum novaBLG1 on dermal health following intestinal transit.
The bioavailability of the compound was evaluated using a model that reproduced the
human intestinal barrier in vitro, and its biological effects were investigated on skin cells
via the gut–skin axis. The results demonstrated that probiotics augmented the absorption
of non-animal HA by approximately 30% in comparison to non-animal HA alone and by
82% in comparison to sodium hyaluronate. Furthermore, the combination demonstrated a
notable enhancement in skin cell proliferation, with increases of 16%, 8%, and 29.7% over
144 h in comparison to non-animal hyaluronan, Bifidobacterium longum novaBLG1, and
sodium hyaluronate, respectively. The combination was observed to positively affect all
markers of skin health and well-being, achieving its goals without any adverse effects on
the gut. This approach offers a novel method for enhancing skin health
In Vitro Neuroprotective Effects of a Mixed Extract of Bilberry, Centella asiatica, Hericium erinaceus, and Palmitoylethanolamide
Full text linkOxidative stress, driven by impaired antioxidant defence systems, is a major contributor to cognitive decline and neurodegenerative processes in brain ageing. This study investigates the neuroprotective effects of a natural compound mixture—composed of Hericium erinaceus, Palmitoylethanolamide, Bilberry extract, and Centella asiatica—using a multi-step in vitro strategy. An initial evaluation in a 3D intestinal epithelial model demonstrated that the formulation preserves barrier integrity and may be bioaccessible, as evidenced by transepithelial electrical resistance (TEER) and the expression of tight junctions. Subsequent analysis in an integrated gut–brain axis model under oxidative stress conditions revealed that the formulation significantly reduces inflammatory markers (NF-κB, TNF-α, IL-1β, and IL-6; about 1.5-fold vs. H2O2), reactive oxygen species (about 2-fold vs. H2O2), and nitric oxide levels (about 1.2-fold vs. H2O2). Additionally, it enhances mitochondrial activity while also improving antioxidant responses. In a co-culture of neuronal and astrocytic cells, the combination upregulates neurotrophic factors such as BDNF and NGF (about 2.3-fold and 1.9-fold vs. H2O2). Crucially, the formulation also modulates key biomarkers associated with cognitive decline, reducing APP and phosphorylated tau levels (about 98% and 1.6-fold vs. H2O2) while increasing Sirtuin 1 and Nrf2 expression (about 3.6-fold and 3-fold vs. H2O2). These findings suggest that this nutraceutical combination may support the cellular pathways involved in neuronal resilience and healthy brain ageing, offering potential as a functional food ingredient or dietary supplement
Analysis of the Combined Effects of a Novel Combination of Hypersmin, Pumpkin Seed and Amaranthus Extracts in an In Vitro Model of Chronic Venous Insufficiency
Full text linkBackground: Venous hypertension is the primary cause of the disorder known as chronic venous insufficiency (CVI), which affects the lower extremities’ venous system. Because of its biological proper ties, which include anti-inflammatory, antioxidant, and vascular tone enhancement, medicinal herbs and natural substances are highly recommended for treating CVI. Therefore, this study examined the advantages of a novel combination composed of hypersmin, pumpkin seed and amaranthus extracts (named MIX) in modulating different parameters involved with CVI. Methods: The capacity of these natural compounds to pass across the intestinal barrier and reach the bloodstream was examined using a 3D intestinal barrier model that mimics oral ingestion. The biological effects of the MIX were then compared to those of a commercial product using an in vitro CVI model. Results: The findings demonstrate that the new MIX significantly reduced inflammation while increasing nitric oxide production. The MIX was more successful than the commercial product in reducing apoptosis while restoring vasal tone and extracellular matrix activity. Conclusions: This work has therefore demonstrated the positive benefits of extracts from amaranthus, pumpkin seed and hypersmin in the context of CVI, raising the prospect of creating a unique combination for patients with CVI
The Combined Effect of Green Tea, Saffron, Resveratrol, and Citicoline against Neurodegeneration Induced by Oxidative Stress in an In Vitro Model of Cognitive Decline
Full text linkDuring ageing, the brain is vulnerable to a growing imbalance of the antioxidant defence system, resulting in increased oxidative stress. This condition may be mainly responsible for cognitive decline, resulting in synaptic transmission disruptions and the onset of neuronal dysfunction. In this context, developing efficient preventive and therapeutic strategies against increased oxidative stress and decreased antioxidant defence mechanisms should be considered a public health priority to promote healthy ageing. Therefore, the current study explored the benefits of a novel combination of green tea, saffron, trans-Reveratrol, and citicoline, called MIX, on improving intracellular processes to ameliorate the mechanisms linked to cognitive decline under oxidative stress conditions. First, the ability of MIX to cross the blood-brain barrier (BBB) was evaluated in an in vitro model, analysing TEER value and the specific tight junctions; second, the CCF-STTG1 cell line was pretreated with 200 μM H2O2 for 30 min to explore the effects of the single active compounds and their combination under oxidative stress conditions. Our results demonstrated for the first time the synergistic effects of the new combination to improve the absorption rate of individual agents through the BBB and maintain its integrity. Subsequently, further research was done to assess the positive role of the combination to counteract oxidative damage; as expected, MIX restored the neurodegenerative state activated by 200 μM H2O2, reducing mitochondrial damage, and improving survival pathways. Additionally, MIX acted as a regulator of both cellular energy metabolism and apoptosis, reducing the inflammatory state activated by oxidative stress. Finally, MIX can balance neurotrophin production to prevent mitochondrial disruption. In conclusion, MIX counteracted the adverse effects of brain oxidative stress, suggesting that this new proposed formulation prevents the molecular mechanisms underlying the onset of cognitive decline, even in support of conventional therapy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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