Background/Objectives: Glucagon-like peptide-1 (GLP-1) is a nutritionally regulated incretin involved in the coordination of intestinal, hepatic, and adipose metabolic responses. Although plant-derived extracts are increasingly investigated for their metabolic effects, mechanistic evidence integrating multiple metabolic tissues remains limited. This study aimed to investigate the molecular effects of a combination of plant-derived extracts in an integrated in vitro gut-liver-adipose model. Methods: Differentiated Caco-2 monolayers were exposed to a standardised combination of plant-derived extracts obtained from Gastrodia elata, Morus alba, and Paeonia lactiflora. GLP-1 secretion and epithelial barrier integrity were assessed. Conditioned media from intestinal cells were applied to HepG2 hepatocytes, and downstream effects on lipid metabolism-related pathways were evaluated. Subsequently, conditioned media from hepatic cells were applied to differentiated 3T3-L1 adipocytes to assess lipid accumulation and metabolic signalling. Results: Exposure of intestinal cells to the extract combination significantly increased GLP-1 secretion without altering epithelial barrier integrity. Intestinal conditioned media were associated with reductions in intracellular triglyceride levels in hepatocytes and with modulation of markers linked to lipid handling, including resistin, FGF21, SREBP-1c, NRF2, Src, AMPK, SIRT1, and PGC1α, suggesting GLP-1-associated effects. In adipocytes, hepatic conditioned media decreased lipid accumulation and increased the levels of metabolic markers associated with adipocyte browning-related signalling, including UCP1, NOS, SIRT1, and STAT3. Conclusions: Within the limitations of this in vitro multi-organ model, these findings suggest that the tested combination of plant-derived extracts modulates cellular pathways related to GLP-1-associated metabolic signalling across intestinal, hepatic, and adipose systems. These results should be interpreted as mechanistic and hypothesis-generating, and further in vivo and clinical studies are required to confirm their physiological relevance.

Background: 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 endothelium, once considered merely a vascular lining responsible for selective permeability to water and electrolytes, is now recognised as a key regulator of vascular tone through the release of mediators such as oxylipins, nitric oxide, and hyperpolarizing factors. This in vitro study investigated the biological activity of Vesvein, a natural formulation containing Diosmin/Hesperidin, Ruscus aculeatus, Bromelain, and Ananas comosus, on intestinal and endothelial cells. Vesvein enhanced intestinal cell viability and preserved barrier integrity, as demonstrated by increased tight junction expression at both single and double concentrations. In endothelial cells, the compound improved parameters linked to venous insufficiency, elevating nitric oxide production by approximately 1.39-fold at a single dose and 1.65-fold at a double dose. These findings indicate a potential role for Vesvein in supporting endothelial health and vascular function in vitro. Preliminary evidence from intestinal models further suggests preserved barrier properties, which may positively influence absorption and bioavailability, thereby enhancing its vascular benefits.

Tremella fuciformis is high in polysaccharides, which have a structure made up of a straight chain of (1→3) α-D-mannan and side chains of glucuronic acid, xylose, and fucose. This study aimed to evaluate whether the non-animal hyaluronic acid extracted from Tremella fuciformis can maintain the chemical and physical characteristics of hyaluronic acid that ensure its biological functionality. Chemical and physical analyses such as hyaluronic content, screening of metals, purity, pH, nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (ATR/FTIR), and MALDI-TOF were performed. Chemical characterisation revealed that the most abundant polysaccharide in the extract was hyaluronic acid, accounting for ca. 87.76%, with a molecular weight above 2000 kDa. In addition, ATR/FTIR and NMR spectroscopy and MALDI-TOF analysis confirmed that Tremella fuciformis extract is a source of non-animal hyaluronic acid. In summary, every molecular attribute examined played a significant role in determining the functional qualities of the extract, indicating that a thoughtful choice of extraction technique can enhance its advantages.

Consciousness Expansion is a bioenergetic technique of the Summa Aurea® Method that acts on a physiological, mental, and, of course, energetic level to qualitatively improve the well-being of the person undergoing self-treatment. It can be seen as an energetic meditation whose main feature is the use of Scalar Energy, typical of the Method. This method can be seen as a complementary treatment, useful for managing the overall health of both healthy and sick people, with the aim of modulating and rebalancing the energy field of people through the use of the hands or at a distance. It reduces or eliminates pain and stress, improving mood and bringing harmony and well-being to the person. It also increases one\'s energy perception, balance, and proprioception. It also harmonizes and balances the heart rate, positively influencing the nervous system. The qualitative study is based on 100 participants in the Summa Aurea® Method courses, of whom over 50% are healthcare professionals. An 8-item questionnaire was used to survey the physiological changes in practitioners, specifically evaluating the analgesic effects. The items considered for this study were: 1 Headache 2 Muscle pain 3 Low back pain 4 Localized pain 5 Physical fatigue 6 Mental fatigue 7 Breathing difficulties 8 Stress The results obtained fully confirmed the research hypotheses.

Hyaluronic 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.

L’Espansione di Coscienza è una tecnica bioenergetica del Metodo Summa Aurea® che è in grado di agire a livello fisiologico, a livello mentale e ovviamente a livello energetico, per migliorare qualitativamente lo stato di benessere della persona in autotrattamento. Può essere vista come una meditazione energetica la cui peculiarità principale è l’utilizzo dell’Energia Scalare, tipica del Metodo. Tale metodica può essere vista come trattamento complementare, utile a gestire la globalità delle persone sane e malate, con l’obiettivo di modulare e riequilibrare il campo energetico delle persone attraverso l’uso delle mani o a distanza. Riduce o elimina, dolore e stress, migliorando l’umore e portando armonia e benessere nella persona. Aumenta inoltre le proprie capacità percettive dell’energia, il proprio equilibrio e la propriocezione. Armonizza e bilancia inoltre, il ritmo cardiaco, influenzando positivamente il Sistema Nervoso. Lo studio qualitativo è basato su 100 partecipanti ai corsi del Metodo Summa Aurea®, di cui oltre il 50% Operatori in ambito Medico sanitario. Attraverso un questionario con 8 item si è sondato i cambiamenti a livello fisiologico dei praticanti valutando in modo specifico gli effetti antalgici. Gli item presi in considerazione per questo studio riguardano: 1 Mal di Testa 2 Dolori muscolari 3 Lombalgia 4 Dolore localizzato 5 Stanchezza Fisica 6 Stanchezza Mentale 7 Difficoltà respiratorie 8 Stress I risultati ottenuti hanno pienamente confermato le ipotesi della ricerca.

During 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.

Neuropathy affects 7–10% of the general population and is caused by a lesion or disease of the somatosensory system. The limitations of current therapies highlight the necessity of a new innovative approach to treating neuropathic pain (NP) based on the close correlation between oxidative stress, inflammatory process, and antioxidant action. The advantageous outcomes of a novel combination composed of Hop extract, Propolis, Ginkgo Biloba, Vitamin B, and palmitoylethanolamide (PEA) used as a treatment was evaluated in this study. To assess the absorption and biodistribution of the combination, its bioavailability was first examined in a 3D intestinal barrier model that replicated intestinal absorption. Further, a 3D nerve tissue model was developed to study the biological impacts of the combination during the essential pathways involved in NP. Our findings show that the combination could cross the intestinal barrier and reach the peripheral nervous system, where it modulates the oxidative stress, inflammation levels, and myelination mechanism (increased NRG, MPZ, ERB, and p75 levels) under Schwann cells damaging. This study proves the effectiveness of Ginkgo Biloba, Propolis, Hop extract, Vitamin B, and PEA in avoiding nerve damage and suggests a potential alternative nutraceutical treatment for NP and neuropathies.

Vitamin D is increasingly recognized for its role in cardiovascular health beyond its well-established effects on bone metabolism. This review synthesizes findings from observational studies, interventional trials, and meta-analyses to clarify the mechanisms through which vitamin D impacts cardiovascular health, including its influence on vascular function, inflammation, and metabolic pathways. Additionally, this review emphasizes the importance of a personalized approach to vitamin D supplementation, integrating individual cardiovascular risk profiles, baseline vitamin D levels, and comorbid conditions, such as hypertension and diabetes. While current evidence supports the association between low vitamin D levels and increased cardiovascular mortality, this work contributes novel insights by proposing tailored strategies for supplementation, particularly for high-risk subgroups. Practical recommendations for implementing these strategies in clinical practice are also discussed, providing a framework for optimizing cardiovascular outcomes through individualized vitamin D management.

Background: Peripheral neuropathy is caused by a malfunction in the axons and myelin sheaths of peripheral nerves and motor and sensory neurons. In this context, nonpharmacological treatments with antioxidant potential have attracted much attention due to the issues that some conventional pharmaceutical therapy can generate. Most of these treatments contain lipoic acid, but issues have emerged regarding its use. Considering this, the present study evaluated the beneficial effects of nutraceuticals based on Gastrodiae elata dry extract 10:1 or lipoic acid in combination with other substances (such as citicholine, B vitamins, and acetyl L-carnitine). Method: To assess the combination’s absorption and biodistribution and exclude cytotoxicity, its bioavailability was first examined in a 3D intestinal barrier model that replicated oral ingestion. Subsequently, a 3D model of nerve tissue was constructed to investigate the impacts of the new combination on the significant pathways dysregulated in peripheral neuropathy. Results: Our findings show that the novel combination outperformed in initial pain relief response and in recovering the mechanism of nerve healing following Schwann cell injury by successfully crossing the gut barrier and reaching the target site. Conclusion: This article describes a potential alternative nutraceutical approach supporting the effectiveness of combinations with Gastrodiae elata extract in decreasing neuropathy and regulating pain pathways.

Various hindbrain nuclei have been demonstrated to be involved in the control of the cardiovascular reflexes elicited by both non-noxious and noxious gastric distension, through parasympathetic and sympathetic activation. The different role played by the branches of autonomic nervous system in exerting these effects and their crosstalk in relation to low-/high-pressure distension rate has not been examined yet. Therefore, in the present work, monolateral and bilateral vagotomy and splanchnicotomy were performed in anesthetised rats to analyse the involvement of hindbrain nuclei in haemodynamic changes caused by gastric distension at high (80 mmHg) and low (15 mmHg) pressure. The analysis of c-Fos expression in neuronal areas involved in cardiovascular control allowed us to examine their recruitment in response to various patterns of gastric distension and the crosstalk between vagal and splanchnic systems. The results obtained show that the low-pressure (non-noxious) gastric distension increases both heart rate and arterial blood pressure. In addition, the vagus nerve and hindbrain nuclei, such as nucleus ambiguous, ventrolateral medulla and lateral reticular nucleus, appear to be primarily involved in observed responses. In particular, we have found that although vagus nerve plays a central role in exerting those cardiovascular reflex changes at low gastric distension, for its functional expression an intact splanchnic system is mandatory. Hence, the absence of splanchnic input attenuates pressor responses or turns them into depressor responses. Instead at high-pressure (noxious) gastric distension, the splanchnic nerve represents the primary component in regulating the reflex cardiovascular effects.

Palmitoylethanolamide (PEA) is a highly lipophilic molecule with low solubility, making absorption difficult. Recent techniques like micronisation, ultra-micronisation and combining PEA with solvents have improved their bioavailability and stability. Our study analysed particle size differences and absorption kinetics using specific solvents (PEAΩ and PEA DynoΩ) over time (0.5 h–6 h) in a dose-dependent manner (200 mg–1800 mg). The results showed that PEAΩ and PEA DynoΩ achieved 82–63% absorption at 3 h, compared to 30–60% for micronised, ultra-micronised PEA and a commercial product, highlighting the optimal dose range of 300 mg–600 mg. In addition, a 3D model of the peripheral nerve was utilised to explain the efficacy after gut passage and support the most effective dose (300 mg or 600 mg) achieved at the gut level. PEAΩ and PEA DynoΩ, which are associated with better intestinal bioavailability compared to PEA-micronised, PEA ultra-micronised and a commercial product, have allowed not only a reduction in the inflammatory context but also an improvement of peripheral nerve well-being by increasing specific markers like MPZ (26–36% vs. 8–15%), p75 (25–32% vs. 13–16%) and NRG1 (22–29.5% vs. 11–14%). These results highlight the potential of advanced PEA formulations to overcome solubility challenges and maintain in vitro efficacy, modulating peripheral nerve well-being.

The gut–brain axis is a bidirectional relationship between the microbiota and the brain; genes related to the brain and gut synaptic formation are similar. Research on the causal effects of gut microbiota on human behavior, brain development, and function, as well as the underlying molecular processes, has emerged in recent decades. Probiotics have been shown in several trials to help reduce anxiety and depressive symptoms. Because of this, probiotic combinations have been tested in in vitro models to see whether they might modulate the gut and alleviate depression and anxiety. Therefore, we sought to determine whether a novel formulation might affect the pathways controlling anxiety and depression states and alter gut barrier activities in a 3D model without having harmful side effects. Our findings indicate that B. bifidum novaBBF7 10 mg/mL, B. longum novaBLG2 5 mg/mL, and L. paracasei TJB8 10 mg/mL may influence the intestinal barrier and enhance the synthesis of short-chain fatty acids. Additionally, the probiotics studied did not cause neuronal damage and, in combination, exert a protective effect against the condition of anxiety and depression triggered by L-Glutamate. All these findings show that probiotics can affect gut function to alter the pathways underlying anxiety and depression.

Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin (βNS-CDI 1:4) nanosponges (NS) (defined as VitD3NS). Therefore, its activity has been evaluated on two different gut–brain axes (healthy gut/degenerative brain and inflammatory bowel syndrome gut/degenerative brain axis). At the gut level, VitD3-NS mitigated liposaccharide-induced damage (100 ng/mL; for 48 h), restoring viability, integrity, and activity of tight junctions and reducing ROS production, lipid peroxidation, and cytokines levels. Following intestinal transit, VitD3-NS improved the neurodegenerative condition in the healthy axis and the IBS model, suggesting the ability of VitD3-NS to preserve efficacy and beneficial effects even in IBS conditions. In conclusion, this study demonstrates the ability of this novel form of VitD3, named VitD3-NS, to act on the gut–brain axis in healthy and damaged conditions, emphasizing enhanced biological activity through VitD3 complexation, as such complexation increases the beneficial effect of vitamin D3 in both the gut and brain by about 50%.

This review aims to argue how using probiotics can improve anxiety and depressive behaviour without adverse effects, also exploring the impact of postbiotics on it. Specifically, probiotics have drawn more attention as effective alternative treatments, considering the rising cost of antidepressant and anti-anxiety drugs and the high risk of side effects. Depression and anxiety disorders are among the most common mental illnesses in the world's population, characterised by low mood, poor general interest, and cognitive or motor dysfunction. Thus, this study analyzed published literature on anxiety, depression, and probiotic supplementation from PubMed and Scopus, focusing on the last twenty years. This study focused on the effect of probiotics on mental health as they have drawn more attention because of their extensive clinical applications and positive impact on various diseases. Numerous studies have demonstrated how the gut microbiota might be critical for mood regulation and how probiotics can affect host health by regulating the gut-brain axis. By comparing the different works analysed, it was possible to identify a strategy by which they are selected and employed and, at the same time, to assess how the effect of probiotics can be optimised using postbiotics, an innovation to improve mental well-being in humans.

Chronic oxidative stress has been consistently linked to age-related diseases, conditions, and degenerative syndromes. Specifically, the brain is the organ that significantly contributes to declining quality of life in ageing. Since the body cannot completely counteract the detrimental effects of oxidative stress, nutraceuticals' antioxidant properties have received significant attention in recent years. This study assesses the potential health benefits of a novel combination of glutathione, vitamin D3, and N-acetylcysteine. To examine the combination's absorption and biodistribution and confirm that it has no harmful effects, the bioavailability of the mixture was first evaluated in a 3D model that mimicked the intestinal barrier. Further analyses on the blood-brain barrier was conducted to determine the antioxidant effects of the combination in the nervous system. The results show that the combination reaches the target and successfully crosses the blood-brain and intestinal barriers, demonstrating enhanced advantages on the neurological system, such as a reduction (about 10.5%) in inflammation and enhancement in cell myelination (about 20.4%) and brain tropism (about 18.1%) compared to the control. The results support the cooperative effect of N-acetylcysteine, vitamin D3, and glutathione to achieve multiple health benefits, outlining the possibility of an alternative nutraceutical approach.