Search Results (21)

Cardiovascular–Kidney–Metabolic (CKM) syndrome arises from interrelated cardiovascular, renal, and metabolic pathways that require coordinated therapeutic strategies. This narrative review synthesizes recent systematic reviews, meta-analyses, and original studies to evaluate the translational application of lifestyle medicine (LM) for CKM management. Evidence indicates that LM interventions targeting the six pillars of practice (nutrition, physical activity, stress management, sleep, social support, and avoidance of risky substances) can improve blood pressure, lipid profiles, glycemic control, and weight, with benefits that complement or at times rival pharmacotherapy. We outline opportunities at the LM–drug interface, including sodium-glucose cotransporter-2 inhibitors and nutrient-stimulated hormone agents such as GLP-1 and GIP, and highlight the need to test synergy and sequencing with LM. Persistent implementation barriers include prioritization of drug-centric care and limited protocolized delivery; the AHA 5A model and digital health tools, including wearables that enable real-time feedback, provide practical routes for integration. Marginalized populations carry a disproportionate burden of CKM, underscoring the need for equitable, culturally tailored approaches. Sex-specific gaps, particularly in post-menopausal lipid metabolism and insulin sensitivity, point to the promise of genomic and nutraceutical personalization. Future work should use preregistered, adequately powered multimodal trials to establish durable, scalable pathways for CKM care. Full article

Adult neurogenesis is well established in canonical niches—the dentate gyrus and the subventricular zone, where aerobic exercise reliably enhances progenitor proliferation, survival, and synaptic integration via increased cerebral blood flow, neurotrophins (e.g., BDNF, IGF-1), neurotransmitter regulation, and reduced neuroinflammation. Nutraceuticals (e.g., polyphenols, omega-3, creatine, vitamins) further support neuroplasticity and neuronal survival through convergent trophic, anti-inflammatory, and metabolic pathways. By contrast, the hypothalamus, a metabolically pivotal, non-canonical niche, remains comparatively understudied. Here, we synthesize anatomical and functional features of hypothalamic neural stem cells, primarily tanycytes (α1, α2, β1, β2), which line the third ventricle and differentially contribute to neuronal activity regulation, metabolic signaling, and cerebrospinal fluid–portal vasculature coupling, thereby linking neurogenesis to endocrine control. Notably, tanycytes can form neurospheres in vitro, enabling mechanistic interrogation. Although evidence for adult hypothalamic neurogenesis in humans is debated due to methodological constraints, animal data suggest potential relevance to disorders characterized by neuronal loss, metabolic dysregulation, and impaired neuroendocrine function. We propose that an integrative framework is timely: exercise and diet likely interact in the hypothalamic niche through shared mediators (BDNF, IGF-1, CNTF, GPR40) and exercise-derived signals (e.g., lactate, IL-6) that may be complemented by defined nutraceuticals. Yet critical uncertainties persist, including the extent of bona fide hypothalamic neurogenesis, nucleus-specific responses (arcuate nucleus, paraventricular nucleus, ventromedial hypothalamic nucleus), and the mechanistic integration of lifestyle signals in this region. To address these gaps, we outline actionable priorities: (i) single-cell and lineage-tracing studies of tanycyte subtypes under distinct training modalities (aerobic, high-intensity interval training, resistance); (ii) combinatorial interventions pairing structured exercise with nutraceuticals to test synergy on progenitor dynamics and inflammation; and (iii) multi-omics and translational studies to identify biomarkers and establish clinical relevance. Clarifying these interactions will determine whether lifestyle and supplementation strategies can synergistically modulate hypothalamic neurogenesis and inform therapies for neurological, neuropsychiatric, and metabolic disorders. Full article

The encapsulation of bioactive compounds using proteins as wall materials has emerged as an effective strategy to enhance their stability, bioavailability, and controlled release. Proteins offer unique functional properties, including amphiphilic behavior, gel-forming ability, and interactions with bioactives, making them ideal candidates for encapsulation. Animal-derived proteins, such as whey and casein, exhibit superior performance in stabilizing lipophilic compounds, whereas plant proteins, including soy and pea protein, demonstrate greater affinity for hydrophilic bioactives. Advances in protein modification and the formation of protein–polysaccharide complexes have further improved encapsulation efficiency, particularly for heat- and pH-sensitive compounds. This review explores the physicochemical characteristics of proteins used in encapsulation, the interactions between proteins and bioactives, and the main encapsulation techniques, including spray drying, complex coacervation, nanoemulsions, and electrospinning. Furthermore, the potential applications of encapsulated bioactives in functional foods, pharmaceuticals, and nutraceuticals are discussed, highlighting the role of emerging technologies in optimizing delivery systems. Understanding the synergy between proteins, bioactives, and encapsulation methods is essential for developing more stable, bioavailable, and sustainable functional products. Full article

Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics are widely known for their positive outcomes on multiple cancers, including BC. The current study investigates the suppressive effects of individual and combined EVOO phenolics for BC progression and motility. Screening of a small library of EVOO phenolics at a single dose of 10 µM against the viability of the BC cell lines ZR-75-1 (luminal A) and MDA-MB-231 (triple negative BC, TNBC) identified oleocanthal (OC) and ligstroside aglycone (LA) as the most active hits. Screening of EVOO phenolics for BC cells migration inhibition identified OC, LA, and the EVOO lignans acetoxypinoresinol and pinoresinol as the most active hits. Combination studies of different olive phenolics showed that OC combined with LA had the best synergistic inhibitory effects against the TNBC MDA-MB-231 cells migration. A combination of 5 µM of each of OC and LA potently suppressed the migration and invasion of the MDA-MB-231 cells versus LA and OC individual therapies and vehicle control (VC). Animal studies using the ZR-75-1 BC cells orthotopic xenografting model in female nude mice showed significant tumor progression suppression by the combined OC-LA, 5 mg/kg each, ip, 3X/week treatments compared to individual LA and OC treatments and VC. The BC suppressive effects of the OC-LA combination were associated with the modulation of SMYD2–EZH2–STAT3 signaling pathway. A metastasis–clonogenicity animal study model using female nude mice subjected to tail vein injection of MDA-MB-231-Luc TNBC cells also revealed the effective synergy of the combined OC-LA, 5 mg/kg each, compared to their individual therapies and VC. Thus, EVOO cultivars rich in OC with optimal LA content can be useful nutraceuticals for invasive hormone-dependent BC and TNBC progression and metastasis. Full article

This study links the traditional use of celery (Apium graveolens L.) and parsley (Petroselinum crispum L.) roots in Balkan cuisine and herbal medicine, along with the longstanding role of turmeric (Curcuma longa L.) rhizome in Ayurvedic and Asian medicinal practices, with modern technological approaches to develop a functional food formulation. A series of blend variations were evaluated for total phenolic content, antioxidant capacity, and sensory quality. The incorporation of turmeric significantly enhanced the antioxidant potential of celery–parsley mixtures. Celery–parsley–turmeric root blend (CPT6), comprising equal parts, was identified as optimal, exhibiting high total phenolic content (9.56 mg gallic acid equivalent/g), strong antioxidant activities, and a favourable sensory profile rated as “very good” (3.58 average score). CPT6 further demonstrated promising biofunctional properties, including potent α-amylase and α-glucosidase inhibition activities (72% and 80%, respectively), alongside moderate antihypertension activity (ACE) (62%) and hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibition (55%). Chemometric analyses (PCA) and machine learning modelling (ANN) confirmed the significant role of turmeric proportion in enhancing both bioactivity and consumer acceptability. This research highlights the synergy between tradition and technology in creating novel, multifunctional food ingredients suited for functional food and nutraceutical applications. Full article

Background/Objectives: Rhodesain is a cysteine protease crucial for the life cycle of Trypanosoma brucei rhodesiense, a parasite that causes the lethal form of human African trypanosomiasis. For these reasons, rhodesain is considered an important target for the drug discovery process of novel antitrypanosomal agents. Methods: In the present work, we carried out a combination study of two novel synthetic nitriles, Nitrile 1 and Nitrile 2, with curcumin, the golden multitarget nutraceutical obtained from Curcuma longa L., which we demonstrated to inhibit rhodesain in a non-competitive manner. We calculated the combination index (CI) in both the combination studies by using the Chou and Talalay method. Results: Comparing the CI values of the combinations Nitrile 1 + curcumin and Nitrile 2 + curcumin, we assessed that the inhibitory effect of the combination Nitrile 2 + curcumin against rhodesain was much more potent than that of the other combination. At the IC₅₀ value, in the case of the combination Nitrile 1 + curcumin an additive effect occurred, while in the case of Nitrile 2 + curcumin, we observed a moderate synergism: at 99% of the effect, the synergism induced by the combination Nitrile 2 + curcumin was much stronger than the synergism promoted by the combination Nitrile 1 + curcumin (CI = 0.3843 vs 0.6622, respectively). Conclusions: The co-administration of dipeptide nitriles with curcumin enhances rhodesain inhibition through synergistic effects. Notably, Nitrile 2 + curcumin exhibits a stronger synergy at higher inhibition levels, indicating a greater therapeutic potential. Full article

This study evaluated the impact of the food matrix on the bioaccessibility and hypoglycemic potential and antioxidant potential of betalains from red prickly pear juice (Opuntia spp.) after in vitro gastrointestinal digestion. Six aqueous model systems (AMSs) were formulated using a betalain extract combined with glucose, citric acid, mucilage, pectin, or all components, alongside three complex matrices, the fresh juice (FJ), a formulated beverage (BF), and a pasteurized formulated beverage (BP). In vitro digestion simulated the gastric and intestinal phases. The results showed that complex matrices (FJ, BF, and BP) enhanced betalain bioaccessibility, with FJ exhibiting the highest bioaccessibility (59%). Mucilage and pectin provided the strongest protection, reducing betalain degradation by 30% and 25%, respectively, while citric acid had a destabilizing effect. Pasteurization (BP) reduced betalain stability compared to FJ and BF. Antioxidant activity decreased post-digestion but remained higher in BF. Notably, FJ showed the highest inhibition of α-amylase (72%) and α-glucosidase (68%), surpassing acarbose (50–60% inhibition). These findings highlight the critical role of the food matrix, particularly mucilage and pectin, in stabilizing betalains through non-covalent interactions and enhancing their hypoglycemic potential. Red prickly pear juice emerges as a promising functional food for managing postprandial glucose levels, offering valuable insights for developing betalain-rich foods to address type 2 diabetes. Full article

Nitraria sibirica Pall., a halophytic shrub native to arid and saline–alkaline ecosystems, represents a dual-purpose resource for ecological stabilization and functional food development. This review synthesizes current knowledge of its bioactive compounds and pharmacological properties, while identifying research gaps in stress-induced metabolic regulation. The plant contains diverse phytochemicals including phenolic glycosides (e.g., clovin), alkaloids (e.g., nitraramine), immunomodulatory polysaccharides, and anthocyanins, which collectively demonstrate superior antioxidant capacity (freeze-dried polysaccharides outperform Butylated Hydroxytoluene (BHT)), significant antihypertensive effects via angiotensin-converting enzyme (ACE) inhibition and nitric oxide (NO) pathway activation, and broad-spectrum antimicrobial activity against foodborne pathogens. Notably, its pectin components reduce allergen absorption by 72%, suggesting potential as hypoallergenic food additives. These findings validate traditional medicinal uses while revealing novel applications in functional foods and nutraceuticals. Despite promising preclinical results, key challenges remain in understanding compound synergies under environmental stress and translating findings to human applications. Future research should employ multi-omics approaches to elucidate stress-adaptive phytochemical biosynthesis, coupled with clinical validation and sustainable cultivation methods. As a model species for ecological and nutritional applications, N. sibirica offers innovative solutions for addressing both global health challenges (metabolic disorders) and environmental concerns (soil rehabilitation), positioning it at the forefront of climate-resilient agricultural innovation. Full article

Rice bran, a major byproduct of rice processing, is rich in unsaturated fatty acids, high-quality proteins, and bioactive compounds such as γ-oryzanol and ferulic acid. However, its poor storage stability and susceptibility to hydrolytic and oxidative rancidity critically limit industrial exploitation. Recent advances in non-thermal stabilization technologies—valued for their energy efficiency, scalability, and nutrient preservation—offer promising solutions. This review systematically elucidates the enzymatic and microbial mechanisms driving bran rancidity, emphasizing lipase and lipoxygenase activity, and critically evaluates the efficacy of emerging non-thermal strategies. Key findings highlight the superiority of non-thermal methods: cold plasma reduces lipase activity by 70% within 5 min via reactive oxygen species-induced structural disruption; ultra-high pressure preserves 95% of γ-oryzanol by selectively breaking hydrogen bonds in enzymes; high-energy electron beam irradiation suppresses rancidity markers by 45–78%; and enzymatic stabilization with immobilized papain achieves 78% lipase inactivation while retaining <5% nutrient loss. Compared to thermal approaches, non-thermal technologies enhance bioactive retention, while extending shelf-life by 2–3 weeks. By addressing challenges such as microbial synergy, parameter optimization, and industrial scalability, this review provides actionable insights for deploying green, energy-efficient strategies to valorize rice bran into functional foods and nutraceuticals, aligning with global demands for sustainable ingredient innovation. Full article

This study explores the development and characterization of lipid nanostructures (NLCs) containing natural deep eutectic solvents (NaDESs) derived from taperebá peel extract (Spondias mombin), a by-product rich in bioactive phenolic compounds, including ellagic acid and quercetin. The taperebá extract exhibited a high polyphenol content (2623 mg GAE/L) and notable antioxidant activity, as demonstrated by DPPH (258 mM TEAC/100 mL) and ABTS (495 mM TEAC/100 mL) assays. NLCs were developed using NaDESs to enhance the stability and bioavailability of the antioxidant compounds. Physicochemical characterization confirmed the formation of stable, nanometric, and monodispersed formulations with efficient encapsulation. Biological evaluation of the NLC-TAP-NaDES formulation demonstrated its remarkable capacity to mitigate oxidative stress in cells subjected to H₂O₂-induced ROS generation. Fluorescence imaging revealed a significant reduction in intracellular ROS levels in treated cells compared to untreated controls, confirming the antioxidant efficacy of the formulation. This outcome underscores the synergy between NaDESs and NLC systems in protecting and delivering phenolic compounds. This study highlights the potential of utilizing underexplored by-products, such as taperebá peels, to develop sustainable and effective antioxidant delivery systems. The NLC-TAP-NaDES platform combines nanotechnology with green chemistry principles, presenting significant implications for the treatment of oxidative stress-related conditions and broader applications in pharmaceutical and nutraceutical sciences. These findings contribute to advancing sustainable innovations in antioxidant therapies, leveraging the dual benefits of bioeconomy and high-performance nanomaterials. Full article

Glioblastoma (GBL) is one of the more malignant primary brain tumors; it is currently treated by a multimodality strategy including surgery, and radio- and chemotherapy, mainly consisting of temozolomide (TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival time of <2 years. The identification of natural molecules with strong anti-tumor activity led to the combination of these compounds with conventional chemotherapeutic agents, developing protocols for integrated anticancer therapies. Curcumin (CUR), resveratrol (RES), and its glucoside polydatin (PLD) are widely employed in the pharmaceutical and nutraceutical fields, and several studies have demonstrated that the combination of these natural products was more cytotoxic than the individual compounds alone against different cancers. Some of us recently demonstrated the synergistic efficacy of the sublingual administration of a new nutraceutical formulation of CUR+PLD in reducing tumor size and improving GBL patient survival. To provide some experimental evidence to reinforce these clinical results, we investigated if pretreatment with a combination of CUR+PLD can improve TMZ cytotoxicity on GBL cells by analyzing the effects on cell cycle, viability, morphology, expression of proteins related to cell proliferation, differentiation, apoptosis or autophagy, and the actin network. Cell viability was assessed using the MTT assay or a CytoSmart cell counter. CalcuSyn software was used to study the CUR+PLD synergism. The morphology was evaluated by optical and scanning electron microscopy, and protein expression was analyzed by Western blot. Flow cytometry was used for the cell cycle, autophagic flux, and apoptosis analyses. The results provide evidence that CUR and PLD, acting in synergy with each other, strongly improve the efficacy of alkylating anti-tumor agents such as TMZ on drug-resistant GBL cells through their ability to affect survival, differentiation, and tumor invasiveness. Full article

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. Full article

Berberine (BBR) and silymarin (SM) are natural compounds extracted from plants known for their antioxidant and chemoprotective effects on the liver. The present study aimed to investigate the beneficial properties of BBR and SM and the association of BBR with SM on liver function using fish as “in vivo” models. Moreover, the study investigated their hepatoprotective role after acetaminophen (APAP) exposure. For this purpose, the fish (N = 360; 118.4 ± 11.09 g) were fed with control or experimental diets for 9 weeks. In the experimental diets, the feed was supplemented with either SM (1 g/kg feed), BBR (100 and 200 mg/kg feed), or a combination of BBR with SM (SM 1 g/kg feed + BBR 100 mg/kg feed and, respectively, SM 1 g/kg feed + BBR 200 mg/kg feed). After the feeding trial, seven fish from each tank were randomly selected and exposed to a single APAP dose. The selected serum biochemical markers, oxidative stress markers, and lysozyme activity were used to evaluate the efficiency of the supplements on carp’s health profile, particularly regarding the hepatopancreas function. Our results showed that the inclusion of SM and BBR (either as a single or in combination) reduced the serum contents of total cholesterol, triglyceride, and alanine transaminase. An increase in the high-density cholesterol was observed after the administration of BBR or BBR in association with SM. Both supplements showed hepatoprotective activity against APAP-induced hepatotoxicity, especially BBR. The ameliorative effects of SM (1 g) in association with BBR (100 mg) were highlighted by the modulation of the nonspecific immune system and oxidative stress alleviation after APAP exposure. Full article

Nano-range bioactive colloidal carrier systems are envisaged to overcome the challenges associated with treatments of numerous diseases. Lipid nanoparticles (LNPs), one of the extensively investigated drug delivery systems, not only improve pharmacokinetic parameters, transportation, and chemical stability of encapsulated compounds but also provide efficient targeting and reduce the risk of toxicity. Over the last decades, nature-derived polyphenols, vitamins, antioxidants, dietary supplements, and herbs have received more attention due to their remarkable biological and pharmacological health and medical benefits. However, their poor aqueous solubility, compromised stability, insufficient absorption, and accelerated elimination impede research in the nutraceutical sector. Owing to the possibilities offered by various LNPs, their ability to accommodate both hydrophilic and hydrophobic molecules and the availability of various preparation methods suitable for sensitive molecules, loading natural fragile molecules into LNPs offers a promising solution. The primary objective of this work is to explore the synergy between nature and nanotechnology, encompassing a wide range of research aimed at encapsulating natural therapeutic molecules within LNPs. Full article

Despite the wide pharmacological action of polyphenols, their usefulness is limited due to their low oral bioavailability, which is due to their low solubility and rapid first-pass metabolism. Red vine leaf extract is an herbal medicine containing several polyphenols, with resveratrol and polydatin as the main compounds exhibiting antioxidant and anti-inflammatory properties. In the first stage of the work, using the Design of Experiment (DoE) approach, the red vine leaf extract (50% methanol, temperature 70 °C, and three cycles per 60 min) was obtained, which showed optimal antioxidant and anti-inflammatory properties. In order to circumvent the above-described limitations and use innovative technology, electrospun nanofibers containing the red vine leaf extract, polyvinylpyrrolidone (PVP), and hydroxypropyl-β-cyclodextrin (HPβCD) were first developed. The optimization of the process involved the time of system mixing prior to electrospinning, the mixture flow rate, and the rotation speed of the collector. Dissolution studies of nanofibers showed improved resveratrol release from the nanofibers (over five-fold). Additionally, a PAMPA-GIT assay confirmed significantly better buccal penetration of resveratrol from this nanofiber combination (over ten-fold). The proposed strategy for electrospun nanofibers with the red vine leaf extract is an innovative approach to better use the synergy of the biological action of active compounds present in extracts that are beneficial for the development of nutraceuticals. Full article