Search Results (967)

The human gut microbiota represents a complex and dynamic ecosystem of trillions of microorganisms that play a fundamental role in maintaining physiological homeostasis, regulating metabolism, and modulating the immune system. This narrative review explores the biochemical intricacies of the gut microbiome, focusing on the dominant phyla (Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia, Fusobacteria) and their specific contributions to host health. A critical emphasis is placed on the metabolic outputs of these microorganisms, such as short-chain fatty acids (SCFAs) like butyrate, which serve as vital energy sources and anti-inflammatory signaling molecules. Conversely, the review examines how dysbiosis, the disruption of microbial balance, is mechanistically linked to the pathogenesis of diverse conditions, including obesity, diabetes mellitus, inflammatory bowel disease (IBD), and gout. Furthermore, it highlights the profound impact of dietary interventions on microbial architecture, notably, how non-digestible carbohydrates promote beneficial taxa and eubiosis, while high-fat and high-sugar diets drive metabolic endotoxemia and systemic inflammation. By synthesizing current knowledge on microbial biotransformations of proteins and polyphenols, this work underscores the bidirectional relationship between nutrition and the microbiome. Ultimately, understanding these biochemical interactions is essential for developing targeted probiotic, prebiotic, and nutritional strategies to prevent and manage chronic metabolic and inflammatory disorders. Full article

ZnO can be easily obtained using different salts as precursors, and many examples are present in the literature describing the effect of several additives in the synthesis. In this paper, we study the effects of the addition of polyphenols present in the residues of the wine supply chain. The polyphenols are extracted from grape pomace and fractionated, exploiting a membrane-based process equipped with polysulfone ultrafiltration membranes (cut-off 1 kDa and 5 kDa) that can separate the plethora of molecules into larger than 5 kDa and smaller than 1 kDa. The extract and its fractions after the ultrafiltration process were used as additives for the thermal precipitation synthesis of ZnO from Zn acetate. The chemical and physical properties were studied with the aim of understanding the characteristics that influence the activity of the photocatalysts. To this purpose, a commercial system was used for comparison, and the photoactivity was analyzed with a caffeine solution upon irradiation, exploiting the UVA and VIS electromagnetic radiation for the activation of the catalytic materials. The kind of polyphenol fraction affects the surface behaviors of the nanoparticles. Morphology, presence of trapped hole/electron centers, and acidity/basicity of the surface sites of ZnO appear to be the most relevant features in the efficiency towards caffeine degradation. Full article

Adolescence is a metabolically vulnerable period, during which rapid physiological maturation coincides with the dynamic remodelling of the gut microbiome. This narrative review summarises evidence from 2015 to 2025 to clarify how disturbances to the gut–liver axis driven by dysbiosis contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD) in young people. Based on a systematic search of the databases PubMed, Scopus and Web of Science, we outline the basis of bidirectional communication between the gut and liver and emphasise how microbial imbalance alters the handling of lipids in the liver by enhancing de novo lipogenesis, impairing fatty acid oxidation and disrupting AMPK signalling and mitochondrial function. Consistent findings from clinical and experimental studies show that adolescents with NAFLD exhibit reduced microbial diversity, the enrichment of ethanol- and LPS-producing taxa, and altered short-chain fatty acid profiles. Each of these is associated with hepatic inflammation and metabolic reprogramming. Microbial molecules, including LPS, secondary bile acids and branched-chain amino acid metabolites, activate TLR4–NF-κB pathways, promote Kupffer cell activation and intensify oxidative stress. These mechanisms intersect with factors specific to adolescence, such as increased adiposity, hormonal shifts and diet-induced metabolic strain. Dietary patterns emerge as key modulators of these processes. Westernised diets promote dysbiosis and endotoxemia, whereas Mediterranean, fibre-rich and plant-based diets enhance SCFA production, strengthen epithelial integrity and modulate adiponectin-dependent hepatic metabolism. Micronutrient-sensitive epigenetic regulation, particularly that involving folate, choline and polyphenols, also plays a role in shaping lipid homeostasis and inflammatory tone. We also highlight emerging evidence that the activation of cytoprotective pathways, especially Nrf2, is dependent on lifestyle factors and links antioxidant-rich functional foods and physical activity to improved mitochondrial resilience and microbiome stability. We evaluate therapies targeting the microbiome, including probiotics, prebiotics, synbiotics and postbiotics, which reduce endotoxemia, restore microbial balance and complement dietary strategies. Thus, these findings emphasise the importance of age-specific, mechanistically informed interventions that integrate diet quality, microbial ecology, and the molecular pathways that govern metabolic health in adolescents with NAFLD. Full article

Allergic rhinitis (AR) and allergic asthma are chronic airway inflammatory diseases characterized by three phases: sensitization, acute exacerbation, and chronic remodeling. While conventional antiallergic drugs provide symptomatic relief, they often face limitations including drug resistance, side effects, and inability to reverse chronic airway remodeling. Natural products have emerged as promising therapeutic alternatives due to their multi-target effects and safety profiles. This review systematically summarizes natural small molecules targeting distinct pathological mechanisms across the three phases of AR and asthma, introducing a chronopharmacological perspective for stage-specific therapeutic strategies. During sensitization, flavonoids (quercetin, luteolin, apigenin, baicalin) and polyphenols (curcumin, resveratrol) target the epithelial–dendritic cell axis by suppressing alarmin release and blocking dendritic cell maturation. In acute exacerbation, flavonoids (hispidulin, quercetin) and isoquinoline alkaloids (coptisine) exhibit rapid intervention through mast cell stabilization and neurogenic inflammation suppression. In chronic remodeling, stilbenes (resveratrol) and flavones (baicalin, baicalein) reverse established structural changes through TGF-β1/Smad, PTEN/PI3K/AKT, and PDGF-BB/PDGFR-β pathways. Mapping natural compounds to specific disease stages provides a molecular basis for precision medicine approaches. Full article

Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent, but its clinical utility is limited by oxidative stress-mediated renal toxicity. This study evaluated the nephroprotective potential of the dietary polyphenolic bioactive molecule piceatannol (PIC) in its crude and liposomal nanoparticle (PIC-LNP) forms against MTX-induced kidney injury in rats. Sixty rats were allocated into six groups and received vehicle, PIC, PIC-LNPs, MTX, or combinations of MTX with PIC or PIC-LNPs. MTX administration induced marked renal dysfunction and oxidative/nitrosative stress, reflected by elevated serum urea, creatinine, and uric acid, together with increased renal ROS, MDA, protein carbonyls, 8-OHdG, and nitric oxide, in parallel with suppression of the Nrf2/HO-1 antioxidant pathway. These disturbances were accompanied by activation of TLR4/NF-κB and MAPK signaling, upregulation of pro-inflammatory cytokines, and a shift toward apoptosis, as evidenced by increased Bax and caspase-3 and reduced Bcl-2 expression. Histological and ultrastructural analyses confirmed extensive glomerular and tubular damage with mitochondrial disruption and cytoplasmic vacuolations. PIC treatment attenuated these MTX-induced alterations, whereas the liposomal formulation conferred superior protection. PIC-LNPs restored Nrf2/HO-1 signaling, enhanced endogenous antioxidant defenses, reduced oxidative/nitrosative and inflammatory responses, and normalized apoptotic markers, accompanied by substantial preservation of renal architecture and cellular integrity. Immunohistochemistry demonstrated strong Nrf2 expression with minimal NF-κB activation in the PIC-LNP group. Collectively, these findings highlight liposomal piceatannol as a promising bioactive-molecule-based strategy for controlling oxidative stress and mitigating chemotherapy-associated oxidative-stress-related renal injury. Full article

Triple-negative breast cancer represents one of the most aggressive and therapeutically challenging subtypes of breast malignancies, characterized by marked biological heterogeneity, rapid progression, and limited targeted treatment options. Conventional therapies are frequently constrained by drug resistance, systemic toxicity, and high rates of recurrence. In this context, natural products have gained increasing attention as multifunctional agents capable of modulating several hallmarks of triple-negative breast cancer. Bioactive compounds, including polyphenols, terpenoids, alkaloids, and marine-derived molecules, exhibit pleiotropic antitumor effects by interfering with key oncogenic pathways. Importantly, these compounds have demonstrated the ability to counteract major mechanisms of therapeutic resistance, modulate the tumor immune microenvironment, and enhance the efficacy of standard chemotherapy and immunotherapy. Advances in drug delivery strategies, such as nanoparticle-based systems and tumor-targeted formulations, together with patient-specific molecular profiling, further expand the potential of these agents within personalized treatment approaches. This narrative review critically examines the role of natural compounds in targeting the hallmarks of triple-negative breast cancer and their potential synergistic use to improve therapeutic efficacy while reducing treatment-related toxicity. Overall, the integration of natural product-based strategies into precision oncology frameworks may offer more effective, less toxic, and individualized therapeutic options for this aggressive breast cancer subtype. Full article

The synergistic effects of glucose (Glu) concentration and clay mineral type (kaolinite [Kao], montmorillonite [Mon]) on abiotic humification via the polyphenol-Maillard reaction remain poorly understood. To address these scientific challenges, a series of controlled, sterile batch experiments was conducted. Specifically, a glucose concentration gradient (0, 0.03, 0.06, 0.12, and 0.24 mol/L) was established; Kao and Mon were separately introduced as mineral catalysts; and the Maillard reaction was facilitated in the presence of catechol and glycine under strictly abiotic conditions to preclude any potential biological interference. Comprehensive analyses were performed on the reaction products—namely, the supernatant and the dark-brown residue generated during the reaction process. These analyses included: the E₄/E₆ ratio and total organic carbon (TOC) content of the supernatant; the carbon-based ratio of humic-like acid to fulvic-like acid (C_HLA/C_FLA); and the structural characteristics of humic-like acid (HLA) isolated from the dark-brown residue. Results showed dynamic E₄/E₆ ratio and TOC changes in the supernatant were accurately described by the Logistic function. Kao favored soluble organic C accumulation and enhanced retention of early-stage, low-molecular-weight intermediates in the dark-brown residue, while Mon promoted humic-like substances (HLS) polymerization and aromatic condensation. FTIR spectroscopy analysis identified optimal Glu thresholds for maximal HLS formation—0.03 mol/L for Kao and 0.06 mol/L for Mon—indicating non-linear, rather than monotonic, dependence on Glu dosage. Comparative pre- and post-reaction Fourier-transform infrared (FTIR) spectroscopy further demonstrated that Mon, owing to Mg–OH octahedral sites arising from isomorphic substitution, formed more stable Cat chelates than Kao. These chelates effectively stabilized surface-bound hydroxyl-associated water molecules and modulated the electron cloud distribution around Si–O bonds. Collectively, this study clarified the dual regulatory role of Glu concentration and clay mineral identity in abiotic humification pathways, advanced mechanistic understanding of clay mineral-mediated polyphenol-Maillard reactions, and established a scientific foundation for optimizing humification efficiency in both engineered and natural systems. Full article

Antimicrobial resistance (AMR) is one of the most pressing global public health challenges, compromising the effectiveness of standard antibiotic therapies and increasing morbidity, mortality, and healthcare costs. The scarcity of new antibiotics has driven research into alternative strategies to restore or enhance the effectiveness of existing drugs. Natural compounds, including polyphenols, alkaloids, terpenes and terpenoids, antimicrobial peptides, and microbial secondary metabolites, exhibit multitarget activities such as membrane disruption, efflux pump inhibition, biofilm suppression, and quorum sensing interference. In parallel, synthetic and semi-synthetic small-molecule inhibitors have been rationally designed to target specific resistance determinants, including β-lactamases, efflux systems, quorum sensing pathways, and stress-induced mutagenesis mechanisms such as the SOS response and DNA repair processes. These agents act as adjuvants, restoring susceptibility or reducing bacterial virulence without exerting strong selective pressure. The integration of natural bioactive compounds and targeted small-molecule inhibitors represents a promising complementary strategy for conventional antibiotics. Further pharmacological and clinical investigations are required to translate these approaches into effective tools within antimicrobial stewardship programs and broader public health strategies aimed at mitigating the global burden of AMR. This narrative review analyses the recent literature on natural compounds and synthetic or semi-synthetic small-molecule inhibitors with documented activity against antimicrobial resistance mechanisms. Full article

To investigate the effect of phenolic hydroxyl group number on the interaction between catechins and a plant-derived protein carrier, four catechins with varying hydroxyl numbers—epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG)—were investigated. The new plant-derived edible dock protein (EDP) was selected as a carrier matrix. EDP, when employed as a protein delivery carrier, possessed a hydrophobic amino acid content of 45%. This structural feature enabled it to provide more hydrophobic cavities for small molecule compounds, thereby facilitating better binding with them. The results indicated that the order of loading capacity of catechins within EDP was EGCG (9.7%) > ECG (9.1%) > EGC (8.8%) > EC (7.1%). This sequence was consistent with the number of hydroxyl groups in catechin: EGCG (8) > ECG (7) > EGC (6) > EC (5). Among the four catechins, EGCG had the highest binding constant (Ka = 2.6 × 10³ L/mol), leading to the largest quenching of EDP. During self-assembly, hydrogen bonding, hydrophobic and electrostatic interactions were the main driving forces, and the interaction between EGCG and EDP was the strongest. This study indicated that the hydroxyl group number of polyphenolic compounds can determine its binding affinity with proteins. Full article

This study examined the evolution of volatile and non-volatile compounds of a Cypriot monovarietal cultivar Maratheftiko red wine over a span of six years (2019–2024). Several physicochemical properties of the wines were evaluated. Alcohol content and volatile acidity remained stable; acidity and malic acid are the main differentiating factors among vintages. In addition, bioactive molecules in the wines showed a distinct vintage effect, with the 2024 vintage exhibiting significantly higher concentrations. For instance, the high concentration of polyphenols (3877.86 mg gallic acid equivalents per L), tannins (688.43 mg of catechin equivalents per L), flavonoids (506.90 mg of rutin equivalents per L), and anthocyanins (413.74 mg of cyanidin equivalents per L) contributed to the high antioxidant capacity of the specific vintage, as FRAP and DPPH assays were measured at 44.60 and 29.91 mmol of ascorbic acid equivalents per L, respectively. Furthermore, the intense crimson color of this red wine could be attributed to the high concentration of the abundant anthocyanin malvidin-3-O-glucoside in this vintage (21.62 mg/L). On the other hand, it was observed that the latest vintage showed high polyphenol concentration but low volatile compound concentration. This pattern was ascertained through correlation analyses and could be attributed to an unsatisfactory level of the aging process. Correlation analysis (Pearson’s r) confirmed inverse relationships between polyphenol concentration and volatile compounds (r = −0.62, p < 0.05). Principal component analysis (PCA) further highlighted the 2024 as an outlier vintage, distinguished by elevated phenolic and antioxidant profiles. Full article

Central nervous system disorders drive disability, yet many neuroactive candidates fail because the brain is a hard compartment to dose. Plant-derived molecules spanning polyphenols, alkaloids, terpenoids, and cannabinoids are attractive because their pleiotropic actions can engage oxidative stress, neuroinflammation, and circuit dysfunction. In practice, the blood–brain barrier (BBB) restricts most native phytochemicals through tight-junction selectivity, rapid metabolism, low solubility, and transporter-mediated efflux. Key gaps include poor standardization of exposure metrics, limited human-relevant BBB models, and few head-to-head studies that compare delivery platforms on the same payload and outcome. This review tackles the mismatch between mechanistic promise and reliable brain exposure that stalls translation. The objectives are to link phytochemical liabilities to enabling strategies in nanomedicine, alternative routes, and transporter-targeted prodrugs, and to propose decision-grade endpoints for translation. We synthesize evidence on BBB transport logic, nanocarrier families, targeting ligands, intranasal delivery, focused ultrasound-mediated opening, and prodrug approaches that hijack influx transporters, while foregrounding safety and chemistry, manufacturing, and controls (CMC) constraints. Here we highlight that effective neurotherapeutics emerge when chemistry, carrier, route, and measurement are co-designed rather than optimized in isolation. This framework can guide platform selection, de-risk first in-human studies, and sharpen trial endpoints. More broadly, it offers a transferable playbook for barrier-limited drug development across neurology, psychiatry, and oncology. Full article

Polyphenols are a diverse class of bioactive phytochemicals increasingly recognized for their ability to modulate human physiology through extensive interactions with the gut microbiota. This review provides a comprehensive and updated synthesis of the bidirectional polyphenol–microbiota relationship, emphasizing how dietary polyphenols reshape microbial community structure while intestinal microorganisms metabolize polyphenols into smaller, more bioavailable derivatives. These microbial metabolites—such as urolithins, phenolic acids, and dihydroresveratrol—exert amplified biological activities compared to their parent molecules, acting on key molecular pathways linked to oxidative stress, inflammation, energy homeostasis, and metabolic regulation. Through integration of mechanistic studies, multi-omics analyses, and emerging clinical evidence, this review outlines the potential of the polyphenol–microbiota–metabolite axis as a target for precision nutrition and microbiota-informed therapeutic interventions. The manuscript highlights ongoing challenges, including inter-individual variability in polyphenol metabolism, and proposes future research directions to advance the field of personalized nutrition. Full article

Functional foods are a central paradigm in modern nutrition science, acting as effective vehicles for the delivery of bioactive compounds that link conventional nutrition and preventive medicine. Beyond their basic nutritional role, these foods are specifically designed or naturally enriched to convey biologically active constituents capable of modulating physiological functions and reducing the risk of chronic diseases, thereby supporting long-term health maintenance. The chemical composition of functional foods—including polyphenols, phytosterols, vitamins and dietary fibers—underlies their capacity to act as matrices that protect, transport, and enhance the bioavailability of bioactive molecules. This review provides an integrated nutritional perspective on functional foods, with particular emphasis on their role as delivery systems for health-promoting compounds. The molecular mechanisms by which food bioactives interact with cellular and molecular targets, regulate oxidative stress and inflammation, and modulate metabolic and immune pathways are critically discussed. Special attention is devoted to redox-active bioactives, the structural diversity and bioavailability of polyphenols, the cholesterol-lowering properties of phytosterols, the physiological relevance of fat- and water-soluble vitamins, and the complex interactions between functional foods, gut microbiota, prebiotics, probiotics, and dietary fibers. Overall, this review aims to provide a comprehensive scientific framework for understanding how functional foods can be strategically engineered and utilized as bioactive compound vehicles in health promotion and disease prevention. Full article

Adolescence represents a critical window of metabolic plasticity, during which profound hormonal, neurobiological, and physiological remodelling increases susceptibility to nutritional exposures. In parallel with the rising prevalence of obesity, insulin resistance, metabolic syndrome, and non-alcoholic fatty liver disease among young people, there is growing interest in the potential for functional food components to modulate epigenetic pathways that govern metabolic programming. This narrative review synthesises current evidence (2015–2025) from PubMed, Scopus, Web of Science, and Embase to elucidate how diet-derived bioactive compounds influence epigenetic regulation relevant to adipogenesis, appetite control, insulin signalling, and lipid homeostasis during adolescence. Particular emphasis is placed on molecular mechanisms, including DNA methylation changes in genes regulating adipocyte differentiation, hypothalamic neuropeptide expression, and pancreatic β-cell function; histone modifications, such as acetylation and methylation events that remodel chromatin accessibility in metabolic tissues; and modulation of microRNA networks implicated in lipid metabolism, inflammatory signalling, and insulin secretion. Furthermore, the review examines the interplay between diet, the gut microbiota, and the epigenome, highlighting the role of microbially derived short-chain fatty acids (SCFAs) as endogenous histone deacetylase inhibitors and mediators of epigenetic remodelling in adipose tissue. By linking these mechanisms to specific functional food components, including polyphenols, long-chain omega-3 fatty acids, fermentable dietary fibre, and other bioactive molecules, we demonstrate how nutritional signals can counteract maladaptive metabolic trajectories and potentially reduce the intergenerational transmission of metabolic risk. A deeper understanding of these epigenetic effects provides the foundation for developing personalised nutrition strategies aimed at preventing metabolic disorders from emerging during adolescence and beyond. Full article

The surplus in the production of buffalo milk determines the possibility of finding alternative solutions for its use. Indeed, the utilization of milk in cosmetic formulations has been met with great approval by consumers, primarily due to its highly appreciated emollient characteristics. The aim of this research was to test an alternative use of buffalo milk in the production of artisanal solid soaps, using buffalo milk as raw material and Lavender, Thyme, and Grape pomace as sources of natural bioactive compounds. The analytical approach was focused on using vegetable materials in three forms: fresh, dried, and freeze-dried. For this purpose, the chemical features of both raw materials and artisanal soaps were determined in order to understand the feasibility of these productions. All formulated artisanal soaps revealed good chemical characteristics, such as a low moisture content, and got high scores in the sensory evaluation, with those with Lavender and Grape pomace being the most appreciated formulations. Furthermore, adding vegetable materials increased the bioactive molecules content, as demonstrated by the data obtained from total polyphenol content and antioxidant activity. Therefore, the addition of plants and vegetables to the formulation could represent an innovative production of natural soaps and be a further element for the market trends. Full article