Search Results (2,794)

Methicillin-resistant Staphylococcus aureus (MRSA) is a major clinical problem due to its resistance, virulence, and biofilm formation, which diminish antibiotic efficacy. This review explores natural products and antimicrobial nanoparticles (NPs) as alternative and combined strategies for controlling MRSA. Natural compounds, such as plant metabolites, essential oils, antimicrobial peptides, and fungal products, act by disrupting membranes, interfering with cellular processes, and limiting biofilm formation. Antimicrobial NPs, especially metal and metal oxide materials, act through membrane damage, oxidative stress, and metal ion release, enabling activity against resistant bacteria and improving biofilm penetration. Combining natural products with NPs increases stability, delivery, and local activity, enhances antibacterial effects, and reduces effective doses. Green synthesis enables direct integration of bioactive compounds, while nano-delivery platforms optimize solubility and controlled release. Nanotechnology-based applications such as wound dressings, nanocarriers, and multifunctional platforms support localized and sustained treatment and promote tissue repair. Despite these advances, clinical use is still constrained by safety concerns, variability in NP properties, and the lack of standardized evaluation and regulatory frameworks. Overall, combining natural products with antimicrobial NPs offers a practical strategy to augment MRSA treatment, but further progress depends on consistent design, robust safety evaluation, and clinical translation. Full article

This study investigates the antioxidant properties of several synthetic peptides derived from milk proteins previously identified in milk permeate, a by-product of the dairy industry. The aim of the research is to identify which peptides present in milk permeate are responsible for its antioxidant activity. A comprehensive experimental strategy was employed to evaluate their antioxidant potential, including in silico selection, in vitro free radical scavenging assays and cellular models using Caco-2 and HCT116 cell lines. The peptides were screened using a molecular docking approach for their potential interaction with the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway, and eight out of twenty-eight were selected and synthesized for further analyses. In vitro, six of the selected peptides demonstrated significant direct antioxidant activity in the DPPH scavenging assay, and two in the ABTS scavenging test. In cellular environments, three peptides (LPAPELGPRQA, LPIIQKLEPQI and NGQVWEESLKRL) effectively protect cells from oxidative stress induced by tert-butyl hydroperoxide, reducing reactive oxygen species production and partially mitigating lipid peroxidation. Further investigation showed that two of them (LPAPELGPRQA and LPIIQKLEPQI) effectively induce the Keap1/Nrf2 pathway, as evidenced by a ∼1.5-fold increase in Nrf2 levels and overexpression of downstream proteins. Permeability studies revealed that these peptides can cross the intestinal monolayer (2–3% in 2 h), suggesting potential systemic effects. Overall, these findings highlight the multifunctional antioxidant properties of the investigated peptides and support their potential application as nutraceuticals or therapeutic agents for oxidative stress-related conditions. Full article

Cyclodepsipeptides constitute a structurally diverse class of natural products composed of amino acid and hydroxy acid residues interconnected through both amide and ester bonds. Among them, xylaroamide A, a cyclic heptadepsipeptide, was recently identified from an endolichenic Xylaria species via a molecular networking-guided discovery approach. Despite xylaroamide A exhibiting intriguing structural features and notable bioactivity potential, its total synthesis has thus far remained unexplored. Herein, we report the first total synthesis of xylaroamide A, achieved through a hybrid solid/solution-phase synthetic approach. The linear precursor was assembled in accordance with the native amino acid sequence via Fmoc-based solid-phase peptide synthesis, incorporating the preassembled ester fragment at a later stage of assembly. Subsequent macrocyclization took place under high-dilution conditions to furnish the target cyclodepsipeptide. The structure of the synthetic product was confirmed by means of optical rotation and NMR and MS spectroscopic analyses, which exhibited good agreement with the reported data for the natural product. This work establishes a reliable and efficient synthetic route to xylaroamide A and provides a foundation for further bioactivity and structure optimization investigations. Full article

Wheat processing generates large volumes of co-products, particularly wheat bran (WB) and wheat germ (WG), which remain underutilized despite their high content of dietary fiber, phenolic compounds, bioactive peptides, and lipophilic antioxidants. Although their composition and processing have been widely investigated, an integrated and application-oriented evaluation of these fractions remains limited. This review provides a structured and critical analysis of WB, raw and defatted WG, and wheat germ oil (WGO), linking composition, processing strategies, and functional performance within a unified framework. Conventional and emerging technologies, including enzymatic hydrolysis, fermentation, thermomechanical treatments, and supercritical CO₂ extraction, are discussed in terms of selectivity, impact on techno-functional properties, and scalability. An evidence-grading approach is introduced to distinguish bioactivities supported by chemical assays, cell-based models, animal studies, or human data, enabling a more rigorous interpretation of health-related effects. Across applications, these co-products have been incorporated into food systems and related sectors, primarily showing improvements in nutritional composition, oxidative stability, and product performance under experimental conditions. However, translation to an industrial scale remains constrained by techno-economic limitations, regulatory requirements, and stability challenges. This work highlights the need for integrated processing strategies aligned with industrial feasibility to support the development of sustainable cereal biorefineries. Full article

Background/Objectives: Native to the Indo-Pacific region, edible bird’s nests (EBN; Yan Wo in Chinese) are the solidified saliva of swiftlets (Aerodramus fuciphagus and A. maximus) and have been consumed as a traditional functional food for centuries. However, the bioactive components and underlying mechanisms of EBN remain poorly understood. EBN consists of over 60% protein, much of which is heavily glycosylated, forming complex glycoconjugates that are resistant to enzymatic digestion. This study examines the properties of EBN-derived bioactive peptides and assesses their potential for skin moisturization and anti-inflammation when applied topically. Methods: EBN was double-boiled for an extended period, then digested with gastric enzymes to extract active peptides. Digestion was over 90% efficient, and peptide molecular weights were measured. The enzymatic digest was then fractionated using an activity-guided approach based on assays for skin moisturization and anti-inflammatory properties. Results: A novel bioactive heptapeptide, with the sequence LAGAAHF and designated EBN_P3, was identified and characterized. It attenuated TNF-α-induced inflammatory responses in HaCaT keratinocytes and alleviated dermatitis symptoms in a DNCB-induced C57BL/6 mouse model. Conclusions: EBN-derived peptides with skin moisturizing and anti-inflammatory activities hold significant promise for development into functional ingredients for skincare products. Full article

Fermented foods and probiotics represent complementary yet distinct components of human nutrition. Fermented foods are shaped by biochemical transformations driven by microbial metabolism, whereas probiotics are live microorganisms that may confer health benefits to the host. In both cases, bacteria, yeasts, and filamentous fungi mediate key metabolic activities that generate bioactive compounds and modulate host–microbiota interactions. During fermentation, microbial communities synthesize organic acids, peptides, exopolysaccharides, vitamins, and other metabolites that enhance food safety, sensory attributes, and potential health-promoting properties. Several microbial products, such as bacteriocins, reuterin, hydroxylated fatty acids, and exopolysaccharides, exhibit antimicrobial, immunomodulatory, antioxidant, and cholesterol-lowering activities. Advancing our understanding of microbial metabolism in fermented foods is essential for developing next-generation functional foods and nutraceuticals that leverage microbial biotransformations to support human health. Nonetheless, multiple challenges limit the translation of these advances into commercial products. Inadequately controlled fermentation may introduce microbiological or chemical hazards, regulatory frameworks governing microbial use in foods remain insufficiently defined, and standardized procedures for microbial strain handling and characterization are still lacking. This narrative review integrates current evidence on the nutraceutical properties of fermented foods and probiotics, while also examining the associated safety considerations and the technological factors that influence fermentation processes. Full article

Background/Objectives: Umami peptides enhance flavor and contribute to appetite regulation (satiety) and metabolic health. By signaling to the orbitofrontal cortex, umami has been shown to improve cognitive function in Alzheimer’s disease dementia. This taste boosts the immune system and induces saliva secretion. However, the molecular mechanisms linking umami peptides to systemic physiology remain poorly understood. This study provides the first integrated analysis of neurological, immunological, and endocrinological pathways activated by umami peptides. Methods: Novel umami peptides were identified using machine-learning and deep-learning analyses from a library of marine-derived bioactive peptides. T1R1-T1R3 heterodimer is the dominant receptor for umami taste transmission in humans, expressed on taste cells, intestinal cells, and hypothalamic tanycytes. Molecular docking confirmed the binding of novel ligands to the T1R1-T1R3 receptor complex. New candidates and experimentally validated umami peptides, identified by sensomics approaches from tauco, chicken soup, pufferfish, and dry-cured ham, were analyzed using gene ontology. Results: The functional enrichment analysis revealed crosstalk among key signaling processes, including glutamatergic and opioidergic pathways. In addition to the role of µ1 opioid receptor (OPRM1), hub gene intersections highlight cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and the anorexigenic pro-opiomelanocortin (POMC) neurons as potential regulators of the gut–brain axis in satiety signaling. Chemokine-encoding genes, melanin-concentrating hormone (MCH), oxytocin (OXT), and neurotensin (NTS) were other key target genes. Conclusions: The identified targets reveal the coordinated crosstalk between peripheral and central umami signaling that may contribute to the regulation of feeding behavior, satiety, cognition, memory, learning, and immune function. These network-based insights generate hypotheses and guide the design of nutritional and drug-like effectors for metabolic and cognitive health. Full article

Natural bioactive polysaccharides have been investigated for their ability to modulate antiviral immune responses. Polysaccharide peptide (PSP) from Coriolus versicolor previously restricted human immunodeficiency virus type 1 (HIV-1) entry into monocytic cells through a protein kinase R (PKR)-dependent cytoskeletal mechanism. However, its impact on antiviral signaling in adaptive cluster of differentiation 4 (CD4)+ T-cell models remains incompletely defined. Here, we evaluated concentration- and time-dependent effects of PSP (50–1000 µg/mL) in Jurkat T cells over 3 and 6 days. Cell viability was assessed by MTT, trypan blue exclusion, and viable cell density analysis. Immunoblotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were performed to examine Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 1 and 2 (STAT1/STAT2), PKR, interferon gamma (IFN-γ), and cofilin-1 signaling. PSP did not induce cytotoxicity at any concentration. Instead, PSP promoted dose- and time-dependent upregulation of intracellular TLR4, PKR, phospho-PKR (Thr446), Cofilin-1, phospho-Cofilin-1 (Ser3), phospho-STAT1 (Tyr701), phospho-STAT2 (Tyr690), phospho-NF-κB (Ser536), and IFN-γ, with amplified responses at Day 6. These changes were paralleled by transcriptional induction of antiviral-associated genes. Collectively, PSP induces coordinated interferon (IFN)-associated and cytoskeletal regulatory signaling in Jurkat T cells without cytotoxicity, providing a mechanistic framework for future evaluation of viral permissiveness and antiviral responses in adaptive immune models. Full article

The identification of novel natural sources of bioactive peptides with multifunctional health-promoting properties remains a major challenge for the development of nutraceutical and therapeutic agents. Prosopis laevigata (mesquite), a plant of economic, medicinal, and nutritional relevance in Mexico, has been poorly explored as a source of protein-derived bioactive molecules. Therefore, this study evaluated the antioxidant, antimicrobial, cytotoxic, and enzymatic inhibitory activities of peptides obtained from the enzymatic hydrolysis of P. laevigata cotyledon proteins. The resulting hydrolysates exhibited significant antioxidant activity, for peptide fractions smaller and larger than 5 kDa, in the ABTS and FRAP assays. Cytotoxic activity against HepG2 liver cancer cells was observed at high peptide concentrations (8 mg/mL). Additionally, the peptides inhibited the growth of Staphylococcus aureus but showed no activity against Escherichia coli. The peptides also displayed partial inhibition of α-amylase activity, with peptides <5 kDa exhibiting competitive inhibition and peptides >5 kDa showing a mixed inhibition pattern. Overall, these findings highlight P. laevigata seeds as a promising source of multifunctional bioactive peptides with potential applications in functional foods and health-related biotechnological developments. Full article

The rapid global spread of antimicrobial resistance among pathogenic microorganisms poses a serious challenge to both human and animal health, underscoring the urgent need for new strategies to combat resistance. Antimicrobial peptides (AMPs), key components of the innate immune system, are promising candidates because they disrupt the membranes of bacteria, fungi, and viruses, thereby reducing the risk of resistance development. Lactoferrin (LF), a multifunctional iron-binding glycoprotein abundant in mammalian milk, is a rich source of AMPs. Cationic peptide fragments such as lactoferricin and lactoferrampin exhibit more potent direct antimicrobial activity than the intact protein. Our previous studies have shown that peptides derived from Equine milk lactoferrin exhibit antihypertensive, anti-inflammatory, and anti-oncogenic activity in silico, highlighting their multifunctional bioactive potential. Building on these results, the present study aims to investigate the antimicrobial properties of these peptides. We used an integrated approach combining computer modeling and in vitro studies to identify and validate novel antimicrobial peptides from equine milk lactoferrin. Bioinformatics tools, including AMPScanner and CAMP, were used to predict antimicrobial domains, followed by experimental testing against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The results showed that equine milk lactoferrin peptides possess potent and selective antimicrobial activity, with efficacy varying across bacterial species. These data expand the functional profile of lactoferrin-derived peptides, demonstrating their multifunctionality, and suggest that equine milk lactoferrin represents a promising natural source of antimicrobial agents, supporting alternative strategies to reduce antibiotic use in human and veterinary medicine. Full article

The aim of this study was to investigate the anti-melanogenic effects and underlying mechanisms of PFRMY (Pro-Phe-Arg-Met-Tyr), a pentapeptide derived from tilapia skin (Oreochromis niloticus), using B16F10 murine melanoma cells. Treatment with PFRMY (1.0 mg/mL) significantly reduced intracellular melanin content and tyrosinase (TYR) activity by 39.55 ± 1.51% and 32.46 ± 1.31%, respectively. RT-PCR and Western blotting analyses revealed that PFRMY suppressed melanogenesis through the α-MSH/PKA/CREB signaling pathway. Notably, PFRMY reversed α-MSH-induced upregulation of key downstream factors including PKA, CREB, MITF, and TYR, while showing minimal effects on the protein expression of MC1R or α-MSH. Molecular docking further suggested that PFRMY binds to MC1R with higher affinity than α-MSH, potentially occupying the ligand-binding site and thereby interfering with downstream signaling. Collectively, these findings demonstrate that PFRMY effectively inhibits melanogenesis by competitively antagonizing the α-MSH/MC1R axis, highlighting its potential as a safe and efficacious ingredient for hyperpigmentation treatment and cosmetic applications. Full article

Macroalgal species are widely distributed throughout the world’s oceans and are well recognised for their biotechnological, ecological, and pharmacological potentials, containing a wide range of diverse bioactive compounds. In many coastal habitats worldwide, excessive accumulations of algal biomass (including rapidly growing blooms and drift accumulations resulting from dislodgement from benthic habitats) are commonplace and can pose environmental and economic challenges. In this study, we report occurrences of algal blooms and drift accumulations during 2024 and 2025 involving three major macroalgal clades, Chlorophyta, Phaeophyceae, and Rhodophyta, from two distinct marine regions: the North Atlantic Ocean and the South Pacific Ocean. Species identified included Grateloupia turuturu, Polyides rotundus, Ascophyllum nodosum, Ulva spp., Sargassum spp. and Fucus spp., among others. The indicated species are known for their diverse pharmacological properties, including antimicrobial, antioxidant, and anti-inflammatory effects. Specialised bioinformatic tools were employed to assess the potential of identified macroalgae as a source of antimicrobial peptides (AMPs). For selected macroalgal species, in silico screening of publicly available databases was performed to identify previously reported and characterised AMPs associated with these species. This in silico approach presents a promising strategy for discovering novel antimicrobial agents with potential activity, especially against drug-resistant bacteria. Finally, applying proteomics methodologies for in silico evaluation of the selected algal species advances modern technologies for the sustainable use of natural resources. Full article

Multicomponent reactions with isocyanides (IMCRs) enable the one-step assembly of complex molecules and remain a powerful strategy for accessing bioactive scaffolds. Here, we report the first synthesis of an abietane diterpene isocyanide derived from aminoimide methyl maleopimarate 1, a levopimaric acid-maleic anhydride adduct. This isocyanide was further engaged in Passerini, Ugi, and azido-Ugi reactions to provide a series of α-acyloxy- and α-acylaminocarboxamides, as well as tetrazoles, in high yields under optimized conditions. The structures of all products were confirmed by comprehensive physicochemical analysis. In silico ADME, drug-likeness, target prediction, and toxicity studies (SwissADME, ProTox-III) revealed moderate lipophilicity with favorable membrane permeability and solubility, high gastrointestinal absorption, and selective CYP3A4 inhibition with no significant effects on other CYP450 isoforms. The compounds fulfill major drug-likeness criteria, lacking undesirable reactive fragments, with only acceptable deviations in molecular weight and flexibility typical for MCR-derived products. The modifications broaden the spectrum of predicted biological targets while maintaining low overall toxicity and absence of predicted hepato- or carcinogenicity. These results demonstrate that diterpene isocyanide is a valuable building block for chemical libraries of structurally diverse abietane derivatives with peptide-like termini and highlight its potential as a source of cytotoxic, antiviral, and anti-inflammatory candidates. Full article

Periodontal disease represents a major global health burden, beginning with gingivitis and progressing to periodontitis, which causes connective tissue breakdown, alveolar bone resorption, and eventual tooth loss. Beyond local pathology, periodontitis is a chronic inflammatory condition with systemic associations, including cardiovascular disease, diabetes, and metabolic disorders. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) have emerged as promising candidates for periodontal regeneration. This review aimed to map the current evidence on MSC-derived EVs (MSC-EVs) in periodontal regeneration, focusing on their mechanisms of action, therapeutic potential, and translational challenges. A comprehensive literature search was conducted across a major biomedical database (PubMed) to identify preclinical and clinical studies investigating MSC-EVs in the context of periodontitis. Data were charted on EV cargo composition, biological functions, regenerative outcomes, and reported limitations. Evidence indicates that MSC-EVs encapsulate bioactive molecules—including antimicrobial peptides, proteins, lipids, and microRNAs—that modulate immune responses, suppress pro-inflammatory signaling, and promote angiogenesis and tissue repair. In periodontal models, MSC-EVs attenuate osteoclast activity, enhance fibroblast proliferation, and stimulate extracellular matrix remodeling, supporting regeneration of periodontal ligament and alveolar bone. Exosome-based approaches demonstrate advantages such as reduced immunogenicity, improved safety, and feasibility for storage and standardization. However, most findings remain preclinical, with limited human data available. To bridge the translational gap, well-designed clinical trials are needed to confirm efficacy and safety while addressing regulatory challenges, GMP standards, and outcome measures. Harnessing their regenerative capacity while mitigating side effects may guide precision-targeted therapies, and continued mechanistic studies with standardized production will be key to advancing MSC-EVs into clinical practice. Full article

The growing production volume of the meat industry has increased the need for revalorization of meat by-products to reduce economic and environmental impacts. Enzymatic hydrolysis of protein-rich meat by-products is an effective strategy for producing hydrolyzates with bioactive potential. Combining sequential enzymatic hydrolysis with γ-glutamyl transpeptidase activity can promote the formation of γ-glutamyl peptides associated with koku perception, a sensory attribute that increases taste intensity, continuity, and palatability. This study aimed to develop porcine liver hydrolyzates enriched in koku-related peptides through enzymatic hydrolysis followed by post-treatment with the transpeptidase Protana Uboost. Substrate specificity assays showed that a 0.2 U/mL enzyme concentration maximized γ-glutamyl dipeptide formation. Sequential hydrolysis using Alcalase and Protana Prime followed by Protana Uboost post-treatment generated the highest levels of koku-related peptides. Moreover, post-treatment significantly enhanced antioxidant capacity in the resulting hydrolyzates, supporting their potential as a functional ingredient. Full article