Search Results (268)

Yellowfin tuna (Thunnus albacares) processing by-products are underutilized resources rich in high-quality proteins that can be valorized into bioactive ingredients. In this study, proteins from yellowfin tuna tail bones were hydrolyzed using either an endogenous protease extract recovered from tuna viscera or commercial trypsin. The endogenous extract was characterized and exhibited optimal proteolytic activity at pH 8 and 40 °C. Comparative bioactivity assessment showed that trypsin-derived hydrolysates exhibited significantly higher antioxidant capacity, with ABTS and DPPH values of 11.8 ± 0.04 and 13.3 ± 0.40 mg Trolox/g, respectively, compared with 10.1 ± 0.12 and 7.3 ± 0.21 mg Trolox/g for hydrolysates produced with endogenous enzymes. Trypsin hydrolysates also showed stronger dipeptidyl peptidase-IV (DPP-IV) inhibition (IC₅₀ = 0.83 ± 0.37 mg/mL) than endogenous-enzyme hydrolysates (IC₅₀ = 1.60 ± 0.47 mg/mL). Remarkably, hydrolysates generated with the endogenous enzymatic consortium exhibited exceptionally potent angiotensin-converting enzyme (ACE) inhibitory activity (IC₅₀ = 0.008 ± 0.004 mg/mL), outperforming trypsin hydrolysates (IC₅₀ = 0.01 ± 0.007 mg/mL). Neither hydrolysate showed evidence of acute toxicity in the Artemia salina model at the tested concentrations, supporting their favorable performance in this preliminary toxicity screening assay. Considering that nearly two-thirds of total fish biomass is discarded during processing, this integrated bioprocess demonstrates a sustainable strategy for the simultaneous valorization of skeletal and visceral waste streams. By employing endogenous enzymes as biocatalysts, this approach reduces dependence on commercial proteases, mitigates environmental burdens, and supports the development of a circular marine bioeconomy through the production of highly potent, peptide-rich functional ingredients with promising cardiovascular health applications. Further toxicological evaluation is required to confirm their safety for food and nutraceutical applications. Full article

Although flaviviruses, including DENV, ZIKV and JEV, remain important causes of febrile, congenital, and neurological diseases, treatment options remain largely supportive, with limited availability of virus-specific antiviral therapies. Marine organisms and marine-derived microorganisms produce chemically distinct antiviral materials, including sulfated polysaccharides, terpenoids, alkaloids, peptides, cyclodepsipeptides, and polyketides. However, their activities range from preliminary extract-level inhibition to direct biochemical target validation, making mechanistic comparison difficult. This review critically evaluates marine-derived anti-flaviviral agents using two complementary dimensions, the infection stage implicated by experimental assays and the strength of evidence supporting that assignment. DENV evidence is dominated by sulfated algal macromolecules that interfere with adsorption or internalization, whereas ZIKV studies encompass lipophilic algal metabolites, fungal alkaloids, cyclodepsipeptides, and a few target-oriented candidates. Across the field, most reports remain stage-associated rather than target-validated. Cross-study potency comparisons are constrained by differences in virus strains, cell models, assay formats, and treatment schedules. JEV-specific evidence is particularly sparse. Based on the DENV and ZIKV evidence map, we propose concise priorities for JEV-oriented discovery: early compound-level dereplication, parallel cytotoxicity testing, orthogonal confirmation of productive infection, stage-resolved assays, and biochemical or genetic validation of conserved flaviviral targets. This evidence-based framework can help distinguish promising chemical candidate scaffolds from preliminary antiviral signals and guide mechanism-informed development of marine-derived natural products against flaviviruses. Full article

Marine-derived rare actinomycetes are a chemically prolific yet underexploited source of structurally diverse secondary metabolites. In this review, rare actinomycetes are operationally defined as marine-derived non-Streptomyces actinomycetes that remain comparatively underexplored yet possess demonstrated or predicted capacity for specialized-metabolite biosynthesis. Genome sequencing has revealed that their biosynthetic potential greatly exceeds the range of metabolites recovered under standard cultivation conditions. However, many reported compounds remain only loosely associated with the gene clusters that encode them. This review provides a biosynthesis-centered perspective on marine-derived rare actinomycetes, focusing on secondary metabolites for which biosynthetic gene clusters (BGCs) or pathways have been proposed, experimentally assessed, or functionally validated. It focuses on compounds reported after 2017, along with earlier metabolites whose biosynthetic origins were resolved only later. Representative examples are organized by genus and structural class and weighed according to the level of evidence linking each metabolite to its BGC, ranging from bioinformatic prediction and metabolomic correlation to validation by gene inactivation, heterologous expression, and enzymatic characterization. The surveyed metabolites include polyketides, nonribosomal peptides, polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids, siderophores, angucyclines, anthracyclines, macrolides, diketopiperazine derivatives, and other unusual scaffolds. Collectively, these findings indicate how integrating genome mining, metabolomics, and molecular networking with targeted biosynthetic experiments can accelerate marine natural product discovery and unravel novel enzymatic functions and biosynthetic mechanisms in rare actinomycetes. Full article

Rare actinomycetes have emerged as important yet underexplored reservoirs for the discovery of novel bioactive compounds. Microbispora, a genus of rare actinomycetes, is widely distributed across diverse ecological niches, including terrestrial soils, marine-associated environments, plant-associated ecosystems, and insect-derived environments. To date, 81 secondary metabolites have been reported from this genus, encompassing quinones, chromones and chromanones, macrolides, other polyketides, alkaloids, peptides and diketopiperazines, and miscellaneous structural classes. These metabolites display antimicrobial, anticancer, neuroprotective, antiviral, plant growth-promoting, and enzyme inhibitory activities. Beyond systematically cataloging these compounds, this review provides an integrated analysis of their structure–activity relationships (SAR), biosynthetic origins, and biological significance. In addition, the biosynthetic potential of Microbispora is discussed based on reported genomic studies, highlighting the presence of numerous predicted and poorly characterized biosynthetic gene clusters. This review provides an integrative perspective on Microbispora as an underexplored but promising source of structurally diverse and bioactive natural products for drug discovery. Full article

The growing demand for sustainable protein sources is driving the development of marine by-product utilization. Mussel byssus, which is currently discarded during mussel processing, could be used to produce collagen-derived biomaterials. This study tested the hypothesis that ultrasound-assisted extraction could improve collagen recovery by comparing its efficiency with that of conventional pepsin-assisted extraction. The latter is time-consuming and inefficient. While conventional pepsin-assisted extraction achieved a higher collagen-derived material recovery yield (10.7%) than ultrasound-assisted extraction (5.1%), ultrasound reduced the extraction time from 72 h to just two hours. Fourier transform infrared spectroscopy (FTIR) confirmed that the characteristic amide bands were preserved in the collagen-derived material extracted using both methods. Differential scanning calorimetry (DSC) revealed thermal transitions at 59 °C for pepsin-assisted extracts and 57 °C for ultrasound-assisted extracts, indicating comparable thermal stability. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed predominantly low-molecular-weight protein fragments (<20 kDa), suggesting the presence of collagen-derived peptides rather than intact native collagen. Overall, ultrasound-assisted extraction preserved the structural and thermal characteristics of the extracted material while drastically reducing processing time. This highlights its potential as a rapid, environmentally friendly and sustainable technology for the valorization of mussel byssus within a circular bioeconomy. Full article

Background/Objectives: Atopic dermatitis (AD) is a multifactorial inflammatory skin disorder in which epidermal barrier disruption and dysregulated immune responses drive persistent cutaneous inflammation. Owing to their broad spectrum of biological activities, marine-derived peptides have attracted increasing attention as potential therapeutic agents capable of modulating inflammatory and immune pathways. Methods: In this study, a novel peptide, WPN-15 (NGAIADQQPQRPNIV), was isolated from enzymatic hydrolysates of walleye pollock (Gadus chalcogrammus) tail by-products using an activity-guided purification process consisting of dialysis, fast protein liquid chromatography-gel permeation chromatography (FPLC-GPC), reverse-phase high-performance liquid chromatography (RP-HPLC), and electrospray ionization mass spectrometry (ESI-MS). The anti-inflammatory activity of WPN-15 was first examined in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and subsequently validated in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis model using six-week-old male BALB/c mice. Results: WPN-15 significantly inhibited nitric oxide production in LPS-stimulated macrophages without causing cytotoxic effects. Topical administration of WPN-15 markedly alleviated DNCB-induced AD-like kin lesions, significantly reduced dermatitis severity scores, and decreased serum interleukin (IL)-6 levels. Histological evaluation further demonstrated that WPN-15 attenuated epidermal hyperplasia, dermal thickening, and mast cell infiltration. Furthermore, WPN-15 significantly downregulated the mRNA expression of IL-1β and IL-6 and inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation in skin tissues, indicating that its protective effects are mediated, at least in part, through the suppression of the IL-6/STAT3 signaling pathway. Conclusions: WPN-15 effectively attenuated inflammatory responses and pathological features associated with experimental AD. These findings demonstrate that walleye pollock tail by-products represent a valuable and sustainable source of bioactive peptides and support the potential application of WPN-15 as a marine-derived therapeutic candidate for the management of AD. Full article

Marine-derived collagen peptides exhibit potent intestinal barrier protection; however, their gastrointestinal fate and molecular targets remain unclear, limiting their practical applications. This study investigated the digestive stability and transepithelial transport of GPSGPQGSR, a mucoprotective peptide from Alaska pollock (Gadus chalcogrammus) skin, using simulated gastrointestinal digestion, a Caco-2 cell transport model, and an UPLC-QTOF-MS/MS. The results showed that GPSGPQGSR was a digestion-resistant peptide that reached the intestinal epithelium intact. Although brush border membrane enzymes partially hydrolysed the peptide, 42.16% of intact GPSGPQGSR remained in the luminal compartment after 2 h of incubation. No intact peptide was detected in the basolateral compartment. Molecular docking and 100 ns molecular dynamics simulations identified TLR2 (−14.936 kcal/mol) and PAR2 (−10.154 kcal/mol) as high-affinity extracellular targets of GPSGPQGSR, with stable peptide–receptor interactions and extensive hydrogen bonding networks between the peptide and each receptor (RMSD of 1.8 Å and 2.2 Å, respectively). Pharmacological blockade of TLR2 or PAR2 abolished the protective effects of GPSGPQGSR. These findings demonstrate that GPSGPQGSR acts as a digestion-resistant extracellular signalling peptide that reaches the intestinal epithelium intact and protects barrier function through apical TLR2 and PAR2, providing a mechanistic basis for the rational development of marine collagen peptides for improving intestinal health. Full article

In this study, a novel composite hydrogel was developed based on oxidized sodium alginate (OSA), synthesized via sodium periodate oxidation, and incorporated into a carboxymethyl chitosan (CMCS) matrix. Scallop active peptides (SAPs), a marine-derived bioactive component with outstanding antioxidant and pro-regenerative activities, was introduced to endow the hydrogel with enhanced biological functions, which is of great significance for breaking the functional limitations of traditional single-component hydrogels. The construction of a dynamic covalent network, driven by the Schiff base reaction, was confirmed through structural characterization using FT-IR and ¹H-NMR. The hydrogel exhibited favorable physicochemical properties, including shear-thinning behavior, significant self-healing capability, and a uniform porous microstructure that effectively mimics the extracellular matrix (ECM). In vitro evaluations revealed excellent biocompatibility and potent pro-angiogenic potential, as evidenced by enhanced HUVEC migration and tube formation. In a rat model of full-thickness skin wounds, the CMCS/OSA/SAPs hydrogel significantly accelerated wound closure and promoted re-epithelialization and organized collagen deposition. Furthermore, immunohistochemical analysis confirmed upregulated VEGF and α-SMA expression, alongside reduced inflammatory levels (decreased iNOS), indicating potent tissue-regenerative and immunomodulatory functions. Overall, this work presents a multifunctional hydrogel system that integrates antioxidant, anti-inflammatory, and tissue-regenerative properties, offering a promising strategy for deep-wound healing. This study highlights the significant potential of marine-derived bioactive proteins/peptides in the development of advanced biomedical materials. Full article

Inflammation plays a critical role in host defense and tissue repair; however, excessive or dysregulated inflammatory responses can lead to tissue damage and contribute to the progression of various diseases. Jellyfish-derived peptides have recently emerged as promising marine bioactive compounds with potential anti-inflammatory activity. In this study, three candidate anti-inflammatory peptides were identified from the enzymatic hydrolysate of Nemopilema nomurai through an integrated strategy combining LC–MS/MS-based peptidomics and multi-step in silico screening. The selected peptides (DGIPGMPG, PGFHVPPP, and GPKGYPGP) were prioritized based on predicted bioactivity, non-toxicity, favorable physicochemical properties, and molecular docking with the TLR4/MD-2/LPS complex (PDB ID: 3FXI), with docking scores ranging from −8.4 to −8.3 kcal/mol. Subsequent experimental validation demonstrated that all three peptides exhibited good cytocompatibility and significantly inhibited LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, with GPKGYPGP showing the strongest effect. In addition, these peptides effectively reduced the secretion of pro-inflammatory cytokines, including TNF-α and IL-1β, to varying extents. Collectively, this study identifies three novel anti-inflammatory peptides derived from jellyfish enzymatic hydrolysates and highlights their potential as promising candidates for the development of marine-derived bioactive agents targeting inflammation-related diseases. Full article

Marine by-products represent a promising source of bioactive peptides. This study aimed to isolate and characterize a low-molecular-weight peptide fraction with antioxidant activity from Argentine shortfin squid carcass by-products, and to evaluate in vitro its cytocompatibility and protective effects against corticosterone (CORT)-induced oxidative injury in rat adrenal pheochromocytoma (PC12) cells and human astrocyte (hACs) cells. Argentine squid antioxidant peptide (PASN) was obtained by size-exclusion chromatography and fractionation-based screening. PASN exhibited the strongest overall free-radical-scavenging activity and consisted predominantly of components below 1 kDa (211.73–1013.48 Da). Spectroscopic analyses indicated that enzymatic hydrolysis transformed its structure from a rigid triple-helix conformation to a more flexible conformation dominated by β-turns (50.78%) and random coils (17.38%). In addition, thermogravimetric analysis confirmed its excellent thermal stability, with an onset decomposition temperature as high as 244.81 °C, supporting its potential applicability in high-temperature food-processing matrices. In vitro assays demonstrated that PASN exhibited high biocompatibility and promoted proliferation of both PC12 cells and hACs, while significantly improving cell viability under CORT challenge. PASN also reduced lactate dehydrogenase (LDH) leakage (hACs: 38.31%; PC12: 31.17%) in both cell models and restored total superoxide dismutase (T-SOD) activity (hACs: 69.46%, PC12: 66.40%). Immunofluorescence further revealed that PASN rescued the expression of brain-derived neurotrophic factor (BDNF) (hACs: 35.23%, PC12: 12.50%) and glutamate decarboxylase (GAD1/2) (hACs: 102.66%, PC12: 31.31%), key markers associated with synaptic plasticity and GABAergic sleep regulation. Collectively, PASN is a thermally stable squid-derived peptide fraction that exerts antioxidant and cytoprotective effects in neural cell models in vitro and represents a promising sustainable candidate for nutraceutical development. Full article

Background/Objectives: Whether habitual dietary omega-3 fatty acid intake is reflected in circulating biomarkers of atrial fibrillation (AF)-related pathways is unclear. We assessed whether usual dietary intake of n-3 fatty acids—considered as total, marine-derived, or non-marine-derived—was associated with the trajectories of five serum markers that reflect AF-related mechanistic pathways [N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), high-sensitivity troponin T (hs-TnT), high-sensitivity C-reactive protein (CRP), the C-terminal propeptide of type-I procollagen (PICP), and 3-nitrotyrosine (3-NT)] over 5 years of follow-up. Methods: In 510 participants of the PREDIMED-Plus trial (older Spanish adults with metabolic syndrome), we measured plasma NT-pro-BNP, hs-TnT, CRP, PICP, and 3-NT at baseline and after 3 and 5 years. Energy-adjusted omega-3 intake was assessed with a validated 143-item food-frequency questionnaire. Cross-sectional and 5-year longitudinal associations according to tertiles of omega-3 fatty acid intake were estimated with linear regression and mixed-effects models. Results: Median total omega-3 intake was 2.0 g/day. Total omega-3 intake was not associated with any biomarker, neither cross-sectionally nor longitudinally. Marine omega-3 was directly associated cross-sectionally with 3-NT (highest vs. lowest tertile +28.4%, 95% CI 5.5 to 56.2; p-trend = 0.014) but not longitudinally. Moderate baseline non-marine omega-3 fatty acid intake was associated with a decrease in PICP after 5 years of follow-up. Conclusions: Overall, habitual total omega-3 fatty acid intake was not associated with circulating AF-related pathways. The sporadic association between marine omega-3 fatty acid intake and 3-NT in the cross-sectional assessment and the isolated non-linear association between baseline non-marine omega-3 fatty acid intake and PICP after 5 years warrant further investigation. Full article

Peptide therapeutics have emerged as a versatile class of biomolecules bridging the gap between small-molecule drugs and large biologics. Advantages of such molecules include high target specificity, potent bioactivity and reduced off-target toxicity. Despite these, broader clinical translation remains constrained by inherent limitations like poor metabolic stability, rapid renal clearance, limited membrane permeability and scalable synthesis. This review aims to systematically integrate advances in peptide science across natural discovery, synthetic methodologies, structural engineering, and translational delivery systems, while identifying critical research gaps hindering clinical adoption. We highlight diverse natural sources of bioactive peptides, including plant- (lunasin), animal- (Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP)), microbial- (nisin and cyclosporine), marine- (dolastatins) and venom-derived (chlorotoxin and ω-conotoxin MVIIA (ziconotide)) agents. Advances in solid-phase peptide synthesis (SPPS), green chemistry, and catalytic strategies are discussed alongside emerging in silico approaches, including artificial intelligence-driven sequence design and molecular modeling. Structural modifications such as cyclization, hydrocarbon stapling, PEGylation, and lipidation are critically evaluated for their role in enhancing pharmacokinetic and pharmacodynamic properties. Furthermore, nanoformulation strategies, including self-assembling peptides and cell-penetrating systems, are examined for their potential to overcome biological barriers. Importantly, this review identifies key unresolved challenges, including the lack of predictive models for peptide delivery systems, safety concerns associated with long-term modifications, and limited in vivo validation of naturally derived peptides. Addressing these gaps through integrated computational and experimental approaches will be essential for advancing next-generation peptide therapeutics. Collectively, this work provides a comprehensive framework for the rational design and translation of peptide-based precision medicines. Full article

The hybrid approach remains a compelling strategy for designing molecules that combine enhanced biological activity with a favorable safety profile. Marine peptides, in particular, have attracted significant attention due to their well-documented broad spectrum of biological activities. Peptides derived from rays have been recognized for their diverse biological activities. Notably, physicochemical properties of these peptides support practical application without requiring further refinement of the mature molecule or specialized formulations. In this study, we present two new chimeric peptides, PK01# and PK02#, which incorporate an opioid pharmacophore linked to a short amino acid sequence derived from the skate Raja porosa. Those compounds interact with the opioidergic system, specifically targeting the mu-opioid receptor (MOR). Furthermore, the compounds were evaluated for their effects on cancer cell viability through in vitro MTT assays (as an exploratory endpoint) and for their binding compatibility with EGFR via in silico docking. Both compounds showed limited effects on cell viability in HeLa, SAS, and PANC-1 cells, while PK02# induced a minor reduction in metabolic activity in glioblastoma cells without reaching IC50 values or significant cytotoxic thresholds. Interestingly, the structures of these hybrid compounds offer valuable insights into the role of phenylalanine residues within their sequences, which appear to be critical for both biological activity and receptor interaction. Moreover, these findings may support future structural optimization of peptide hybrids focused on receptor modulation and biological profiling. Full article

Marine macroalgae, microalgae, and associated microorganisms are increasingly recognised as valuable sources of bioactive compounds with applications across biotechnology and health. The environmental and ecological conditions they inhabit shape their metabolite diversity, leading to the production of high-value compounds such as sulphated polysaccharides, lipids, pigments, phenolics, and peptides. These compounds exhibit conserved biological activities that underpin potent antioxidant, anti-inflammatory, cytotoxic, and pro-regenerative effects with strong potential for translation. Although external factors drive rich metabolite diversity, continual variation can also lead to translational constraints including heavy-metal accumulation, inconsistency in extract composition, and regulatory complexity. This review examines the environmental drivers of metabolite diversity and the functional potential of bioactives derived from marine algae. We focus on their translational application within four areas of growing interest: nutraceuticals, cosmetics, regenerative medicine, and oncology, where emerging evidence suggests their promise as next-generation bioactive ingredients and therapeutic leads. In addition, insights from Irish and Welsh Small and Medium Enterprises (SMEs) are collated to identify key bottlenecks in commercialisation and the requirements for effective marine biodiscovery pipelines. We consider the importance of controlled cultivation, standardised analytics, preclinical testing platforms, and collaborative innovation ecosystems and highlight the need for coordinated scientific, technical, and regulatory advances to unlock the full translational potential of marine-derived compounds. Full article

At present, there is still a lack of effective treatments to slow the progression of Parkinson’s disease. Naturally derived active substances, valued for their safety and multi-target potential, have become an important direction in anti-PD drug development, with marine organisms representing a valuable source of bioactive peptides. This study aimed to isolate and identify anti-PD peptides from Rapana venosa protein hydrolysates. Through bioactivity-guided screening combined with an MPTP-induced zebrafish PD model, three novel active peptides—KSTELLI, FLVKLPMFM, and SDSLSEILIS—were successfully identified. The study showed that these peptides significantly alleviated dopaminergic neuron loss, improved the cerebral vascular system, restored motor and sensory function, and alleviated oxidative stress. Molecular docking confirmed their stable binding to key PD targets (DDC, α-synuclein, and MAO-B). Further transcriptomic and gene expression analyses revealed that their neuroprotective effects involve the regulation of pathways related to metabolism, oxidative stress, inflammation, and apoptosis, with the three peptides exhibiting distinct mechanistic emphases. The research demonstrates that these marine-derived peptides exert neuroprotective effects through a synergistic multi-target mechanism, laying a foundation for the development of novel lead compounds against Parkinson’s disease. Full article