Search Results (79)

Skin aging is influenced by both internal and external factors, resulting in wrinkles, decreased elasticity and irregular pigmentation. Hyaluronic acid (HA), a key component of the extracellular matrix, is essential for skin hydration and structural support. Peptides, short amino acid chains, have gained attention in cosmetics due to their multifunctional biological activities. This study explored the moisturizing and metal-chelating properties of Chrono Control Penta (S-Cannabis Sativa-pentapeptide-1), a novel plant-derived peptide whose sequence is WVSPL. In vitro, it chelated iron ions up to 17.86 ± 2.50% and copper ions up to 47.08 ± 1.49% at 10 mM and 3 mM, respectively. Western blot and Enzyme-Linked Immunosorbent Assay (ELISA) analysis showed that, under H₂O₂-induced stress, Chrono Control Penta increased hyaluronan synthase 2 (HAS2) production by 81.72% in BJ-5ta fibroblasts and enhanced HA secretion by 20.11% compared to simulated aging conditions alone, respectively. Furthermore, experiments carried out with the Franz diffusion cell and human full thickness skin demonstrated the peptide’s ability to penetrate the skin layers and even diffuse laterally with a quantified peptide skin biodistribution accounting for 0.095/0.06 nM/mg in 6 h. Advanced AI-based modeling (AlphaFold2, RosettaFold) and docking analysis revealed stable peptide-peptide transporter 2 (PEPT2) interactions, supporting carrier-mediated skin permeation and linking computational predictions with experimental diffusion data. Hence, this study extends previous evidence on the cosmetic efficacy of Chrono Control Penta by (i) adding mechanistic insights into metal chelation and HAS2/HA modulation, (ii) rigorously quantifying local skin penetration and lateral diffusion with HPLC-MS/MS, and (iii) providing a plausible mechanistic link between skin biodistribution and PEPT2-mediated transport based on deep learning structural models. Full article

Chronic injuries and diseases related to oxidative stress are major global concerns as they impose a great medical burden and lead to serious public health issues. Antioxidant peptides derived from pea protein can serve as potent antioxidants and food additives, contributing to address the challenges posed by oxidative stress. This review will focus on the antioxidant effects of pea peptides demonstrated in various in vitro chemical, cellular, and in vivo antioxidant models. Additionally, this review also summarizes the regulatory role of pea peptides on the Nrf2 (NF-E2-related factor 2)/Kelch-like ECH-associated protein 1 (Keap1) pathway, aiming to elucidate their antioxidant mechanisms. Our review found that pea peptides with smaller molecular weights (<1 kDa) obtained through enzymatic hydrolysis or fermentation and/or those containing amino acids such as Glu, Asp, Gly, Pro, and Leu tend to exhibit higher antioxidant activity. These pea peptides exert their antioxidant effects by scavenging free radicals, chelating pro-oxidative transition metals, reducing hydrogen peroxide, inactivating reactive oxygen species, enhancing the expression of antioxidant enzymes, and reducing the accumulation of lipid peroxides. Our study provides a theoretical foundation for the development of pea resources and the processing of pea-related functional foods. Full article

Oxidative stress, driven by excess reactive oxygen species (ROS), is a key factor in the progression of neurodegenerative diseases like Alzheimer’s disease (AD). In this context, copper dysregulation can also contribute to this imbalance, being responsible for enhanced ROS production, so that copper scavenging has been investigated as a possible therapeutic strategy. This study investigates the behavior of two isostructural ligands, featuring an N₃O donor set, that effectively chelate Cu(II) in aqueous solution. Interestingly, their resulting mono- or dinuclear copper complexes feature a coordination environment suitable to foster antioxidant activity. By transforming copper’s oxidant potential into antioxidant action, these systems may reduce copper-induced oxidative damage. The work examines the pH-dependent metal-binding behavior of the ligands, the catalytic properties of the resulting complexes under physiological conditions, and their ability to inhibit β-amyloid peptide aggregation. Full article

This study aimed to produce antioxidant peptide fractions from Skipjack tuna (Katsuwonus pelamis) head by-products through enzymatic hydrolysis and membrane filtration. Raw materials were sequentially hydrolyzed with Alcalase^® (4 h) and Flavourzyme^® (1 h), reaching a final degree of hydrolysis of 18.5 ± 0.9%. The crude hydrolysate was fractionated using ceramic membranes with molecular weight cut-offs of 8, 3, and 1 kDa. Some peptide fractions presented a relevant proportion of short-chain peptides (>50% w/w) and free amino acids (>10% w/w), as well as a high content of essential amino acids (>64% mol), supporting their value as dietary ingredients for aquafeeds. In vitro antioxidant activities were assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferrous ion chelation assays. Some fractions (e.g., F3R1 with IC₅₀ = 1.04 ± 0.01 mg·mL⁻¹ for metal chelating activity) displayed significantly improved (p < 0.05) antioxidant properties compared to the unfractionated hydrolysate (IC₅₀ = 2.75 ± 0.08 mg·mL⁻¹). This may be linked to their molecular weight profile and hydrophobic amino acid content. These results demonstrate the potential of the proposed approach to obtain bioactive peptide fractions with functional properties for aquafeeds. Zootechnical trials are needed to assess their effects on feed utilization and in vivo mitigation of oxidative stress. Full article

Among the highly toxic heavy metals, cadmium (Cd) is highlighted as a persistent environmental pollutant, posing serious threats to plants and broader ecological systems. Phytochelatins (PCs), which are synthesized by phytochelatin synthase (PCS), are peptides that play a central role in Cd mitigation through metal chelation and vacuolar sequestration upon formation of Cd-PC complexes. PC synthesis interacts with other cellular mechanisms to shape detoxification outcomes, broadening the functional scope of PCs beyond classical stress responses. Plant Cd-related processes have has been extensively investigated within this context. This perspective article presents key highlights of the panorama concerning strategies targeting the PC pathway and PC synthesis to manipulate Cd-exposed plants. It discusses multiple advances on the topic related to genetic manipulation, including the use of mutants and transgenics, which also covers gene overexpression, PCS-deficient and PCS-overexpressing plants, and synthetic PC analogs. A complementary bibliometric analysis reveals emerging trends and reinforces the need for interdisciplinary integration and precision in genetic engineering. Future directions include the design of multigene circuits and grafting-based innovations to optimize Cd sequestration and regulate its accumulation in plant tissues, supporting both phytoremediation efforts and food safety in contaminated agricultural environments. Full article

This research examined antioxidant and anti-obesity effects of Palmaria palmata extracts obtained through acidic or alkaline treatments and subsequent pH adjustments. After two rounds of acidic or alkaline extraction, the extracts were separated from biomass and adjusted to different pH values: for acidic extracts, pH 3 (no adjustment), pH 6, pH 9, and pH 12; for alkaline extracts, pH 12 (no adjustment), pH 9, pH 6, and pH 3. The findings revealed that extraction medium as well as subsequent pH adjustments significantly influenced composition of the extracts in terms of protein content and recovery, amino acids, and phenolic compounds (p < 0.05). Acidic conditions produced extracts with potent radical scavenging, especially at pH 6 (IC₅₀ = 0.30 ± 0.04 mg.mL⁻¹), while alkaline conditions favored metal chelating, with the highest Fe²⁺ chelation at pH 12 (IC₅₀ = 0.65 ± 0.03 mg.mL⁻¹). Moreover, extracts showed inhibitory activities against porcine pancreatic lipase and α-amylase, with the acidic extract at pH 9 showing the best anti-obesity properties (IC₅₀ = 5.38 ± 0.34 mg.mL⁻¹ for lipase and IC₅₀ = 5.79 ± 0.30 mg.mL⁻¹ for α-amylase). However, the highest α-amylase activity was in the alkaline extract at pH 12 (IC₅₀ = 3.05 ± 0.66 mg.mL⁻¹). In conclusion, adjusting the pH of seaweed extracts notably influences their bioactive properties, likely due to changes in the reactivity and interactions of bioactive compounds such as peptides, carbohydrates, and polyphenols. Full article

This comprehensive review explores the biological functions of Perilla frutescens seed proteins and peptides, highlighting their significant potential for health and therapeutic applications. This review delves into the mechanisms through which perilla peptides combat oxidative stress and protect cells from oxidative damage, encompassing free radical scavenging, metal chelating, in vivo antioxidant, and cytoprotective activities. Perilla peptides exhibit robust anti-aging properties by activating the Nrf2 pathway, enhancing cellular antioxidant capacity, and supporting skin health through the promotion of keratinocyte growth, maintenance of collagen integrity, and reduction in senescent cells. Additionally, they demonstrate antidiabetic activity by inhibiting α-amylase and α-glucosidase. The cardioprotective effects of perilla peptides are underscored by ACE-inhibitory activities and combat oxidative stress through enhanced antioxidant defenses. Further, perilla peptides contribute to improved gut health by enhancing beneficial gut flora and reinforcing intestinal barriers. In liver, kidney, and testicular health, they reduce oxidative stress and apoptotic damage while normalizing electrolyte levels and protecting against cyclophosphamide-induced reproductive and endocrine disruptions by restoring hormone synthesis. Promising anticancer potential is also demonstrated by perilla peptides through the inhibition of key cancer cell lines, alongside their anti-inflammatory and immunomodulating activities. Their anti-fatigue effects enhance exercise performance and muscle function, while perilla seed peptide nanoparticles show potential for targeted drug delivery. The diverse applications of perilla peptides support their potential as functional food additives and therapeutic agents. Full article

Based on the established neuroprotective properties of indole-based compounds and their significant potential as multi-targeted therapeutic agents, a series of synthetic indole–phenolic compounds was evaluated as multifunctional neuroprotectors. Each compound demonstrated metal-chelating properties, particularly in sequestering copper ions, with quantitative analysis revealing approximately 40% chelating activity across all the compounds. In cellular models, these hybrid compounds exhibited strong antioxidant and cytoprotective effects, countering reactive oxygen species (ROS) generated by the Aβ(25–35) peptide and its oxidative byproduct, hydrogen peroxide, as demonstrated by quantitative analysis showing on average a 25% increase in cell viability and a reduction in ROS levels to basal states. Further analysis using thioflavin T fluorescence assays, circular dichroism, and computational studies indicated that the synthesized derivatives effectively promoted the self-disaggregation of the Aβ(25–35) fragment. Taken together, these findings suggest a unique profile of neuroprotective actions for indole–phenolic derivatives, combining chelating, antioxidant, and anti-aggregation properties, which position them as promising compounds for the development of multifunctional agents in Alzheimer’s disease therapy. The methods used provide reliable in vitro data, although further in vivo validation and assessment of blood–brain barrier penetration are needed to confirm therapeutic efficacy and safety. Full article

Cytophaga is a genus of Gram-negative bacteria occurring in soil and the gut microbiome. It is closely related to pathogenic Flavobacterium spp. that cause severe diseases in fish. Cytophaga strain L43-1 secretes cytophagalysin (CPL1), a 137 kDa peptidase with reported collagenolytic and gelatinolytic activity. We performed highly-confident structure prediction calculations for CPL1, which identified 11 segments and domains, including a signal peptide for secretion, a prosegment (PS) for latency, a metallopeptidase (MP)-like catalytic domain (CD), and eight immunoglobulin (Ig)-like domains (D3–D10). In addition, two short linkers were found at the D8–D9 and D9–D10 junctions, and the structure would be crosslinked by four disulfide bonds. The CPL1 CD was found closest to ulilysin from Methanosarcina acetivorans, which assigns CPL1 to the lower-pappalysin family within the metzincin clan of MPs. Based on the structure predictions, we aimed to produce constructs spanning the full-length enzyme, as well as PS+CD, PS+CD+D3, and PS+CD+D3+D4. However, we were successful only with the latter three constructs. We could activate recombinant CPL1 by PS removal employing trypsin, and found that both zymogen and mature CPL1 were active in gelatin zymography and against a fluorogenic gelatin variant. This activity was ablated in a mutant, in which the catalytic glutamate described for lower pappalyins and other metzincins was replaced by alanine, and by a broad-spectrum metal chelator. Overall, these results proved that our recombinant CPL1 is a functional active MP, thus supporting the conclusions derived from the structure predictions. Full article

This study focuses on the use of three isostructural N₆O donor ligands, specifically known to form complexes with copper ions, to chelate Cu(II) from aqueous solutions. The corresponding Cu(II) complexes feature a dinuclear copper core mimicking the active site of natural superoxide dismutase (SOD) enzymes while also creating a coordination environment favorable for catalase (CAT) activity, being thus appealing as catalytic antioxidant systems. Given the critical role of copper dysregulation in the pathophysiology of Alzheimer’s disease (AD), these complexes may help mitigate the harmful effects of free Cu(II) ions: the goal is to transform copper’s reactive oxygen species (ROS)-generating properties into beneficial ROS-scavenging action. This study investigates the speciation, chelating efficiency, and metal selectivity of these ligands, as well as the antioxidant activity of the resulting complexes under aqueous and physiologically relevant conditions. Additionally, the ligands, equipped with functional groups for attaching targeting moieties, are conjugated with a small peptide that may act as an anti-aggregating agent of β-amyloid peptides, aiming to develop a multifunctional therapeutic strategy against Alzheimer’s disease. Full article

Background/Objectives: Excessive reactive oxygen species (ROS) can lead to oxidative stress, which has become an urgent problem requiring effective solutions. Due to the drawbacks of chemically synthesized antioxidants, there is a growing interest in natural antioxidants, particularly antioxidant peptides. Methods: By reviewing recent literature on antioxidant peptides, particularly those extracted from various parts of fish, summarize which fish by-products are more conducive to the extraction of antioxidant peptides and elaborate on their characteristics. Results: This article summarizes recent advancements in extracting antioxidant peptides from fish processing by-products, Briefly introduced the purification and identification process of antioxidant peptides, specifically focusing on the extraction of antioxidant peptides from various fish by-products. Additionally, this article comprehensively reviews the relationship between amino acid residues that compose antioxidant peptides and their potential mechanisms of action. It explores the impact of amino acid types, molecular weight, and structure–activity relationships on antioxidant efficacy. Conclusions: Different amino acid residues can contribute to the antioxidant activity of peptides by scavenging free radicals, chelating metal ions, and modulating enzyme activities. The smaller the molecular weight of the antioxidant peptide, the stronger its antioxidant activity. Additionally, the antioxidant activity of peptides is influenced by specific amino acids located at the C-terminus and N-terminus positions. Simultaneously, this review provides a more systematic analysis and a broader perspective based on existing research, concluded that fish viscera are more favorable for the extraction of antioxidant peptides, providing new insights for the practical application of fish by-products. This could increase the utilization of fish viscera and reduce the environmental pollution caused by their waste, offering valuable references for the study and application of antioxidant peptides from fish by-products. Full article

This study employed a diverse approach to extract antioxidant peptides from red seaweed Palmaria palmata, recognized for its comparatively high protein content. Initially, an aqueous extraction of the entire seaweed was performed, followed by enzymatic hydrolysis of the solid residues prepared from the first step. The effects of three different pH levels (3, 6, and 9) during the aqueous extraction were also examined. Results indicated that the solid fraction from the sequential extraction process contained significantly higher levels of proteins and amino acids than other fractions (p < 0.05). Furthermore, the solid fractions (IC₅₀ ranging from 2.29 to 8.15 mg.mL⁻¹) demonstrated significantly greater free radical scavengers than the liquid fractions (IC₅₀ ranging from 9.03 to 10.41 mg.mL⁻¹ or not obtained at the highest concentration tested) at both stages of extraction (p < 0.05). Among the solid fractions, those produced fractions under alkaline conditions were less effective in radical scavenging than the produced fractions under acidic or neutral conditions. The fractions with most effective metal ion chelating activity were the solid fractions from the enzymatic stage, particularly at pH 3 (IC₅₀ = 0.63 ± 0.04 mg.mL⁻¹) and pH 6 (IC₅₀ = 0.89 ± 0.07 mg.mL⁻¹), which were significantly more effective than those from the initial extraction stage (p < 0.05). Despite no significant difference in the total phenolic content between these solid fractions and their corresponding liquid fractions (3.79 ± 0.05 vs. 3.48 ± 0.02 mg.mL⁻¹ at pH 3 and 2.43 ± 0.22 vs. 2.51 ± 0.00 mg.mL⁻¹ at pH 6) (p > 0.05), the observed antioxidant properties may be attributed to bioactive amino acids such as histidine, glutamic acid, aspartic acid, tyrosine, and methionine, either as free amino acids or within proteins and peptides. Full article

The ability of bacteria to recycle exogenous amino acid-based peptides and amino sugars for peptidoglycan biosynthesis was extensively investigated using optical imaging. In particular, fluorescent AeK–NBD was effectively utilized to study the peptidoglycan recycling pathway in Gram-negative bacteria. Based on these promising results, we were inspired to develop the radioactive AeK conjugate [⁶⁸Ga]Ga-DOTA-AeK for the in vivo localization of bacterial infection using PET/CT. An easy-to-implement radiolabeling procedure for DOTA-AeK with [⁶⁸Ga]GaCI₃ followed by solid-phase purification was successfully established to obtain [⁶⁸Ga]Ga-DOTA-AeK with a radiochemical purity of ≥95%. [⁶⁸Ga]Ga-DOTA-AeK showed good stability over time with less protein binding under physiological conditions. The bacterial incorporation of [⁶⁸Ga]Ga-DOTA-AeK and its fluorescent Aek-NBD analog were investigated in live and heat-killed Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Unfortunately, no conclusive in vitro intracellular uptake of [⁶⁸Ga]Ga-DOTA-AeK was observed for E. coli or S. aureus live and heat-killed bacterial strains (p > 0.05). In contrast, AeK-NBD showed significantly higher intracellular incorporation in live bacteria compared to the heat-killed control (p < 0.05). Preliminary biodistribution studies of [⁶⁸Ga]Ga-DOTA-AeK in a dual-model of chronic infection and inflammation revealed limited localization at the infection site with non-specific accumulation in response to inflammatory markers. Finally, our study demonstrates proof that the intracellular incorporation of AeK is necessary for successful bacteria-specific imaging using PET/CT. Therefore, Ga-68 was not a suitable radioisotope for tracing the bacterial uptake of AeK tripeptide, as it required chelation with a bulky metal chelator such as DOTA, which may have limited its active membrane transportation. An alternative for optimization is to explore diverse chemical structures of AeK that would allow for radiolabeling with ¹⁸F or ¹¹C. Full article

Our preliminary study identified dairy cow placenta extract (CPE) as a mixture of peptides with potent antioxidant activity both in vivo and in vitro. However, the specific antioxidant peptides (AOPs) responsible for this activity were not yet identified. In the current study, we employed virtual screening and chromatography techniques to isolate two peptides, ANNGKQWAEVF (CP1) and QPGLPGPAG (CP2), from CPE. These peptides were found to be less stable under extreme conditions such as high temperature, strong acid, strong alkali, and simulated digestive conditions. Nevertheless, under normal physiological conditions, both CP1 and CP2 exhibited significant antioxidant properties, including free-radical scavenging, metal chelating, and the inhibition of lipid peroxidation. They also up-regulated the activities of intracellular antioxidant enzymes in response to hydrogen-peroxide-induced oxidative stress, resulting in reduced MDA levels, a decreased expression of the Keap1 gene and protein, and increased levels of the Nrf2 and HO-1 genes and proteins. Furthermore, CP1 demonstrated superior antioxidant activity compared to CP2. These findings suggest that CP1 and CP2 hold potential for mitigating oxidative stress in vitro and highlight the efficacy of virtual screening as a method for isolating AOPs within CPE. Full article

The heavy metal cadmium poses severe threats to both ecosystems and human health. Utilizing genetic engineering to enhance the microbial capability for efficient cadmium accumulation has emerged as a pivotal research direction. This study constructed a genetically engineered bacterium capable of expressing multivalent phytochelatins with a self-assembly ability and explored its efficacy in cadmium adsorption. Molecular biology techniques were adopted to fuse the recombinant human ferritin (rHF) gene and the synthetic phytochelatin (EC) gene, known for its robust adsorption capacity for heavy metals. The expression vector was constructed. Escherichia coli (E. coli) served as the host cell to express multivalent nanochelator rHF-ECs tailored for high-efficiency heavy metal adsorption. The results reveal the successful soluble expression of the recombinant fusion protein in E. coli cells, forming self-assembled multivalent nanoparticles with a size of about 13 nm, and the target protein rHF-EC20 (monomer) could adsorb approximately 9.2 μmol of Cd²⁺ in vitro. Moreover, this recombinant strain demonstrated cadmium adsorption across a temperature range of 16–45 °C and a pH range of 5–9, with the optimal performance observed at pH 7.0 and 37 °C. Compared with the control strain, the recombinant strain BL21 (FLE), expressing nano-chelating peptides, achieves an adsorption rate of 80% for Cd²⁺ at 60 min, resulting in an approximately 18% increase in the Cd²⁺ enrichment efficiency. The maximum adsorption capability of cadmium reached 12.62 mg per gram of dry cell weight. This work indicated that the synthesis of multivalent chelating peptides in E. coli cells could efficiently enhance the bioaccumulation of the heavy metal cadmium, which renders novel avenues and methodologies for addressing cadmium pollution, offering promising prospects for environmental remediation. Full article