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28 pages, 1046 KB  
Review
Nanoformulated Curcumin for Food Preservation: A Natural Antimicrobial in Active and Smart Packaging Systems
by Edith Dube
Appl. Biosci. 2025, 4(4), 46; https://doi.org/10.3390/applbiosci4040046 (registering DOI) - 13 Oct 2025
Abstract
Food spoilage and contamination remain pressing global challenges, undermining food security and safety while driving economic losses. Conventional preservation strategies, including thermal treatments, refrigeration, and synthetic additives, often compromise nutritional quality and raise sustainability concerns, thereby necessitating natural, effective alternatives. Curcumin, a polyphenolic [...] Read more.
Food spoilage and contamination remain pressing global challenges, undermining food security and safety while driving economic losses. Conventional preservation strategies, including thermal treatments, refrigeration, and synthetic additives, often compromise nutritional quality and raise sustainability concerns, thereby necessitating natural, effective alternatives. Curcumin, a polyphenolic compound derived from Curcuma longa, has demonstrated broad-spectrum antimicrobial, antioxidant, and anti-inflammatory activities, making it a promising candidate for food preservation. However, its poor solubility, instability, and low bioavailability limit direct applications in food systems. Advances in nanotechnology have enabled the development of nanoformulated curcumin, enhancing solubility, stability, controlled release, and functional efficacy. This review examines the antimicrobial mechanisms of curcumin and its nanoformulations, including membrane disruption, oxidative stress via reactive oxygen species, quorum sensing inhibition, and biofilm suppression. Applications in active and smart packaging are highlighted, where curcumin nanoformulation not only extends shelf life but also enables freshness monitoring through pH-responsive color changes. Evidence across meats, seafood, fruits, dairy, and beverages shows improved microbial safety, oxidative stability, and sensory quality. Multifunctional systems, such as hybrid composites and stimuli-responsive carriers, represent next-generation tools for sustainable packaging. However, challenges remain with scale-up, migration safety, cytotoxicity, and potential promotion of antimicrobial resistance gene (ARG) transfer. Future research should focus on safety validation, advanced nanocarriers, ARG-aware strategies, and regulatory frameworks. Overall, nanoformulated curcumin offers a natural, versatile, and eco-friendly approach to food preservation that aligns with clean-label consumer demand. Full article
21 pages, 3935 KB  
Article
Polyporusterone B Alleviates Inflammatory Injury via Suppression of Pro-Inflammatory Cytokine Production
by Dan Song, Yanru Zhang, Jialu Yuan, Xiaohua Hao, Shizhuo Chen, Xinjie Zhao and Yaomeng Yang
Int. J. Mol. Sci. 2025, 26(20), 9957; https://doi.org/10.3390/ijms26209957 (registering DOI) - 13 Oct 2025
Abstract
Polyporusterone B, a triterpene carboxylic acid isolated from Polyporus umbellatus Fries, exhibits anti-cancer and anti-hemolytic activities; however, its anti-inflammatory properties and underlying mechanisms remain unelucidated. We studied the anti-inflammatory effects of Polyporusterone B using lipopolysaccharide (LPS)-stimulated Raw264.7 murine macrophages (in vitro) and LPS-induced [...] Read more.
Polyporusterone B, a triterpene carboxylic acid isolated from Polyporus umbellatus Fries, exhibits anti-cancer and anti-hemolytic activities; however, its anti-inflammatory properties and underlying mechanisms remain unelucidated. We studied the anti-inflammatory effects of Polyporusterone B using lipopolysaccharide (LPS)-stimulated Raw264.7 murine macrophages (in vitro) and LPS-induced endotoxin shock in C57BL/6 mice (in vivo). Results showed that Polyporusterone B (1, 5, and 10 μM) had no cytotoxicity toward Raw264.7 cells, but significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6)) in a concentration- and time-dependent manner, as demonstrated by Griess assay, qPCR, and ELISA. Western blot analysis revealed that Polyporusterone B suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (ERK, P38, and NK) and reduced phosphorylation-mediated degradation of inhibitor of κBα (IκBα). Immunofluorescence and immunohistochemical staining further confirmed that Polyporusterone B blocked nuclear translocation of nuclear factor kappa-B (NF-κB)/Rel A in both Raw264.7 cells and mouse tissues. In the in vivo model, Polyporusterone B pretreatment significantly mitigated LPS-induced multi-organ pathological damage (e.g., lung edema, hepatic inflammation, renal hemorrhage) and downregulated tissue levels of TNF-α, IL-1β, and IL-6. These findings suggest that Polyporusterone B exerts anti-inflammatory effects by inhibiting the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, suggesting its potential as a therapeutic candidate for inflammatory diseases. Full article
(This article belongs to the Special Issue Cytokines in Inflammation and Health)
30 pages, 24475 KB  
Article
Integration of Network Pharmacology, Molecular Docking, and In Vitro Nitric Oxide Inhibition Assay to Explore the Mechanism of Action of Thai Traditional Polyherbal Remedy, Mo-Ha-Rak, in the Treatment of Prolonged Fever
by Chinnaphat Chaloemram, Ruchilak Rattarom, Anake Kijjoa and Somsak Nualkaew
Pharmaceuticals 2025, 18(10), 1541; https://doi.org/10.3390/ph18101541 (registering DOI) - 13 Oct 2025
Abstract
Background: Prolonged fever (PF) is one of the most challenging clinical conditions due to its complex molecular mechanisms and limited effective treatments. Objective: The current study aimed to explore the mechanism of action of Mo-Ha-Rak (MHR), a Thai traditional polyherbal remedy, in PF [...] Read more.
Background: Prolonged fever (PF) is one of the most challenging clinical conditions due to its complex molecular mechanisms and limited effective treatments. Objective: The current study aimed to explore the mechanism of action of Mo-Ha-Rak (MHR), a Thai traditional polyherbal remedy, in PF treatment. Methods: Integration of network pharmacology, molecular docking, and inhibition of nitric oxide (NO) production in LPS-induced RAW264.7 macrophages approaches were used. Results: The study identified 86 potential active compounds, 131 potential therapeutic targets, and 9 hub genes for MHR. Key targets with the highest degree of connectivity in PF, including TNF, IL6, IL1B, PTGS2, STAT3, and NFKB1, are closely associated with arachidonic acid metabolism pathways, which play critical roles in infections, inflammation, cell proliferation, and apoptosis in the PF microenvironment. Molecular docking analysis suggested that core compounds exhibited strong binding affinities for four key targets, viz. TNF, IL6, IL1B, and PTGS2, with binding energies ranging from −4.1 to −9.8 kJ/mol. MHR exhibited dose-dependent reduction of NO production at concentrations of 10–100 µg/mL. Among the biomarkers of MHR tested, ellagic acid, loureirin A, resveratrol, and rhein showed potential to inhibit NO production. Conclusions: This study demonstrates that MHR exerts its therapeutic effects on PF through a complex network of multiple compounds, targets, and pathways. These findings highlight the mechanisms of PF and the role of MHR in modulating the arachidonic acid metabolism pathway, which underlies the development of fever. Full article
(This article belongs to the Section Natural Products)
16 pages, 8320 KB  
Article
Bactericidal and Anti-Inflammatory Effects of Ashitaba-Extract Ameliorate the Gingivitis and Halitosis in Dogs with Porphyromonas gulae-Infected Periodontal Disease
by Takayoshi Miyamoto, So Shirahata, Mariko Komuro, Mao Kaneki, Chiharu Ohira and Tomoki Fukuyama
Vet. Sci. 2025, 12(10), 981; https://doi.org/10.3390/vetsci12100981 (registering DOI) - 13 Oct 2025
Abstract
Ashitaba (Angelica keiskei) is a perennial herb native to Japan, traditionally consumed as a health-promoting food and herbal medicine. This study evaluated the antimicrobial, anti-halitosis, and anti-inflammatory effects of Ashitaba extract on canine periodontal disease (PD) caused by Porphyromonas gulae ( [...] Read more.
Ashitaba (Angelica keiskei) is a perennial herb native to Japan, traditionally consumed as a health-promoting food and herbal medicine. This study evaluated the antimicrobial, anti-halitosis, and anti-inflammatory effects of Ashitaba extract on canine periodontal disease (PD) caused by Porphyromonas gulae (P. gulae). In vitro, Ashitaba extract (0.006–0.1%) significantly inhibited P. gulae viability by up to 80% and reduced biofilm formation by approximately 10% at 0.1%. The extract also suppressed the production of volatile sulfur compounds—hydrogen sulfide and methyl mercaptan—by over 80% and 40%, respectively, within 10 min. Furthermore, Ashitaba extract markedly decreased P. gulae-induced pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α) by up to 90% in murine, canine, and human macrophage and gingival cell lines. In vivo, daily oral application of 0.05% Ashitaba-extract gel for four weeks, with or without tooth brushing, significantly improved gingivitis scores (by 40–60%), reduced halitosis levels, and decreased P. gulae DNA detection and enzymatic activity in dogs with PD. These findings demonstrate that Ashitaba extract possesses potent bactericidal, anti-halitosis, and anti-inflammatory properties, supporting its potential as a natural adjunctive therapy for the prevention and management of canine periodontal disease. Full article
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
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18 pages, 3817 KB  
Article
Melatonin Protects Intact Rat Ovarian Transplantation via the MT1/Nrf2/ARE Pathway
by Lingyun Xie, Shanshan Wang, Yuling Wu, Xuyin Zhang and Yan Ding
Cells 2025, 14(20), 1588; https://doi.org/10.3390/cells14201588 (registering DOI) - 13 Oct 2025
Abstract
Cryopreservation and transplantation of intact ovaries offer a promising approach to fertility restoration in cancer patients. However, ischemia–reperfusion injury following transplantation significantly impairs graft function. This study aimed to evaluate the protective effects of melatonin and elucidate its underlying mechanisms of action, including [...] Read more.
Cryopreservation and transplantation of intact ovaries offer a promising approach to fertility restoration in cancer patients. However, ischemia–reperfusion injury following transplantation significantly impairs graft function. This study aimed to evaluate the protective effects of melatonin and elucidate its underlying mechanisms of action, including antioxidant and anti-inflammatory properties. Intact ovaries from 8 to 12-week-old LEWIS rats were cryopreserved and subsequently transplanted. Melatonin (25 mg/kg and 50 mg/kg) was administered daily from day 1 to day 4 postoperatively. Estrous cycle recovery and ovarian histology were examined, along with measurements of hormone concentrations, antioxidant activity, and inflammatory mediators. The oxidative stress response, particularly the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathway—including Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and sMafg—was investigated to elucidate melatonin’s protective mechanisms. The roles of melatonin receptors and Nrf2 were investigated using specific receptor antagonists (Luzindole, 4P-PDOT) and an inhibitor (ML385) to confirm the involvement of the MT1/Nrf2/ARE pathway. As a result, rats treated with high-dose melatonin (50 mg/kg) exhibited accelerated estrous cycle recovery, reduced follicular loss, improved serum hormone levels, enhanced antioxidant capacity in serum and ovarian tissue, and decreased levels of inflammatory cytokines. Furthermore, melatonin exerted its antioxidant and anti-inflammatory effects through activation of the Nrf2/ARE signaling pathway via the MT1 receptor. These protective effects were abolished by the inhibition of either Nrf2 or MT1 receptor. In conclusion, these findings demonstrate that melatonin mitigates oxidative stress and inflammatory damage in intact transplanted ovaries through the MT1/Nrf2/ARE signaling axis, thereby preserving ovarian function post-transplantation. Full article
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26 pages, 2367 KB  
Review
Exploring Cannabidiol’s Role in Regenerative Medicine: Focus on Neural and Skeletal Tissues
by Rogerio Leone Buchaim, Livia Cristina Dias, Fabiana Gomes Cardoso Pereira de Sousa, Samuel de Sousa Morais, Alexandre José Jacintho, Marina Ribeiro Paulini, João Paulo Mardegan Issa and Daniela Vieira Buchaim
Biomedicines 2025, 13(10), 2490; https://doi.org/10.3390/biomedicines13102490 (registering DOI) - 13 Oct 2025
Abstract
Cannabidiol (CBD) is a non-psychotropic compound found in plants of the Cannabis genus, extensively studied for its therapeutic potential. Research has shown that CBD possesses anti-inflammatory, antioxidant, and regenerative properties, and may contribute to the recovery of neural and bone tissues. In light [...] Read more.
Cannabidiol (CBD) is a non-psychotropic compound found in plants of the Cannabis genus, extensively studied for its therapeutic potential. Research has shown that CBD possesses anti-inflammatory, antioxidant, and regenerative properties, and may contribute to the recovery of neural and bone tissues. In light of the aging population and the resulting rise in neurodegenerative and osteodegenerative conditions, exploring novel therapeutic strategies that promote cellular regeneration is increasingly important. This review aims to compile and critically analyze key studies published in recent decades regarding the effects of CBD on the regeneration of the central and peripheral nervous systems, as well as bone tissue. Findings from in vivo studies indicate that CBD can attenuate inflammatory responses, inhibit oxidative stress, and modulate cellular pathways involved in tissue repair, thereby supporting neuronal and bone regeneration. Moreover, evidence suggests that CBD may protect cells from structural damage, enhancing the functional recovery of affected tissues. Despite scientific advances highlighting cannabidiol as a promising agent for bone and nerve regeneration, its therapeutic application still faces significant limitations. The primary challenge lies in the lack of robust clinical trials in humans, as most existing evidence is derived from in vitro and in vivo studies, making it difficult to confirm its efficacy and safety in clinical contexts. Additionally, CBD’s low bioavailability—due to first-pass hepatic metabolism—hinders dose standardization and reduces the predictability of therapeutic outcomes. Compounding these issues are regulatory constraints and the persistent social stigma surrounding cannabis-derived compounds, which further impede their integration and acceptance in regenerative medicine. Therefore, future research is essential to validate the therapeutic benefits of CBD and to establish its clinical applicability in treating neurological and bone disorders. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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22 pages, 2520 KB  
Review
Marine Bioactive Peptides in the Regulation of Inflammatory Responses: Current Trends and Future Directions
by D. M. N. M. Gunasekara, H. D. T. U. Wijerathne, Lei Wang, Hyun-Soo Kim and K. K. A. Sanjeewa
Proteomes 2025, 13(4), 53; https://doi.org/10.3390/proteomes13040053 (registering DOI) - 13 Oct 2025
Abstract
Marine-derived bioactive peptides (MBPs) are emerging as promising natural agents for regulating inflammatory responses. MBPs, typically obtained through enzymatic hydrolysis of proteins from various marine organisms such as fish, mollusks, and algae, exhibit diverse biological activities, including antioxidant, immunomodulatory, and anti-inflammatory effects. The [...] Read more.
Marine-derived bioactive peptides (MBPs) are emerging as promising natural agents for regulating inflammatory responses. MBPs, typically obtained through enzymatic hydrolysis of proteins from various marine organisms such as fish, mollusks, and algae, exhibit diverse biological activities, including antioxidant, immunomodulatory, and anti-inflammatory effects. The ability of MBPs to modulate key inflammatory mediators such as TNF-α, IL-6, and COX-2, primarily through pathways like NF-κB and MAPK, highlights the therapeutic potential of MBPs in managing chronic inflammatory diseases. However, most existing studies are confined to in vitro assays or animal models, with limited translation to human clinical applications. This review explores the stability, bioavailability, and metabolic rate of MBPs under physiological conditions, which remain poorly understood. In addition, a lack of standardized protocols for peptide extraction, purification, and efficacy evaluation hinders comparative analysis across studies and also different proteomics approaches for separation, purification, identification, and quantification of marine-derived peptides with therapeutic properties. The structure–function relationship of MBPs is also underexplored, limiting rational design and targeted applications in functional foods or therapeutic products. These limitations are largely due to a lack of consolidated information and integrated research efforts. To address these challenges, this review summarizes recent progress in identifying MBPs with anti-inflammatory potentials, outlines key mechanisms, and highlights current limitations. Additionally, this review also emphasizes the need to enhance mechanistic understanding, optimize delivery strategies, and advance clinical validation to fully realize the therapeutic potential of MBPs. Full article
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17 pages, 4365 KB  
Article
Boldo Restores Vascularization and Reduces Skeletal Muscle Inflammation in Symptomatic Mice with Dysferlinopathy
by Walter Vásquez, Felipe Troncoso, Andrea Lira, Carlos Escudero and Juan C. Sáez
Int. J. Mol. Sci. 2025, 26(20), 9945; https://doi.org/10.3390/ijms26209945 (registering DOI) - 13 Oct 2025
Abstract
Dysferlinopathies are progressive muscular dystrophies caused by DYSF mutations, leading to impaired membrane repair, chronic inflammation, lipid accumulation, and muscle degeneration. No approved therapies currently halt the progression of this disease. Here, we evaluated the effects of daily oral administration of pulverized Boldo [...] Read more.
Dysferlinopathies are progressive muscular dystrophies caused by DYSF mutations, leading to impaired membrane repair, chronic inflammation, lipid accumulation, and muscle degeneration. No approved therapies currently halt the progression of this disease. Here, we evaluated the effects of daily oral administration of pulverized Boldo (Peumus boldus) leaves, commonly used as a nutraceutical, to blAJ mice, a model of dysferlinopathy. Symptomatic bIAJ mice were treated for four weeks with Boldo and presented significantly improved grip strength and restored endothelial-dependent vasodilation. Muscle perfusion and capillary density in the gastrocnemius were both enhanced by treatment. Histological analyses revealed that Boldo prevented myofiber atrophy, reduced centrally nucleated fibers, and improved muscle tissue architecture. Lipid accumulation observed in blAJ muscles was absent in Boldo-treated mice. At the cellular level, Boldo normalized sarcolemma membrane permeability (dye uptake) and reduced mRNA levels of inflammasome components (NLRP3, ASC, and IL-1β), suggesting anti-inflammatory activity. These findings indicate that Boldo improves vascular and muscle integrity, supporting its potential as a complementary therapeutic strategy for dysferlinopathy. Full article
(This article belongs to the Special Issue Plant Natural Products for Human Health and Disease)
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22 pages, 2776 KB  
Article
The Effect of Cucumaria frondosa Tentacles Hydrolysates on Dextran Sulfate Sodium-Induced Colitis: Integrated Metagenomics and Metabolomics Analysis
by Senyu Zhang, Qiuting Wang, Shunmin Gong, Mingbo Li, Yu Zhang, Leilei Sun and Liqin Sun
Foods 2025, 14(20), 3483; https://doi.org/10.3390/foods14203483 (registering DOI) - 13 Oct 2025
Abstract
Inflammatory bowel disease continues to pose substantial therapeutic challenges in modern gastroenterology. This study systematically evaluated the anti-colitis efficacy of Cucumaria frondosa tentacles hydrolysates (CFTHs) using a dextran sulfate sodium (DSS)-induced murine colitis model. Characterized by enhanced stability and solubility with molecular weights [...] Read more.
Inflammatory bowel disease continues to pose substantial therapeutic challenges in modern gastroenterology. This study systematically evaluated the anti-colitis efficacy of Cucumaria frondosa tentacles hydrolysates (CFTHs) using a dextran sulfate sodium (DSS)-induced murine colitis model. Characterized by enhanced stability and solubility with molecular weights below 1000 Da, administration of CFTHs demonstrated a significant mitigation in colitis pathology. Therapeutic outcomes included an improved splenic index, attenuated colonic mucosal damage, and substantial decreases in serum pro-inflammatory cytokines. Relative to the DSS group, the MPO value in the CFTHs-H group decreased by 27.6%, and the IL-6 value exhibited a reduction of 33%. Metagenomic profiling revealed that CFTHs mediated gut microbiota modulation, particularly the enrichment of beneficial Bacteroidetes and suppression of pro-inflammatory Proteobacteria. Metabolomic analysis identified elevated colonic concentrations of anti-inflammatory metabolites such as gamma-linolenic acid and prostaglandin I2, suggesting a microbiome–metabolome crosstalk in the therapeutic mechanism. These multi-omics findings in a murine model suggest that CFTHs may represent a promising candidate for future studies as a nutraceutical intervention for inflammatory bowel disorder. This intervention may operate through mechanisms that include simultaneous immunomodulation, microbiota restoration, and metabolic reprogramming. Full article
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17 pages, 800 KB  
Review
Sirtuin Family in Acute Kidney Injury: Insights into Cellular Mechanisms and Potential Targets for Treatment
by Songyuan Yang, Wu Chen, Siqi Li, Sheng Zhao and Fan Cheng
Biomolecules 2025, 15(10), 1445; https://doi.org/10.3390/biom15101445 - 13 Oct 2025
Abstract
Acute kidney injury (AKI) is a frequent clinical and pathological condition, often resulting from factors like ischemia, toxins, or infections, which cause a sudden and severe decline in renal function. This, in turn, significantly affects patients’ overall health and quality of life. The [...] Read more.
Acute kidney injury (AKI) is a frequent clinical and pathological condition, often resulting from factors like ischemia, toxins, or infections, which cause a sudden and severe decline in renal function. This, in turn, significantly affects patients’ overall health and quality of life. The Sirtuin family (SIRTs), a group of Nicotinamide Adenine Dinucleotide (NAD+)-dependent deacetylases, is critically involved in key biological processes such as cellular metabolism, stress responses, aging, and DNA repair. Recent research has highlighted the vital role of SIRTs, such as SIRT1, SIRT3, and SIRT6, in the development and progression of AKI. These proteins help mitigate renal injury and facilitate kidney repair through mechanisms like antioxidant activity, anti-inflammatory responses, cellular repair, and energy metabolism. Additionally, the deacetylase activity of the SIRTs confers protection against AKI by modulating mitochondrial function, decreasing oxidative stress, and regulating autophagy. Although the precise mechanisms underlying the role of Sirtuins in AKI are still being explored, their potential as therapeutic targets is increasingly being recognized. This paper will discuss the mechanisms by which the SIRTs influence AKI and examine their potential in a future therapeutic strategy. Full article
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24 pages, 14107 KB  
Article
Optimization of EPA-Nattokinase Nanoemulsions Processed by High-Pressure Homogenization to Enhance Stability and Thrombolytic Efficacy
by Jiaxing Wang, Shanshan Xu, Liang Chen, Pingan Zheng, Ru Song, Yan Song, Jipeng Sun and Bin Zhang
Foods 2025, 14(20), 3482; https://doi.org/10.3390/foods14203482 (registering DOI) - 12 Oct 2025
Abstract
This study leverages nanoemulsion technology to engineer a novel liquid formulation combining Eicosapentaenoic acid (EPA) and Nattokinase (NK), aiming to enhance their application potential in functional foods. Both EPA and NK are well recognized for their pronounced anti-thrombotic, anti-inflammatory, and lipid-lowering properties, which [...] Read more.
This study leverages nanoemulsion technology to engineer a novel liquid formulation combining Eicosapentaenoic acid (EPA) and Nattokinase (NK), aiming to enhance their application potential in functional foods. Both EPA and NK are well recognized for their pronounced anti-thrombotic, anti-inflammatory, and lipid-lowering properties, which are critical for the prevention and management of cardiovascular diseases. However, their practical application in functional foods is hampered by inadequate gastrointestinal stability and suboptimal bioavailability. Here, an EPA-NK nanoemulsion was fabricated using high-pressure homogenization technology. We systematically evaluated its environmental stability, anti-thrombotic activity, and intervention efficacy against carrageenan-induced black-tail thrombosis. The results demonstrated that the nanoemulsion not only enhanced the potential for oral bioavailability based on in vitro stability and preliminary in vivo efficacy trends of EPA and NK but also notably potentiated their synergistic anti-thrombotic efficacy, thereby providing robust theoretical and technical support for the development of next-generation health-promoting functional foods targeting thrombotic disorders. Full article
(This article belongs to the Section Food Physics and (Bio)Chemistry)
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19 pages, 6476 KB  
Article
Research on the Protective Effects and Mechanisms of Gallic Acid Against Cognitive Impairment Induced by Chronic Sleep Deprivation
by Xiangfei Zhang, Jingwen Cui, Jing Sun, Fengzhong Wang, Bei Fan and Cong Lu
Nutrients 2025, 17(20), 3204; https://doi.org/10.3390/nu17203204 (registering DOI) - 12 Oct 2025
Abstract
Background: Gallic acid (GA) is a dietary polyphenol widely found in walnuts, tea leaves, and grapes, and it is recognized for its potent antioxidant and anti-inflammatory properties. Chronic sleep deprivation (CSD) is known to disrupt redox balance, promote neuroinflammation, and impair cognition, [...] Read more.
Background: Gallic acid (GA) is a dietary polyphenol widely found in walnuts, tea leaves, and grapes, and it is recognized for its potent antioxidant and anti-inflammatory properties. Chronic sleep deprivation (CSD) is known to disrupt redox balance, promote neuroinflammation, and impair cognition, while effective nutritional strategies to mitigate these effects remain scarce. This study was designed to evaluate the protective potential of GA against CSD-induced cognitive deficits in mice and to elucidate the underlying mechanisms. Methods: Seventy-two male ICR mice were randomly allocated to six groups, including control, CSD model, Ginkgo biloba extract, and GA at three doses (50, 100, and 200 mg/kg). After 28 days of treatment, cognitive performance was assessed using the open field test (OFT), novel object recognition (NOR), step-through passive avoidance (ST), and Morris water maze (MWM). Redox status and inflammatory mediators were determined by ELISA, while the hippocampal expression of proteins related to antioxidant defense and NF-κB signaling was analyzed by Western blotting. Results: GA supplementation improved exploratory activity, recognition memory, and spatial learning in the CSD mice. Biochemical evaluation revealed that total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were restored, while malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were reduced. These changes were accompanied by decreased circulating concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). At the molecular level, GA enhanced the expression of Nrf2, HO-1, and NQO1, while inhibiting p-p65, iNOS, and COX2 in the hippocampus. Conclusions: These findings demonstrate that GA alleviates CSD-induced cognitive deficits through the activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB–mediated inflammatory responses. Thus, GA may represent a promising nutraceutical candidate for maintaining cognitive health under chronic sleep loss. Full article
(This article belongs to the Special Issue Therapeutic Potential of Phytochemicals in Neurodegenerative Diseases)
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22 pages, 1813 KB  
Review
Immunoproteasomes in Skeletal Muscle Pathologies: Emerging Roles, Conflicting Evidence, and Future Directions
by Alexander Kalinkovich and Gregory Livshits
Cells 2025, 14(20), 1586; https://doi.org/10.3390/cells14201586 (registering DOI) - 12 Oct 2025
Abstract
Skeletal muscle pathologies, including sarcopenia, inflammatory myopathies, and various muscular dystrophies, are strongly influenced by chronic low-grade inflammation and impaired proteostasis. Immunoproteasomes (IMPs), inducible proteolytic complexes activated by pro-inflammatory cytokines, are emerging as regulators linking immune signaling to protein quality control. Evidence suggests [...] Read more.
Skeletal muscle pathologies, including sarcopenia, inflammatory myopathies, and various muscular dystrophies, are strongly influenced by chronic low-grade inflammation and impaired proteostasis. Immunoproteasomes (IMPs), inducible proteolytic complexes activated by pro-inflammatory cytokines, are emerging as regulators linking immune signaling to protein quality control. Evidence suggests that IMPs have paradoxical, context-dependent roles in skeletal muscle. On one hand, they can support proteostasis and muscle regeneration under stress; on the other, persistent activation may sustain cytokine production, antigen presentation, and maladaptive immune–muscle interactions, promoting chronic inflammation and muscle wasting. Selective IMP inhibitors, such as ONX 0914 and KZR-616, display potent anti-inflammatory effects in preclinical models of autoimmune myositis and muscle atrophy. Yet, their use in skeletal muscle pathologies is controversial; while inhibition may dampen harmful immune activation, it could also impair muscle repair and proteostasis. This review summarizes current findings, highlights key contradictions, and explores unresolved questions about the role of IMPs in skeletal muscle pathologies. We emphasize the need for a deeper understanding of IMP-mediated mechanisms in skeletal muscle pathology and strategies combining selective inhibitors to enhance therapeutic efficacy while minimizing adverse effects. IMPs thus represent both a promising and potentially risky therapeutic target, with outcomes highly dependent on disease context. Full article
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32 pages, 5594 KB  
Article
In Vitro Antioxidant Activity and In Vivo Neuroprotective Effect of Parastrephia quadrangularis in a Drosophila Parkinson’s Disease Model
by Branco Cárdenas, Ayza Cuevas, Duxan Arancibia, Lucas Urrutia, Pedro Zamorano, Adrián Paredes and Rafaella V. Zárate
Antioxidants 2025, 14(10), 1226; https://doi.org/10.3390/antiox14101226 - 12 Oct 2025
Abstract
Oxidative stress (OxS) is a central factor in neurodegenerative diseases (NDs), including Parkinson’s disease (PD). Phenolic compounds, including flavonoids and coumarins, counteract reactive species and modulate key intracellular survival pathways, highlighting their therapeutic potential. Parastrephia quadrangularis (Pq), a plant from the [...] Read more.
Oxidative stress (OxS) is a central factor in neurodegenerative diseases (NDs), including Parkinson’s disease (PD). Phenolic compounds, including flavonoids and coumarins, counteract reactive species and modulate key intracellular survival pathways, highlighting their therapeutic potential. Parastrephia quadrangularis (Pq), a plant from the Atacama Desert traditionally used by Andean communities, contains phenolic compounds with antioxidant, antifungal, and anti-inflammatory activities. However, its neuroprotective potential remains unexplored. Here, a hydroalcoholic extract (HAE) of Pq and four subfractions (MeOH, EtOAc, DCM, and n-hex) were obtained and assessed for in vitro antioxidant activity, with HAE selected for its consistent activity. In SH-SY5Y cells, HAE-Pq lowered basal reactive oxygen species and attenuated hydrogen peroxide-induced OxS. The UHPLC-MS analysis of HAE-Pq unveiled a high abundance of flavonoids, followed by coumarins and phenolic acids, and identified 16 additional metabolites, including jaceidin as the most abundant. In vivo assays using a Drosophila genetic PD model induced by overexpression of human α-synuclein, showed that HAE-Pq was non-toxic and non-aversive and that it delayed the onset of motor defects by one week in female flies. This study provides the first evidence of the neuroprotective potential of Pq, supporting its value as a source of bioactive metabolites relevant to NDs and reinforcing its ethnopharmacological validation. Full article
(This article belongs to the Special Issue Antioxidant Research in Chile—2nd Edition)
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20 pages, 1440 KB  
Article
Phenolic Compounds in Plant-Based Milk Alternatives from the Greek Market
by Velisaria-Eleni Gerogianni, Christiana Mantzourani, Maria A. Theodoropoulou, Antonia Chiou and Maroula G. Kokotou
Separations 2025, 12(10), 282; https://doi.org/10.3390/separations12100282 (registering DOI) - 11 Oct 2025
Abstract
Plant-based milk alternatives (PBMAs) are plant-based fluid products that are marketed as substitutes for regular milk. The nutrient composition of PBMA products can vary widely, depending on the plant source, processing methods, potential additives, etc., and in recent years, considerable research effort has [...] Read more.
Plant-based milk alternatives (PBMAs) are plant-based fluid products that are marketed as substitutes for regular milk. The nutrient composition of PBMA products can vary widely, depending on the plant source, processing methods, potential additives, etc., and in recent years, considerable research effort has been devoted to the exploration of the nutritional content of PBMAs, which are increasingly consumed worldwide. In the present study, an established UHPLC–Orbitrap MS method was employed for the extensive characterization of phenolic compounds in PBMAs available in the Greek market. Twenty-eight PBMAs were studied, including a variety of almond-, soy-, coconut-, oat-, walnut-, and rice-based products. In almond-based milk products, low total concentrations and a broad distribution across compound classes were observed, with trans-chlorogenic acid and neochlorogenic acid being the most abundant constituents, whereas coconut-based milk samples were generally not rich in phenolic compounds. In soy-based milk samples, the presence of isoflavones including daidzein, genistein, and glycitein was uniquely detected, while oat-based products were the samples richer in phenolic content, in particular for hydroxycinnamic acids, such as trans-chlorogenic acid and neochlorogenic acid. In addition, a suspect screening approach, using Exactive Plus Orbitrap, enabled the exploration and semi-quantification of three avenanthramides (A, B, C) in the studied oat-based milk samples and six isoflavonoids, namely daidzein and genistein derivatives, in soy-based milk. Such compounds are known for their antioxidant and anti-inflammatory properties, and their occurrence in PBMAs highlights the potential health-promoting effects of these dairy alternatives. Full article
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