Search Results (7,464)

Background/Objectives: The cerebral cortex is critical for neurological functions that are strongly affected by the aging process. Astrocytes play a central role in maintaining neurotransmitter balance and regulating antioxidant and anti-inflammatory responses, but these physiological functions may also decline with age. This study aimed to investigate the effects of melatonin, a molecule with known antioxidant, anti-inflammatory and neuroprotective properties, on astrocytes of mature cortical tissue obtained from adult Wistar rats. Methods: Primary cortical astrocyte cultures were obtained from neonatal and 90-day-old Wistar rats and treated with melatonin (300 µM for 24 h). We assessed cell viability and metabolism (MTT and extracellular lactate levels), glutamine synthetase (GS) activity, glutathione (GSH) content, release of cytokines, and the expression of genes and proteins associated with oxidative stress and inflammation by RT-qPCR and Western blotting. Results: Melatonin did not affect cell viability or lactate production. Moreover, there were no changes in GS activity, a key enzyme in glutamate metabolism, or in GSH levels, an antioxidant defense molecule synthesized by astrocytes. However, melatonin significantly reduced the expression of the nuclear factor NFκB, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS), while increasing interleukin 6 and 10 levels. Melatonin also upregulated the gene expression of the transcriptional factors Nrf2 and sirtuin 1 (SIRT1) and downregulated AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), while PGC-1α protein levels remained unchanged. A complementary analysis of astrocytes obtained from neonatal rats showed that melatonin did not change metabolic or redox parameters under basal conditions. Conclusions: Melatonin exerted anti-inflammatory effects on adult astrocyte cultures, likely through modulation of protective signaling pathways, such as Nrf2/SIRT1. These findings highlight the potential role of melatonin in preserving astrocytic function and mitigating age-related neuroinflammatory processes. Full article

Background: Amiodarone is a widely used class III antiarrhythmic agent, but its use can lead to peripheral neuropathy mediated by mitochondrial dysfunction, oxidative stress, and neuroinflammatory injury, while effective preventive options remain limited. Agents that support mitochondrial energy metabolism, sustain redox balance, and modulate inflammation, including adenosine triphosphate (ATP), melatonin, and thiamine pyrophosphate (TPP), may counteract these mechanisms; however, their relative neuroprotective potential in amiodarone-induced neuropathy remains unclear. This study aimed to comparatively evaluate the effects of ATP, melatonin, and TPP on amiodarone-induced peripheral neuropathy and neuropathic pain in rats. Methods: Thirty male albino Wistar rats were assigned to five groups: healthy; amiodarone (50 mg/kg/orally); amiodarone + ATP (5 mg/kg/intraperitoneally); amiodarone + melatonin (10 mg/kg/orally); or amiodarone + TPP (20 mg/kg/intraperitoneally). Treatments were given once daily for 14 days. Oxidative stress indices (malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT)) and proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1 Beta (IL-1β), interleukin-6 (IL-6)) were quantified in sciatic nerve by Enzyme-Linked Immunosorbent Assay (ELISA). Paw withdrawal thresholds were measured with the Randall-Selitto test before and after treatment. Histopathology was performed using Hematoxylin-eosin staining. Results: Amiodarone exposure resulted in pronounced elevations in MDA and proinflammatory cytokine levels, accompanied by significant reductions in tGSH, SOD, CAT activities, and paw withdrawal thresholds. ATP, melatonin and TPP ameliorated these alterations to varying degrees. Among them, TPP provided the most robust antioxidant and anti-inflammatory effects, followed by ATP and melatonin. Histopathological examination confirmed most severe axonal degeneration, interstitial edema and Schwann cell proliferation in the amiodarone group, with substantial amelioration in the TPP-treated rats. Conclusions: Amiodarone induces neuropathic pain through oxidative and inflammatory injury to peripheral nerves. TPP exhibited superior neuroprotective efficacy compared with ATP and melatonin, highlighting its potential as a candidate therapeutic agent for amiodarone-related neuropathy. Further clinical research is warranted to support translational application of these findings. Full article

Procyanidin B1 (PB1), a polyphenol abundant in Cyperus esculentus stems and leaves extract (CELE), exhibits antioxidant and anti-inflammatory activities, though its mechanisms are not fully understood. This study investigated CELE’s effects in chickens and LPS-stimulated HD11 macrophages. Chickens fed CELE showed increased blood levels of SOD, GSH-Px, TNF-α, IL-1β, IL-6, and IL-10, while MDA decreased. RNA-seq of LPS + PB1 vs. LPS-treated cells identified 696 differentially expressed genes enriched in inflammation and antioxidant pathways. Analysis indicated 120 transcription factors (TFs) may regulate these changes, with FOSL1, HIF1A, and STAT2 significantly downregulated. In HD11 cells, PB1 reduced expression of HIF1A/STAT2-target genes (e.g., HMGA2, EPSTI1), lowered IL-1β, IL-6, and ROS, and shifted macrophage polarization from M1 to M2. PB1’s effects were enhanced by an HIF1A inhibitor but reversed by a STAT2 activator. These findings support PB1 and CELE as potential feed additives for livestock. Full article

In vitro and in vivo evidence demonstrates that EGT exerts neuroprotective effects through multiple mechanisms: scavenging reactive oxygen species, suppressing neuroinflammatory cytokines (TNF-α, IL-1β, IL-6), activating Nrf2 antioxidant pathways, and preserving mitochondrial integrity. Low blood EGT levels correlate with cognitive decline and dementia, supporting its role as a conditionally essential micronutrient for healthy aging. Mushroom by-products retain EGT concentrations comparable to commercial fruiting bodies, making them viable sources for dietary supplements and functional foods. Mushroom processing generates substantial residual biomass—including stems, culls, and spent substrate—that represents an underexploited dietary source of ergothioneine (EGT), a naturally occurring antioxidant with exceptional neuroprotective and anti-inflammatory properties. Since humans cannot synthesize EGT endogenously, dietary intake is essential for maintaining neuroprotection against neurodegenerative diseases. This review examines sustainable extraction strategies—including hot-water, ultrasound-assisted, and high-hydrostatic-pressure methods—enabling integration into circular biorefinery systems. Applications in nutraceuticals and pharmaceuticals targeting oxidative stress-related neurodegeneration are highlighted. Despite challenges in standardization and regulatory approval, valorizing mushroom residuals offers a sustainable pathway to increase dietary availability of this neuroprotective antioxidant, supporting both environmental sustainability and therapeutic innovation for neurodegenerative disease prevention. Full article

In recent decades, the quantity of sperm and the quality of semen have decreased, causing an increased incidence of male infertility. The increased exposure to environmental pollutants and metals, including aluminum, is one of the causes. Aluminum is reported to activate the proinflammatory macrophages and the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome pathway in many organs. Thymoquinone (TQ), the bioactive component of Nigella sativa, possesses immunomodulatory, anti-inflammatory, anti-apoptotic, and antioxidant properties. The purpose of this work is to investigate how thymoquinone affects aluminum chloride (AlCl₃)-induced testicular damage and to study, for the first time, its role in modifying the inflammasome pathway, specifically NLRP3/caspase-1/IL-1β, and in targeting macrophage polarization. Negative control, TQ control (10 mg/kg/d), AlCl₃ group (100 mg/kg/d), and AlCl₃ + TQ group were the rat groups. Serum testosterone, FSH, and LH were measured, along with a seminal analysis, evaluation of testicular oxidative stress markers, and assessment of testicular enzymes LDH, SDH, and ACP. NLRP3, caspase-1, IL-1β, CD68, and CD163 immunohistochemical staining, as well as histological alterations, were evaluated. TQ could lower oxidative stress markers, limit the AlCl₃-induced activation of the NLRP3/caspase-1/IL-1β inflammasome pathway, and induce macrophage polarization toward an M2 anti-inflammatory phenotype, thereby restoring testicular enzymes, histological structure, semen quality, and hormone levels. Thymoquinone attenuates aluminum chloride-induced testicular injury by inhibiting NLRP3/caspase-1/IL-1β inflammasome signaling and polarizing the macrophages toward an anti-inflammatory M2 phenotype. Full article

Cellulite, or edematous-fibro-sclerotic panniculopathy (EFSP), is a multifactorial condition affecting most postpubertal women, characterized by surface irregularities with significant psychosocial impact. Its pathogenesis involves adipocyte metabolism, fibrous septa, microvascular dysfunction, extracellular matrix (ECM) remodeling, oxidative stress, and low-grade inflammation. Topical therapies remain among the most accessible approaches, acting on specific biological pathways. Osmotic and vSSasomodulatory formulations reduce edema and improve microcirculation, while methylxanthines such as caffeine and aminophylline promote lipolysis and enhance cutaneous blood flow. Retinoids mainly target the ECM, stimulating neocollagenesis and dermal thickening, with greater efficacy in early EFSP. Botanicals, including Centella asiatica, Rosmarinus officinalis, and Ginkgo biloba, provide antioxidant, anti-inflammatory, and venotonic effects. Randomized controlled trials consistently report modest but reproducible benefits: localized circumference reductions and improved elasticity, echogenicity, and orange-peel scores, all with excellent tolerability. Recent innovations, such as lipid nanoparticles, ultradeformable vesicles, and microneedle-assisted delivery, aim to enhance penetration, stability, and sustained bioactivity of established actives. Nonetheless, most studies are small, short-term, and heterogeneous, with limited ability to isolate the role of individual components or control for massage-related effects. Artificial intelligence offers opportunities to standardize outcome measures, optimize formulations, and personalize protocols. Overall, topical therapies are best positioned as safe, biologically active adjuncts within multimodal cellulite management. Full article

Glucosinolate-derived metabolites play central roles in plant defense and are increasingly recognized for their pharmacological importance. Barbarea vulgaris produces a structurally diverse set of such compounds, yet their biological activities remain insufficiently explored. In this study, natural metabolites and their synthetic analogues were evaluated for antimicrobial, antibiofilm, antioxidant, and anti-inflammatory properties. Antimicrobial activity was assessed against human and plant pathogens by determining minimum inhibitory and minimum microbicidal concentrations, antibiofilm potential was examined using microplate assays, and radical scavenging activity was measured by DPPH and ABTS assays. In addition, the compounds were screened for inhibitory effects on lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). Phenolic derivatives, particularly methyl-4-hydroxyphenylethyl dithiocarbamate (2) and 2-(4-hydroxyphenyl)ethyl isothiocyanate (8), exhibited notable in vitro antibacterial activity (MIC 0.312–1.25 mg mL⁻¹ against E. coli ATCC 25922 and S. aureus ATCC 25923) and detectable antibiofilm effects. Racemic barbarin (4) preferentially inhibited LOX, underscoring its potential as an anti-inflammatory scaffold, whereas COX-2 inhibition was weak across all tested compounds. None of the metabolites showed radical scavenging activity, suggesting that their effects rely on enzyme inhibition or microbial interactions rather than nonspecific antioxidant mechanisms. This study provides an integrated evaluation of B. vulgaris metabolites, highlighting their ecological role in plant defense and their potential as scaffolds for novel antimicrobial and anti-inflammatory agents. Full article

Crescentia alata is valued in traditional medicine for its anti-inflammatory and antimicrobial properties. However, research on its phytochemical composition and bioactivity is scarce. Phenolic compounds are of pharmacological interest because they reduce oxidative stress and inflammation. This study aimed to optimize the pressurized liquid extraction of phenolic compounds to enhance the cellular antioxidant activity of the fruit extract. Response Surface Methodology with a Box–Behnken Design was used. Three variables were evaluated at three levels: temperature (25, 37.5, and 50 °C), pressure (10, 30, and 50 bar), and time (10, 20, and 30 min). The effect of these variables was monitored on the total phenolic content, total flavonoid content, and the percentage of inhibition of reactive oxygen species. The optimal extraction conditions were 40.98 °C, 29.52 bar, and 16.89 min, which yielded a TPC of 28.27 mg GAE/g DW, TFC of 19.08 mg QE/g DW, and 72.05% ROS inhibition. This methodology proved to be effective for optimizing the extraction of phenolic compounds and revealed the influence of extraction conditions on their biological activity. Full article

The actinobacterial strain Kitasatospora griseola JNUCC 62 was isolated from volcanic wetland soil at Mulyeongari Oreum, Jeju Island, and taxonomically identified through 16S rRNA gene and whole-genome analyses. The complete genome, assembled from PacBio Sequel I reads, spans 8.31 Mb with a GC content of 72.8% and contains 7265 coding sequences. Comparative genomic indices (Average nucleotide identity, ANI 97.46%; digital DNA–DNA hybridization, dDDH 84.4%) confirmed its conspecific relationship with K. griseola JCM 3339^T. Genome mining using antiSMASH 8.0 revealed 30 biosynthetic gene clusters (BGCs), including polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), ribosomally synthesized and post-translationally modified peptide (RiPP), lanthipeptide, and terpene types, accounting for 18.6% of the genome. Several BGCs displayed homology to known formicamycin-, lankacidin-, and lanthipeptide-type clusters, while others were novel or cryptic, reflecting adaptation to the nutrient-poor volcanic environment. Ethyl acetate extraction of the culture broth, especially under tryptophan-supplemented conditions, yielded four metabolites—1-acetyl-β-carboline, perlolyrine, tryptopol, and 1H-pyrrole-2-carboxylic acid—identified by UV and NMR spectroscopy. These compounds correspond to NRPS–PKS hybrid and arylpolyene-type gene clusters predicted in the genome, suggesting precursor-directed biosynthesis of indole and pyrrole alkaloids. The ethyl acetate extract (JNUCC62 EA) exhibited strong antioxidant capacity in the ABTS assay, anti-inflammatory activity via inhibition of nitric oxide (31.09 ± 3.69% of control) and cytokines (IL-6, IL-1β, TNF-α) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and anti-melanogenic effects in α-melanocyte-stimulating hormone (MSH)-stimulated B16F10 melanoma cells, where melanin content and tyrosinase activity decreased to 61.49 ± 1.24% and 24.32 ± 0.31% of the control, respectively, without cytotoxicity. A human primary skin irritation test confirmed no irritation up to 50 µg/mL, establishing excellent dermal safety. Collectively, these findings highlight K. griseola JNUCC 62 from Mulyeongari Oreum as a volcanic wetland-derived actinomycete harboring rich biosynthetic potential for novel indole alkaloids with antioxidant, anti-inflammatory, and whitening properties, supporting its development as a safe and multifunctional cosmeceutical ingredient. Full article

Globularia alypum L. (Plantaginaceae) is widespread in the Mediterranean region and traditionally used against diabetes, digestive disorders, infections, and skin problems. This review summarizes its botanical features, ethnobotanical uses, phytochemistry, pharmacological effects, and toxicological profile. Relevant studies published between 1991 and 2024 were retrieved from Web of Science, Scopus, PubMed, and other relevant databases using targeted keywords in English and French. Extracts of G. alypum have shown significant antidiabetic, antioxidant, anticancer, antibacterial, anti-inflammatory, anticoagulant, nephroprotective, and wound-healing activities in vitro and in vivo, which were largely attributed to its diverse secondary metabolites such as phenolics, flavonoids, and iridoids. Toxicological studies indicate generally low risk at tested doses. However, further research is needed to elucidate the molecular mechanisms underlying these activities, validate its efficacy through clinical trials, and evaluate long-term safety, thereby bridging traditional knowledge with modern pharmacological evidence. Full article

Heart failure (HF) is increasing in prevalence in many countries around the world. HF is a complex clinical syndrome characterized by the heart’s inability to pump blood effectively, resulting in significant morbidity and mortality. After an initial cardiac event (e.g., myocardial infarction, valve dysfunction, hypertension, etc.), adaptive mechanisms are activated to preserve cardiac function. Sustained activation of these mechanisms leads to cellular and structural changes involving cardiac remodeling and hypertrophy. This ultimately leads to impaired cardiac contractility and reduced cardiac output, with a 5-year HF-associated mortality rate up to 75%. The current treatment strategies for HF are not sufficient to cover all the underlying complex mechanisms. It has been demonstrated that molecular hydrogen (H₂) exerts cardioprotective effects via its antioxidant, anti-inflammatory, and anti-apoptotic action. The number of studies exploring beneficial effects of H₂ in different HF models is increasing. This is the first review summarizing the knowledge in this field. The available literature indicates that H₂ may be effective in mitigating different HF pathologies via regulating cardiac oxidative stress and inflammation, cardiomyocyte death, and mitochondrial function/cell metabolism, as well as cardiac remodeling, including hypertrophy and fibrosis. As this area of research is still in its infancy, the feasibility and efficiency of H₂ treatment in different HF types need further investigation. Full article

Diabetic wounds represent a significant clinical challenge due to a complex pathological microenvironment marked by hyperglycemia, persistent inflammation, and high susceptibility to infection. Metal composite hydrogels have emerged as a next-generation therapeutic platform that uniquely combines the multifaceted capabilities of metal components, such as potent antibacterial, anti-inflammatory, and antioxidant activities, with the ideal moist healing properties of hydrogels. This review focuses on recent progress in the design strategies for these materials, including physical, chemical, and hybrid doping methods. The review then details their multimodal mechanisms of action, including direct antibacterial pathways, like reactive oxygen species generation and photothermal therapy, along with immunomodulatory interventions that regulate macrophage polarization and resolve chronic inflammation. Furthermore, their role in promoting tissue repair processes, such as angiogenesis and collagen remodeling, is discussed. Finally, the review critically examines prevailing challenges and future directions concerning biosafety, scalable fabrication, and clinical translation, with the goal of providing a comprehensive reference for advancing novel therapies for diabetic wound care. Full article

Valonea, a natural product from Quercus variabilis, is rich in bioactive phenolic compounds; however, its compact physical structure restricts the efficient extraction of these components, limiting its high-value applications. To address this issue, the present study examined the influence of steam explosion (SE) pretreatment on the physical structure, phenolic profile, and bioactivity of valonea and identified optimal processing parameters. Under optimal conditions (1.0 MPa and 10 min), the content of total polyphenols increased by 63.1%, reaching 553.0 mg/g extract, while gallic acid and ellagic acid concentrations increased by 380.6% and 1280.0%, respectively. Electrospray ionization mass spectrometry identified 12 major phenolic constituents, providing a compositional basis for the observed bioactivities. The extract exhibited strong antioxidant and anti-inflammatory properties, confirming that SE not only augments phenolic content but also preserves or enhances the functional quality of the extract. As an efficient and environmentally friendly pretreatment technology, SE substantially improves the bioavailability and activity of phenolics in valonea. Thus, this study offers a reliable strategy for the high-value utilization of valonea in fields such as pharmaceuticals, functional foods, and animal feed. Full article

Background: Cardiovascular diseases, driven by platelet hyperactivation and thrombosis, remain the leading global cause of death. Excessive platelet activation contributes to atherosclerosis and thrombo-inflammatory disorders, underscoring the urgent need for safer and more effective antiplatelet agents. Objectives:Xanthium strumarium L. (X. strumarium) has been reported to exhibit a wide range of pharmacological effects, including anti-inflammatory and antioxidant activities. However, its antiplatelet and antithrombotic effects remain unexplored. Therefore, the present study aimed to comprehensively evaluate the antiplatelet and antithrombotic effects of X. strumarium through integrated in vitro and in vivo experiments. Methods: The principal bioactive compounds present in the X. strumarium extract were identified through GC–MS analysis. In vitro antiplatelet effects were evaluated via light transmission aggregometry, scanning electron microscopy (SEM), ATP and calcium mobilization assays, αIIbβ3 binding assay, clot retraction assay, and Western blotting. In vivo ferric chloride-induced (FeCl₃) murine thrombus model was established to evaluate thrombogenesis. Results: Our results demonstrated that X. strumarium at 25, 50, or 100 μg/mL significantly inhibited collagen, ADP, U46619, and thrombin-induced platelet aggregation. SEM revealed that X. strumarium pretreatment markedly preserved the resting platelet morphology and inhibited collagen-induced activation and shape changes. Further, the granule secretion, integrin-αIIbβ3 signaling, and the MAPK and PI3K/Akt pathways were also concentration-dependently inhibited. The in vivo blood flow rate and mice survival were improved, and H&E staining further revealed a concentration-dependent prevention of arterial occlusion following X. strumarium treatment. Conclusions: Collectively, X. strumarium demonstrated potent antiplatelet and antithrombotic effects, improving blood flow and survival while preventing arterial occlusion. Full article

Chronic inflammation is implicated in the development of various multifactorial diseases, including cancer, diabetes, arthritis, cardiovascular disorders, Alzheimer’s disease, and autoimmune diseases. The enzymes that play a key role in the onset of the inflammation are cyclooxygenases (COXs) and lipoxygenases (LOXs). In recent years, cinnamic acid hybrid molecules, particularly those incorporating a nitric oxide (NO) donor moiety, have attracted considerable attention as potential pharmacological agents for the treatment of multifactorial diseases. In the present study, novel cinnamic acid–nitric oxide (NO) donor hybrids were synthesized as multitarget agents and evaluated for their antioxidant, anti-inflammatory, and cytotoxic properties. In particular, hybrids 5a–i, 6a–i, 9a–i, and 11 were synthesized and evaluated as lipid peroxidation and LOX inhibitors, while selected molecules were further tested as COX-1 and COX-2 inhibitors. Hybrids 6a–i, 9a–i, and 11 that contain a NO donor moiety, were additionally tested as albumin denaturation inhibitors and for their ability to release NO. The results indicated that compound 9a is a promising multitarget agent, exhibiting the lowest IC₅₀ for LOX inhibition, significant antioxidant activity, and the highest NO donor potency. Furthermore, compound 9e demonstrated significant inhibitory activity against both COX-2 and LOX, suggesting its potential as a dual COX–LOX inhibitor. Additionally, compound 6i exhibited the strongest cytotoxic activity among the tested compounds, with EC₅₀ values ranging from 36 to 45 μM across multiple cancer cell lines. All synthesized compounds were also evaluated through in silico studies. Full article