Search Results (2,194)

A novel synthetic approach was developed to synthesize 6-methoxy substituted imidazo[1,2-a]pyridine derivatives, with the objective of obtaining analogs of previously identified antileishmanial hit compounds. The nitration of 8-bromo-2-(chloromethyl)-6-methoxyimidazo[1,2-a]pyridine under classical nitric acid/sulfuric acid conditions resulted in selective nitration at position 5 and the corresponding 3,5-dinitrated derivative. The structures of these compounds were established through a combination of experimental methods, including ¹H and ¹³C NMR, HRMS, HSQC, and HMBC experiments. These structural determinations were subsequently confirmed through single-crystal X-ray diffraction. These compounds represent the first examples of 5-nitrated and 3,5-dinitrated 6-methoxyimidazo[1,2-a]pyridines. Full article

This paper reports new results on the synthesis and comparative characterization of cellulose nitrates (CNs) derived from Miscanthus × giganteus stems and from commercial microcrystalline cellulose (MCC). Miscanthus CNs synthesized by nitration with mixed sulfuric–nitric acids containing 16–20% water exhibit new functional properties: a high solubility in organic solvents (100% in acetone and 97–99% in alcohol–ether solvent) and a high viscosity (17–51 mPa·s), with a nitrogen content of 10.54–12.08 wt%. CNs from Miscanthus × giganteus are similar in nitrogen content and solubility to those from MCC (11.54% and 99%) but have a significantly greater viscosity (3 mPa·s), which is an undoubted advantage and considerably expands their potential application range. The solubility test of CNs synthesized from both sources demonstrated that Miscanthus CNs have a better film-forming ability. SEM analysis revealed a great difference in fiber length, despite the same cylindrical shape and observed aggregation: 1.0–2.0 mm for CNs from Miscanthus versus 40–60 μm for CNs from MCC. IR spectra of CNs from both sources showed the appearance of five new characteristic frequencies (1632–1633, 1273–1274, 823–826, 748, 677–686 cm^–1 for Miscanthus CNs and 1659, 1277, 832, 747, 691 cm^–1 for CNs from MCC), allowing the obtained compounds to be identified as nitric acid esters of cellulose. According to TGA/DTA analysis, the synthesized polymers have similarly high values of the onset temperature of both intense decomposition (197–198 °C) and narrow exothermic peaks (209–211 °C and 212 °C), respectively, indicating their high thermal stability. The combination of high solubility, viscosity, thermal stability and chemical purity of CNs derived from Miscanthus × giganteus stems suggests that strong thin films can be obtained and recommended for use in the manufacture of nitrocellulose membranes. Full article

This study investigates the optimization of extraction conditions, phytochemical contents, biological activities, and cosmeceutical potential of Eurycoma longifolia Jack extracts obtained from wild and cultivated plant roots, stems, and leaves. HPLC analysis revealed that eurycomanone was predominantly accumulated in the root extracts. Among the extraction solvents, 70% ethanol exhibited the most effective extraction of bioactive compounds. Leaf extracts showed the highest total flavonoid content (255.71–269.67 mg quercetin/g sample) and total phenolic content (20.34–20.80 mg gallic acid/g sample). Furthermore, 70% ethanol leaf extracts demonstrated strong antioxidant activity with DPPH IC₅₀ values of 6.37 ± 0.74 and 7.95 ± 0.86 µg/mL for wild and cultivated samples, respectively, and potent tyrosinase inhibitory activity with IC₅₀ values of 50.71 ± 3.92 and 55.80 ± 4.75 µg/mL. The extracts also exhibited selective antibacterial activity against Gram-positive bacteria. Moreover, the in silico molecular docking of biflorin against the 2QVD protein exhibited the highest binding affinity (−7.4 kcal/moL). Anti-inflammatory activity was evidenced by nitric oxide inhibition in LPS-stimulated RAW 264.7 macrophages without significant cytotoxicity. Overall, 70% ethanol extracts, particularly from leaves and roots, exhibited promising biological activities and may serve as potential natural ingredients for future cosmeceutical applications. However, further studies are required to confirm their efficacy and safety before practical applications can be considered. Full article

Oxidative stress and inflammation are central environmental contributors to skin aging, accelerating extracellular matrix (ECM) breakdown and loss of dermal structure. Although Nypa fruticans is recognized for its antioxidant properties, the constituents responsible for these effects remain undefined. To address this, we screened five major polyphenols—protocatechuic acid (PA), hydroxybenzoic acid (HA), procyanidin B1 (PB), catechin (CA), and epicatechin (EC)—for protective activity in two inflammatory skin cell models: human dermal fibroblasts (HDFs) stimulated with tumor necrosis factor-α (TNF-α), and human epidermal keratinocytes (HEKs) co-stimulated with TNF-α and interferon-γ (IFN-γ). PB emerged as the most consistently active compound. In fibroblasts, it suppressed intracellular reactive oxygen species, limited matrix metalloproteinase-1 (MMP-1) release, and restored pro-collagen I α1 output. In keratinocytes, it reduced both pro-inflammatory cytokines—interleukin (IL)-6, IL-8, and IL-1β and inflammatory mediators, including prostaglandin E₂ (PGE₂), cyclooxygenase-2 (COX-2), and nitric oxide (NO). At the transcriptional level, PB shifted the ECM balance by lowering MMP expression while elevating collagen- and hyaluronan-associated genes. Collectively, these results position PB as a principal driver of the protective activity of Nypa fruticans (N. fruticans) leaves under inflammatory conditions. Mechanistically, PB suppressed nuclear factor kappa B (NF-κB) activation and promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation in keratinocytes, supporting its dual anti-inflammatory and antioxidant activities. Full article

Proton pump inhibitors (PPIs) are widely prescribed for acid-related disorders and are generally considered safe for short-term use. However, increasing experimental and clinical evidence suggests potential cardiovascular effects associated with chronic exposure, possibly related to endothelial dysfunction and impaired nitric oxide bioavailability. Therefore, we decided to investigate whether the cardiovascular effects of omeprazole are dependent on the timing of administration in a model of cardiac ischemia–reperfusion (CIR) in normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR). Twelve- to sixteen-week-old male NWR and SHR were allocated into four groups: (1) SHAM: NWR and SHR were submitted to surgery with no ischemia; (2) (SS+CIR): NWR and SHR were treated with a 0.9% saline solution and submitted to CIR; and (3) (OME+ISQ): NWR and SHR were treated with 10 mg/kg i.v. omeprazole (OME) before cardiac ischemia and submitted to CIR or (4) after cardiac ischemia but before cardiac reperfusion (ISQ+OME). Electrocardiograms were monitored to assess ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET). Serum creatine kinase-MB (CK-MB) levels were quantified, and histopathological analyses were performed to evaluate the degree of myocardial injury in the different study groups. Administration of OME prior to cardiac ischemia increased the incidence of VA, AVB, LET, and serum CK-MB levels in both NWR and SHR. In contrast, administration before cardiac reperfusion did not exacerbate cardiac injury and was associated with the attenuation of electrophysiological instability. Histopathological findings corroborated the biochemical and functional outcomes. OME, when administered prior to cardiac ischemia, worsens both cardiac arrhythmias and myocardial injury; however, administration immediately prior to cardiac reperfusion does not increase cardiac arrhythmias and decreases myocardial injury in both NWR and SHR. Full article

Fritillaria species are rich in steroidal alkaloids and are traditionally used for various medicinal purposes. This study investigated the biological activities of methanol, tertiary alkaloid, and quaternary alkaloid extracts obtained from the bulbs of Fritillaria imperialis and Fritillaria pinardii. Methanol, tertiary alkaloid, and quaternary alkaloid extracts prepared from the bulbs of both species were analyzed for secondary metabolites using LC-HRMS. Antimicrobial, cytotoxic, antioxidant, anti-inflammatory, and anticholinesterase activities were evaluated using standard in vitro assays. LC-HRMS analysis identified fumaric acid as the major metabolite in both species, together with (-)-epigallocatechin, cynarin, herniarin and several pyrrolizidine alkaloid N-oxides. Antibacterial activity was restricted to Staphylococcus aureus, whereas alkaloid-rich fractions displayed strong antifungal activity, particularly against Aspergillus fumigatus and Candida spp., with inhibition zones reaching 40 mm. At 80 μg/mL, the most pronounced reductions in cell viability were observed for F. imperialis methanol extract in A549 cells (55.19 ± 2.74%) and for F. pinardii tertiary alkaloid extract and F. imperialis quaternary alkaloid extract in MCF-7 cells (49.68 ± 1.83% and 49.76 ± 1.09%, respectively), whereas all extracts maintained J774 macrophage viability above 94%. Antioxidant activity was most pronounced in the quaternary alkaloid extract of F. pinardii (DPPH IC₅₀ = 90.42 μg/mL; ABTS IC₅₀ = 57.22 μg/mL), although all extracts were less active than the reference antioxidants. The tertiary alkaloid extract of F. pinardii exhibited potent anti-inflammatory activity, showing 5-LOX inhibition comparable to indomethacin (IC₅₀ = 20.05 ± 0.23 μg/mL) and suppressing LPS-induced nitric oxide production by up to 62.22%. Among the tested samples, the tertiary alkaloid extract of F. pinardii exhibited the strongest cholinesterase inhibitory activity against AChE (IC₅₀ = 13.39 ± 0.02 μg/mL). The results indicate that both F. imperialis and F. pinardii extracts exhibit measurable biological activities under in vitro conditions, with the alkaloid-rich extracts of F. pinardii showing comparatively stronger antifungal, anti-inflammatory, and anticholinesterase effects. Full article

This research examined host metabolic processes associated with gingivitis and potential impacts of interventions. First, gingival brush samples from a previously reported clinical study in which participants used an intervention (stannous fluoride (SnF₂) toothpaste/cetylpyridinium chloride rinse/oscillating-rotating electric toothbrush) or control (standard fluoride toothpaste/manual toothbrush) were analyzed with Metabolon metabolomic assessment. Next, hypotheses were generated about mechanisms of metabolic observations and tested in two in vitro models. Human primary blood cells were treated with endotoxins and outer membrane vesicles (OMVs) in the presence of SnF₂. In clinical brush samples, 46 metabolites decreased with intervention at Week 3, including 9- and 13-hydroxyoctadecadienoic acid, citrulline, adenine, and hypoxanthine. Seven metabolites related to nitrogen metabolism and citrulline production were selected for targeted quantification. They were low in health and increased in gingivitis. Targeted quantification demonstrated reduced citrulline, succinate, ornithine and deoxycarnitine (p ≤ 0.001 for all) between baseline and Week 6 with intervention; reductions were greater for intervention vs. control for citrulline, succinate and deoxycarnitine at Week 6 (p ≤ 0.019). In vitro, endotoxin and OMVs increased citrulline and nitric oxide (NO). SnF₂ inhibited elevation of both. Citrulline, deoxycarnitine, succinate, and ornithine were identified as potential novel markers of gingivitis. Elevated NO production is a potential driver of oxidative stress, reduced with intervention. Full article

Marine halophytes are gaining attention as a source of plant-derived bioactive compounds with potential applications across nutraceuticals, functional foods, and preventive nutrition. Among them, Salicornia europaea L. is a coastal succulent whose adaptation to hypersaline environments shapes a distinctive phytochemical profile of pharmacological interest. This narrative review integrates current evidence on the bioactive composition, mechanistic activities, and translational relevance of S. europaea and related Salicornia species. Their secondary metabolome includes flavonols, isorhamnetin glycosides, hydroxycinnamic acids, oleanane-type triterpene saponins, fermentable polysaccharides, carotenoids, and a mineral-rich ionic matrix. Reported activities span antioxidant, anti-inflammatory, vascular-protective, anti-adipogenic, glycaemic-modulating, antimicrobial, and microbiome-related effects, mediated through pathways involving NF-κB, PPAR-γ, endothelial nitric oxide signalling, and short-chain fatty acid production. Beyond its individual phytochemical components, the matrix as a whole may also support sodium-reduction strategies in food formulation, providing a complementary nutritional rationale for its incorporation as a functional ingredient. Despite a coherent body of mechanistic and preclinical findings, clinical evidence remains limited, particularly regarding long-term efficacy, dose standardisation, and bioavailability in humans. Future work should prioritise adequately powered intervention trials and standardised characterisation of marine halophyte bioactives to clarify their evidence-based role in functional food development and future precision nutrition applications. Full article

Background/Objectives: American trypanosomiasis, caused by Trypanosoma cruzi, remains a major public health challenge due to the limited efficacy and adverse effects associated with current treatments. Octyl gallate (OG), a semi-synthetic derivative of gallic acid, has demonstrated promising biological activities, including antiparasitic effects. Methods: The in vitro trypanocidal activity of OG was evaluated against T. cruzi. Mechanism of action studies included the inhibition of the trypanothione reductase enzyme and flow cytometry assays to measure cell death pathways (propidium iodide uptake). Additionally, the immunomodulatory potential of the compound was investigated by assessing cytokine production and innate immune responses. Results: In this study, the trypanocidal activity of OG against different evolutionary forms of T. cruzi was investigated. Using MTT-based viability assays, OG exhibited significant activity against epimastigotes (IC50 = 5.92 ± 0.47 µM), trypomastigotes (EC50 = 3.20 ± 0.14 µM), and intracellular amastigotes (EC50 = 4.07 ± 0.72 µM). The compound also demonstrated favorable selectivity indices, particularly against trypomastigotes and amastigotes, indicating selective toxicity toward the parasite compared to mammalian host cells. In infected macrophages, OG increased TNF-α and IL-12 production while reducing IL-10 and IL-6 levels, in addition to stimulating reactive oxygen species (ROS) and nitric oxide (NO) production, suggesting an immunomodulatory effect that contributes to parasite control. Molecular docking analyses revealed a favorable interaction between OG and trypanothione reductase (TR), while biochemical assays demonstrated reduced NADPH consumption, indicating interference with TR activity. Ultrastructural analysis revealed severe morphological alterations, including membrane disruption, cytoplasmic disorganization, mitochondrial swelling, and features consistent with apoptosis-like cell death. Conclusions: Collectively, these findings demonstrate that OG exhibits potent and selective trypanocidal activity associated with immunomodulatory effects, ultrastructural damage, and disruption of parasite redox metabolism through TR inhibition, supporting its potential as a candidate for future preclinical studies against Chagas disease. Full article

Long-term clinical translation of left ventricular assist devices (LVADs) is severely hampered by thromboembolism and device-related infection, both originating from inadequate biocompatibility of the device-blood interface. Current titanium surface modifications fail to simultaneously deliver durable antithrombotic and antibacterial performance, while conventional polydopamine-copper (PDA-Cu) coatings suffer from inherent limitations. Herein, we report a one-step rapid co-polymerization strategy based on mussel-inspired polyphenol chemistry to fabricate a copper-integrated polydopamine/tannic acid nanocoating on titanium (Ti/PDT(Cu)). By incorporating tannic acid rich in catechol/pyrogallol moieties, we achieve synergistic acceleration of dopamine oxidative polymerization with copper ions, dramatically shortening the fabrication time to 8 h (vs. 24 h for traditional PDA coatings). This process simultaneously constructs a robust dual-crosslinked network through covalent/hydrogen bonds and metal-phenolic coordination, exhibiting a uniform nanoscale-roughened structure. Comprehensive physicochemical characterizations confirm homogeneous coating deposition, excellent hydrophilicity, uniform Cu distribution, and superior long-term structural stability (95.68% thickness retention after 7 days of physiological immersion). The optimized coating displays broad-spectrum and durable antibacterial activity, with 92.79% and 89.73% reduction of E. coli and S. aureus at 24 h, respectively, and retains $>$89% antibacterial efficacy after 7 days of continuous elution (n = 3, * p$<$ 0.05). Moreover, the coating enables stable and sustained catalytic nitric oxide generation (43.85 $\pm$ 2.36 μM cumulative release over 14 days) that mimics endothelial function, resulting in 69.4% inhibition of platelet adhesion and an ultralow hemolysis ratio of 0.97% (n = 3). Critically, it maintains excellent cytocompatibility with L929 fibroblasts ($>$90% cell viability after 72 h co-culture). This work addresses key limitations of conventional PDA-based functional coatings, realizes synergistic antithrombotic and antibacterial dual functions showing great potential for blood-contacting cardiovascular device applications, and provides a facile and robust surface engineering platform for long-term implantable cardiovascular devices. Full article

Background/Objectives: Migraine is a common neurovascular disorder associated with substantial disability. Increasing evidence suggests that hypoxia-related signaling, endothelial dysfunction, and nitric oxide metabolism contribute to its pathophysiology. This study investigated the relationships between hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor A (VEGF-A), and arginine pathway metabolites in chronic migraine. Methods: In this observational study, fasting ethylenediaminetetraacetic acid (EDTA) plasma samples were obtained from 28 patients with chronic migraine and 28 healthy controls. Arginine, citrulline, and ornithine concentrations were quantified by liquid chromatography–tandem mass spectrometry, whereas HIF-1α and VEGF-A were measured using enzyme-linked immunosorbent assays. Group comparisons, receiver operating characteristic analyses, and Firth penalized logistic regression models were performed. Results: Patients with chronic migraine exhibited significantly higher VEGF-A and HIF-1α concentrations than controls (both FDR-adjusted p ≤ 0.001). VEGF-A demonstrated excellent discrimination of migraine status (AUC = 0.973), whereas HIF-1α showed good discriminatory performance (AUC = 0.794). The arginine-to-citrulline ratio was higher (FDR-adjusted p = 0.032) and ornithine concentrations were lower (FDR-adjusted p = 0.043) in migraine patients. In multivariable analyses, VEGF-A (OR = 14.46), HIF-1α (OR = 5.83), and ornithine (OR = 0.28) remained independently associated with migraine status. Conclusions: Chronic migraine was associated with elevated circulating HIF-1α and VEGF-A concentrations together with alterations in arginine metabolism. These exploratory findings suggest that hypoxia-responsive signaling, endothelial activation, and nitric oxide-related metabolic pathways may represent interconnected biological processes associated with chronic migraine. Larger longitudinal and externally validated studies are required to confirm these observations and clarify their potential clinical relevance. Full article

Staphylococcus aureus is an important zoonotic pathogen. In recent years, it has been isolated from diseased aquatic animals, causing skin ulcers and septicemia, establishing itself as an emerging pathogen in aquaculture. Rampant antibiotic use has accelerated antimicrobial resistance, a trend that has gradually curtailed the potency of conventional antibiotic therapies, underscoring the urgent need for novel therapies. Here, we screened 20 amino acids and found that exogenous proline significantly enhances the bactericidal activity of amikacin against S. aureus. This synergistic effect extends to other aminoglycoside antibiotics, including neomycin sulfate and gentamicin, and is also effective against drug-resistant strains such as MRSA USA300. Furthermore, we evaluated the efficacy of this combination in eradicating persisters and biofilms. Mechanistically, exogenous proline potentiates amikacin-mediated killing by modulating two key bactericidal pathways. On one hand, it enhances antibiotic uptake by augmenting the proton motive force via the electron transport chain. On the other hand, it amplifies oxidative stress through a multi-pronged mechanism involving the suppression of ROS-scavenging enzymes, activation of the Fenton reaction, and reduction in intracellular nitric oxide (NO) levels, ultimately culminating in bacterial cell death. This study proposes a promising strategy for combating S. aureus in aquaculture and healthcare-associated infections. Full article

Coleus Lour. and Plectranthus L’Hér. (Lamiaceae) species are recognized as promising sources of bioactive compounds for skin health, supported by their traditional use in skin-related conditions; however, scientific validation of these traditional uses remains limited for several species. In this work, the biological activities of eight Coleus and Plectranthus species (C. barbatus, C. cylindraceus, C. grandidentatus, C. hadiensis, C. madagascariensis, P. ambiguus, P. ecklonii, and P. fruticosus) were evaluated to support their ethnomedicinal relevance. Extracts were assessed for general toxicity (Artemia salina model), antimicrobial activity (well diffusion and microdilution methods) and antioxidant capacity (DPPH, TBARS and cellular assays). In addition, anti-inflammatory activity (ability to suppress nitric oxide), cytotoxicity in skin cell lines (HaCaT and HFF-1) and inhibition of skin-related enzymes (elastase, tyrosinase and collagenase) were evaluated. Antibacterial activity was predominantly observed against Gram-positive bacteria, with no general toxicity observed. P. ambiguous and P. ecklonii showed moderate-to-high antioxidant activity, while anti-inflammatory effects were observed for C. hadiensis and C. madagascariensis and P. ambiguous. None of the extracts showed cytotoxicity. Enzyme inhibition assays highlighted C. cylindraceus and P. ecklonii. HPLC-DAD analysis confirmed the presence of rosmarinic acid. Overall, the findings support the traditional use of Coleus and Plectranthus species for skin-related conditions and highlight their potential as sources of bioactive compounds for dermatological and cosmeceutical applications. Full article

Acute liver failure (ALF) is characterized by a rapid decline in liver function, leading to metabolic and organ failure. This study employed liver metabolomics, Nuclear Factor kappa-B (NF-κB) signaling pathway analysis, and inflammatory factor profiling to investigate the therapeutic mechanisms of xanthoxylin in ALF. Xanthoxylin administration led to increased antioxidant levels and reduced markers of inflammation and tissue damage. Xanthoxylin downregulated the messenger RNA (mRNA) expression of Nitric Oxide Synthase (NOS), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), NF-κB, Inhibitor of NF-κB α (IκBα), and Toll-like receptor 4 (TLR4), and inhibited the protein expression of p-p38 and p-p65 while upregulating B-cell CLL/Lymphoma 2 (Bcl-2) and B-cell Lymphoma-x (Bcl-xl). Metabolomic analysis identified 41 differentially expressed metabolites, 20 of which showed strong correlations with pharmacodynamic parameters. These 20 candidate metabolite signatures are involved in amino acid and carboxylic acid metabolic pathways, with potential links to glycolysis and the tricarboxylic acid (TCA) cycle. Together, these findings suggest that xanthoxylin exerts therapeutic effects against ALF by modulating the IκBα/NF-κB signaling pathway and related metabolic pathways, providing a scientific basis for understanding its multi-target mechanism. Full article

Chiang Mai, Thailand, experiences seasonal fine particulate matter (PM_2.5) pollution associated with metabolic diseases, but the underlying mechanisms remain unclear. This prospective observational study compared plasma metabolomes of 25 healthy adults in Samoeng District, a highly affected area, between low and high PM_2.5 exposure seasons using proton nuclear magnetic resonance (¹H-NMR) spectroscopy. Twenty-six metabolites differentiating haze and non-haze seasons were identified using PLS-DA (VIP > 1.5). During the haze season, 11 were elevated, whereas 15 were decreased. Among the elevated metabolites, the top five—maleylacetoacetic acid, deoxyribose 5-phosphate, betaine, 3-hydroxyanthranilic acid, and 1-methyladenosine—were associated with inflammation, increased reactive oxygen species, nitric oxide inhibition, and altered amino acid metabolism. The top five decreased metabolites—deoxyguanosine, D-arabitol, glycerophosphocholine, ophthalmic acid, and oxaloacetic acid—were involved in several metabolic pathways, particularly those involved in energy metabolism. A total of 56 metabolic pathways were altered by high PM_2.5 exposure, including pathways related to amino acids, lipids, sugars, nucleotides, vitamins, and energy metabolism. High PM_2.5 exposure disrupts metabolites and pathways, inducing inflammation, oxidative stress, impaired lipid/energy metabolism, insulin resistance, and high blood pressure. These alterations may increase the risk of metabolic and cardiovascular diseases, with dysregulated metabolites serving as potential biomarkers. These findings highlight the molecular impact of air pollution in affected populations and may support preventive strategies and public health policy development in affected regions. Further studies are needed to clarify these findings. Full article