Search Results (2,239)

The ethanolic extract of the roots of Murraya exotica (Rutaceae) yielded twenty coumarins, including twelve previously undescribed compounds named exoticoumarins A–L (1–12; two biscoumarins, five coumarin hybrids, and five monomers). Their structures, including absolute configurations, were elucidated by a combination of NMR and HR-ESI-MS analyses, single-crystal X-ray diffraction, ECD exciton coupling, Mo₂(OAc)₄- and Rh₂(OCOCF₃)₄-induced ECD, comparison of experimental with calculated ECD spectra, and chemical hydrolysis. Anti-inflammatory evaluation in LPS-stimulated RAW264.7 macrophages identified exoticoumarins A and K (1 and 11) as potent inhibitors of nitric oxide (NO) production, with IC₅₀ values of 7.41 and 10.63 μM, respectively. Mechanistic studies revealed that 1 suppressed nitric oxide synthase (iNOS) expression at both transcriptional and translational levels, an effect associated with the inhibition of c-Jun N-terminal kinase (JNK) phosphorylation within the mitogen-activated protein kinase (MAPK) signaling pathways, without markedly affecting extracellular regulated protein kinases (ERK) 1/2 phosphorylation. These findings highlight exoticoumarin A (1) as a promising anti-inflammatory lead derived from M. exotica. Full article

In this study, we evaluated the physiological effects of fermented metabolites derived from puffed grains (z), fermented using Bacillus amyloliquefaciens NPKE6, a strain isolated from Korean water kimchi. In vitro assays showed that NPKE6-FM significantly increased antioxidant enzyme activities (SOD, CAT, GPx) and digestive enzyme activities (α-amylase, protease), suggesting its strong biofunctional potential. To confirm its in vivo efficacy, we established two inflammatory disease models—ulcerative colitis and liver injury—in male C57BL/6 mice. Colitis was induced by oral administration of 1% dextran sodium sulfate (DSS, 1 mL), while liver injury was induced by intraperitoneal injection of acetaminophen (APAP, 300 mg/kg) three times per week for 4 weeks. In disease-induced control groups, elevated serum biomarkers (AST, ALT, ALP) and reduced antioxidant activity were observed. Experimental groups received 10 or 50 mg/kg/day of NPKE6-FM for 4 weeks. Treatment significantly restored antioxidant enzyme levels and reduced inflammatory markers such as TNF-α and IL-6. In the colitis model, NPKE6-FM alleviated DSS-induced tissue damage, evidenced by improved colon length, weight, and histological scores. Gene expression analysis showed downregulation of iNOS and COX-2 in colon tissues and Akt and MCP-1 in liver, indicating molecular anti-inflammatory effects. Although liver histopathology did not show marked improvement, biochemical and gene expression results supported its protective role. In summary, NPKE6-FM demonstrated potent antioxidant and anti-inflammatory activities in vitro and in vivo, indicating its potential as a functional food additive to prevent or alleviate inflammatory conditions such as colitis and liver injury. Full article

This study developed a transdermal drug delivery system for Rheumatoid Arthritis (RA) using a dual-network hydrogel microneedle patch loaded with methotrexate nanocrystals (DHMN@MTX-NCs), and explored its synergistic therapy with Adalimumab (ADA) for a painless, long-acting, and targeted RA treatment. This study synthesized Methacrylated Hyaluronic Acid and Methacrylated Gelatin. MTX-NCs were prepared by solvent-antisolvent precipitation and incorporated into a dual-network hydrogel microneedle patch via centrifugal molding. Evaluations included pharmaceutical properties, mechanical strength, drug release, in vitro anti-inflammatory effects on RAW 264.7 cells, and therapeutic efficacy in a rat RA model. The experimental results show that the prepared MTX-NCs present a spherical shape, an average size of 325.72 nm, a PDI of 0.154, and a drug-loading capacity of 61.3%. The microneedle patch exhibited high puncture efficiency and suitable swelling. In vitro, DHMN@MTX-NCs combined with ADA most strongly inhibited macrophage migration, upregulated IL-10, and downregulated TNF-α, IL-1β, NO, iNOS, and COX-2. In vivo, both monotherapy and combination therapy reduced joint swelling, bone erosion, and histopathological damage. Ultimately, the study demonstrated the synergistic anti-inflammatory efficacy of DHMN@MTX-NCs combined with ADA, providing a novel, non-invasive, and targeted therapeutic strategy for RA. Full article

The McMurdo Dry Valleys (DVs) of South Victoria Land, Antarctica, constitute the largest ice-free region on the continent and one of Earth’s most Mars-analog environments. Their hyper-arid polar desert conditions offer a unique setting for investigating surface weathering and mineralogical processes under extreme climates. This study presents the first regional-scale mapping of alteration and crystalline weathering minerals across the McMurdo DVs. It uses Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) multispectral data; visible and near-infrared (VNIR) and shortwave infrared (SWIR) bands were analyzed through a Spectral Hourglass Workflow, endmember extraction, and spectral unmixing with Matched Filtering (MF) and Constrained Energy Minimization (CEM). Inter-algorithm consistency analysis between MF and CEM yielded 78.83% overall agreement with a Kappa coefficient of 0.75, indicating strong methodological consistency in mineral discrimination using ASTER VNIR+SWIR data. It should be noted that this agreement reflects internal algorithmic robustness rather than independent geological validation. Geological reliability is instead supported by documented field observations, lithological map comparisons, and spectral correspondence with the USGS spectral library. Validation employed documented field observations, lithological maps, and the USGS spectral library. Results reveal distinct spatial distributions of hematite-limonite/goethite, jarosite, kaolinite/smectite-illite-pyrophyllite-alunite, muscovite, hydrous silica/sericite/jarosite/hematite, epidote/chlorite, and calcite, closely associated with lithological units and unconsolidated deposits in Taylor, Wright, Victoria, and McKelvey Valleys. An inter-algorithm consistency check achieved 78.83% overall accuracy with a Kappa coefficient of 0.75, underscoring the robustness of ASTER VNIR+SWIR data for Antarctic mineral discrimination despite localized spectral mixing. Beyond refining the geological understanding of the McMurdo DVs, these results establish ASTER as an effective tool for regional mineralogical mapping in inaccessible polar terrains. The findings further strengthen the role of the Dry Valleys as a terrestrial analog for Mars, where similar mineralogical assemblages and spectral ambiguities have been observed, thereby contributing to both Antarctic geoscience and planetary exploration frameworks. Full article

Uncontrolled inflammation contributes to the development of neurodegenerative diseases (NDs) like Alzheimer’s disease (AD). N-(p-Coumaroyl) serotonin (CS) has demonstrated a significant capacity to modulate hyper-inflammation. We explored whether CS could mitigate inflammatory responses in endotoxin-challenged microglial cells and sought to elucidate the specific molecular mechanisms governing these effects. ELISA, nitric oxide (NO) assays, Western blotting and immunocytochemistry were performed to study inflammatory responses and related signal transduction mechanisms. CS pretreatment effectively attenuated the inflammatory output in endotoxin-primed microglial models. This was evidenced by a significant reduction in key cytokines (such as IL-6, TNF-α, and MCP-1) and a concomitant decrease in the protein levels of iNOS and COX-2. These effects were mediated through the disruption of MAPK/NF-κB signaling cascades and the sequestration of NF-κB within the cytoplasm. Beyond its anti-inflammatory role, CS promoted the HO-1/NQO1 signaling pathway and interfered with the LPS-mediated TLR4/MyD88 cascade. Our collective evidence indicates that the modulation of microglia-mediated inflammation by CS is underpinned by the suppression of MAPK/NF-κB and the induction of antioxidant systems, suggesting that CS may have the potential to improve NDs. Full article

Aspergillus flavus Link, 1809 is a pathogenic fungus widely present in the environment. It can infect plants and also acts as an opportunistic pathogen affecting humans and other animals. The aflatoxins (AFs), it produces, can cause cancers such as liver cancer. Therefore, in-depth research into the pathogenic mechanisms of A. flavus is crucial. Arp8 (Actin-like protein Arp8) is a unique subunit within the chromatin remodeling complex INO80, regulating processes including chromatin remodeling. However, the biological function of Arp8 in A. flavus remains unclear. This study constructed A. flavus arp8 knockout (Δarp8) and complementation (Com-arp8) strains via homologous recombination. Subsequent research revealed that following the deletion of arp8, A. flavus exhibits a reduction of approximately 51% in conidia production, complete abrogation of sclerotia formation, and significantly impairment of aflatoxin B1 (AFB1) biosynthesis. Crop grain colonization and Bombyx mori Linnaeus, 1758 infection models demonstrated that Arp8 plays a crucial role in A. flavus ability to infect hosts. Environmental stress experiments identified Arp8 as a vital factor for A. flavus in response to various environmental stresses. Quantitative RT-PCR (qRT-PCR) analysis indicated Arp8 achieves its biological functions through corresponding regulatory factors. This study elucidates the biological functions of Arp8 in A. flavus growth and development, pathogenicity, and aflatoxin synthesis, laying a foundation to illuminate the mechanisms of A. flavus pathogenicity and AFs production. Full article

Macrophage polarization is widely recognized as a pivotal role in the maintenance of liver homeostasis. Lysolecithin (LPC) has previously been associated with hepatoprotective effect. This study aimed to determine whether LPC protected against lipopolysaccharide (LPS)-induced liver injury by modulating macrophage polarization. Twenty-four piglets were allocated in a 2 × 2 factorial design, involving dietary supplementation (0 vs. 0.01% LPC) and immunological challenge (saline vs. LPS). Animals were euthanized 4 h post-injection, and liver tissues were harvested for analysis. Our findings showed that LPS challenge induced significant liver damage, which was ameliorated by LPC supplementation, as evidenced by improved histological and functional outcomes. LPC counteracted the LPS-induced dysregulation of mRNA expression related to macrophage polarization, including pro-inflammatory markers (IL-6, IL-1β, TNF-α, IFN-γ, iNOS, and CD80) (p < 0.05). Furthermore, LPC restored the expression of key metabolic genes involved in glycolysis and the TCA cycle (HK2 and IDH) (p < 0.05). Mechanistically, LPC normalized the activation of the mTOR signaling pathway by modulating both mRNA and protein levels of mTOR, S6K1, and HIF-1α (p < 0.05). These findings suggest that LPC attenuates LPS-induced liver injury by influencing metabolic and inflammatory pathways, potentially through the inhibiting M1 polarization mediated by glycolysis-related mTOR signaling pathways. Targeting macrophage polarization by LPC may represent a promising therapeutic strategy for inflammatory liver conditions. Full article

Perennial ginseng (Panax ginseng) has long been valued for its medicinal properties. However, ginseng sprouts are gaining prominence as a versatile food source due to the high levels of bioactive compounds in their leaves and stems. To further enhance their functional value, this study investigated the effects of fermentation using lactic acid bacteria, specifically Lactobacillus and Enterococcus strains, on the antioxidant and anti-inflammatory potential of ginseng sprout extract (GSE). Chemical analyses revealed that fermentation significantly increased total phenolic content (TPC) and ginsenoside Rb₁ levels, which were associated with enhanced radical-scavenging activity and superoxide dismutase (SOD)-like activity. In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, fermented GSE (FGSE) exhibited significantly greater anti-inflammatory effects than non-fermented GSE. This enhancement was evidenced by marked downregulation of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E₂ (PGE₂), along with their corresponding enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Notably, the anti-inflammatory profile of FGSE was distinguished by its ability to suppress specific cytokines that were not significantly affected by GSE. Although both GSE and FGSE attenuated interleukin-1beta (IL-1β) and interleukin-6 (IL-6), only FGSE achieved statistically significant inhibition of tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). These findings indicate that fermentation is a critical process for surpassing the efficacy threshold of GSE against key inflammatory signals. Overall, the enrichment of bioactive metabolites during fermentation suggests that FGSE can serve as a potent functional ingredient for modulating inflammatory responses, with considerable potential for the development of advanced functional foods. Full article

Background: Atrial fibrillation (AF) is closely linked to endothelial dysfunction, yet its mechanisms remain unclear. Extracellular vesicles (EVs), including exosomes, are released by most cell types and mediate intercellular communication. We therefore investigated the role of EVs in endothelial dysfunction associated with AF. Methods: Vascular endothelial function in patients with sinus rhythm (SR), premature ventricular contractions (PVCs), or AF was assessed by peripheral arterial tonometry. Plasma-derived EVs were isolated from these three groups. Conditioned medium was collected from cultured cardiomyocytes (CMs), which were paced either regularly or irregularly at 1 Hz or 10 Hz or were non-paced, and EVs were subsequently isolated from the conditioned media. The isolated EVs were applied to endothelial cells (ECs), and mRNA levels of vasoactive genes were quantified. Results: The reactive hyperemia index (RHI) was significantly lower in patients with AF than in those with SR (RHI values: 1.98 in SR vs. 1.57 in AF, p = 0.049), whereas no significant decrease was observed in patients with PVCs, indicating endothelial dysfunction in AF. The plasma EV concentration was significantly higher in patients with AF than in those with SR. CMs subjected to 10 Hz irregular pacing released more EVs than non-paced cells and cells under 1 Hz regular pacing. When applied to ECs, EVs from patients with AF and from rapidly paced CMs significantly reduced NOS3 mRNA expression in vitro. Conclusions: Circulating EVs are increased in AF and could be associated with an impaired endothelial function in AF. Full article

Background/Objectives: During oral and gut microbiota dysbiosis, lipopolysaccharides (LPSs) of major bacteria, such as Porphyromonas gingivalis and Escherichia coli, translocate into the bloodstream and lead to endotoxemia. Cerebral endothelial cells are targets of LPSs that may aggravate inflammation and cerebrovascular disorders. This study aimed to evaluate the protective role of the characterized polyphenol-rich extract of the Dodonaea viscosa medicinal plant and a predominant component, epicatechin, on murine bEnd.3 cerebral endothelial cells exposed to P. gingivalis or E. coli LPSs. Methods: The effects of LPSs and polyphenols were assessed on cell viability (MTT, trypan blue exclusion assays) and inflammatory, redox, vasoactive and permeability markers (RT-qPCR, Western blot, ELISA, FITC-Dextran test). Results: The data show that LPSs activated the TLR2-4/NFĸB signaling pathway and promoted IL-1β, IL-6, TNF-α, MCP-1, COX-2, iNOS, ICAM-1, VCAM-1 and E-selectin production without affecting cell viability. LPSs induced oxidative stress by elevating intracellular ROS levels and altering the expression of genes encoding NOX2-4, SOD, catalase, GPx, HO-1 and Nrf2. LPSs imbalanced NO vasodilator and ET-1 vasoconstrictor levels and reduced the production of occludin and ZO-1 tight junction proteins. Meanwhile, LPSs raised the permeability to FITC-Dextran, suggesting cell integrity loss. The extent of endothelial dysfunction caused by LPSs depended on their bacterial origin. Importantly, plant polyphenols and epicatechin exerted anti-inflammatory and antioxidant effects, and attenuated LPSs’ deleterious action on vasoactive and permeability markers. Conclusions: This study shows that polyphenols limit cerebral endothelial cell dysfunction under inflammatory conditions mediated by LPSs, highlighting their therapeutic potential in protecting brain homeostasis during oral and gut microbiota dysbiosis. Full article

Excessive right heart load imposes an acute or chronic injury on the right ventricle (RV), predisposing critically ill neonates and cardiac surgical patients to RV failure, low cardiac output syndrome, and death. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that improves ventilation–perfusion matching and unloads the RV without systemic hypotension; nonetheless, its application beyond established neonatal indications remains contentious. Our review synthesizes current mechanistic, translational, and clinical evidence regarding iNO use in three major settings characterized by excessive RV load: (1) neonatal pulmonary hypertension, particularly PPHN; (2) acute and chronic RV overload in older children and adults, including secondary pulmonary hypertension, acute respiratory distress syndrome (ARDS), and acute pulmonary embolism; and (3) perioperative and post-cardiopulmonary bypass (CPB) management in congenital and adult cardiac surgery. In term and near-term infants with hypoxic respiratory failure, pivotal randomized trials show that iNO consistently improves oxygenation and reduces extracorporeal membrane oxygenation (ECMO) use, but this has little effect on survival and long-term neurodevelopment. In ARDS and other adult critical-care indications, iNO provides transient improvements in gas exchange and RV performance without reducing mortality or ventilator duration, and meta-analyses signal an increased risk of acute kidney injury, particularly with prolonged use. In contrast, perioperative studies around CPB demonstrate that prophylactic postoperative iNO and intra-CPB nitric oxide administration can attenuate pulmonary hypertensive crises, facilitate separation from CPB, shorten ventilation and intensive care stay, and, in selected high-risk cohorts, may reduce cardiac surgery-associated acute kidney injury, although survival benefits remain unproven. Across these scenarios, iNO should be used judiciously and in a pathophysiology-driven manner as a time-limited, targeted adjunct to stabilize patients with documented or anticipated RV strain rather than a disease-modifying therapy. Future work should refine patient selection, timing, dosing, and weaning strategies, and define the long-term safety and cost-effectiveness of iNO within contemporary multimodal RV support pathways. Full article

Recovery of nutritional and bioactive molecules by pomegranate peel (PP) has found wide applications in food and pharmaceutical industries. We investigated protective effects of a PP extract (PPE) from Mediterranean (Mazara del Vallo, Italy) on intestinal inflammation by using in vitro and ex vivo models. Reactive oxygen species (ROS) and lactate dehydrogenase (LDH) levels, as well as tight junction protein-1 (ZO-1) expression, were determined in lipopolysaccharide (LPS)-injured Caco-2 cells treated with PPE. We evaluated anti-inflammatory and antioxidant effects of PPE in isolated colon specimens of adult male mouse (C57/BL6) stimulated by LPS. Cyclooxygenase-2 (COX-2), nuclear factor-kB (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), as well as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), and inducible nitric oxide synthase (i-NOS) gene expression was determined. We also characterized phytochemical composition of the extract through chromatographic (HPLC-UV) and spectrophotometric techniques. PPE was rich in punicalagins A and B, along with other polyphenols such as hydroxytyrosol (HT), catechin, p-coumaric acid, and rosmarinic acid. In Caco-2 cells, PPE reduced ROS generation and LDH release, restoring intestinal barrier integrity by upregulating ZO-1 expression. In addition, PPE increased SOD, CAT, and GPX and suppressed COX-2, NF-kB, TNF-α, IL-1β and i-NOS LPS-induced gene expression in colon. PPE mitigates inflammation and oxidative stress, restoring intestinal barrier function. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to HT, rosmarinic acid, p-coumaric acid, catechin, as well as punicalagins A and B. Full article

Background/Objectives: Xanthones from the tropical fruit mangosteen (Garcinia mangostana) have been reported to modulate oxidative stress and inflammatory responses. This work explored the anti-inflammatory potential of mangosteen in the form of tinctures. Methods: Tinctures were prepared from the pericarp and leaves, characterized for their major constituents, and evaluated for their in vitro, anti-inflammatory and antioxidant potential. Results: HPLC analysis revealed eight major isoprenylated xanthones whose concentrations increased with an increasing alcohol percentage. α-Mangostin and γ-mangostin, two major xanthones present in the tinctures, were stable for 12 weeks at room and elevated (40 °C) temperatures, indicating stability of the tincture. In vitro luciferase reporter assays using HepG2-ARE revealed an alcohol concentration-dependent activation of Nrf2 by pericarp and leaf tinctures. The tinctures inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and reactive oxygen species (ROS) in RAW264.7 cells. Garcinone C (GarC) and garcinone D (GarD) caused significant inhibition of LPS-induced NO production and iNOS expression. GarC and GarD also induced nuclear translocation of Nrf2 and upregulated heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and glutathione S-transferase Pi 1 (GSTP1) in RAW264.7 cells. Conclusions: Taken together, mangosteen tinctures are a significant source of prenylated xanthones with anti-inflammatory and antioxidant potential. Full article

Bisacurone is a sesquiterpenoid constituent of Curcuma longa that has received considerably less attention than curcuminoids despite emerging evidence of its biological activity. In this study, the anti-inflammatory potential of bisacurone isolated from the Ryudai gold variety of Curcuma longa was evaluated using an integrated in vivo and in silico approach. Acute inflammation was assessed in rats using a carrageenan-induced paw edema model, supported by histopathological examination of paw tissues. Bisacurone significantly reduced paw edema during the peak inflammatory phase and markedly attenuated dermal thickening and inflammatory cell infiltration, indicating effective suppression of acute inflammatory responses. The effects of bisacurone were comparable to that of indomethacin. To elucidate the underlying molecular basis, density functional theory calculations, molecular docking, molecular dynamics simulations, and pharmacokinetic and toxicity predictions were performed. In silico analyses revealed favorable electronic properties, drug-likeness, and stable interactions of bisacurone with key inflammatory regulators, particularly IKKβ and COX-1, along with moderate interactions with MAPKs and iNOS. Molecular dynamics simulations confirmed the stability of the protein–ligand complexes. Collectively, these findings demonstrate that bisacurone exerts anti-inflammatory effects through multi-target modulation of inflammatory signaling pathways and highlight its potential as a bioactive functional food component and a lead compound for anti-inflammatory drug development. Full article

Severe respiratory inflammation or viral infections can lead to acute lung injury (ALI), a disease characterized by diffuse inflammatory injury of the pulmonary epithelium and endothelium. Cepharanthine (CEP) is reported as a promising drug candidate due to its antiviral properties. However, CEP exhibits poor solubility and low bioavailability. Therefore, we developed a novel liposome, named CEP@LP-M^CCR2, which integrates the advantages of cell membranes and lipid materials, to achieve effective accumulation of CEP in inflamed lungs. It exhibits a 1.73-fold increase in lung accumulation at 24 h in vivo, a 4.56-fold increase in cellular uptake in MLE-12 cells. CEP@LP-M^CCR2 is equipped with a CCR2-overexpressed surface, enabling it to selectively neutralize elevated levels of CCL2, which is related to ALI, thereby reducing macrophage infiltration, thereby reducing the spread of inflammation, such as a reduction in levels of key pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). CEP@LP-M^CCR2 could suppress M1 macrophage polarization, which led to a marked decrease in iNOS and an increase in Arg1. It upregulated the expression of junctional proteins E-cadherin and Occludin, indicating potential recovery of the pulmonary epithelial barrier. RNA sequencing analysis implied the potential of CEP@LP-M^CCR2 to inactivate the TNF/NF-κB signaling axis. Full article