Search Results (2,153)

Background: Parthenocissus quinquefolia (Virginia creeper), widely distributed and used in Chile, lacks a systematic characterization of its bioactive components. This study synthesizes the evidence on the phytochemical composition and biological activities of P. quinquefolia, with emphasis on metabolites involved in redox regulation and inflammation. Methods: A systematic review was conducted following PRISMA 2020 guidelines. Searches were performed across four electronic databases, including original studies reporting antioxidant and anti-inflammatory effects. Results: Of 665 records identified, 14 studies met the inclusion criteria. Phytochemical analyses revealed phenolic compounds, particularly flavonoids (e.g., catechin, epicatechin, gallocatechin, epigallocatechin, quercetin, rutin, isoquercitrin, myricetin, luteolin, naringin) and stilbenes (e.g., ε-viniferin, miyabenol C). These metabolites exhibit antioxidant activity through ROS scavenging, metal chelation, and Nrf2/ARE activation. Anti-inflammatory effects were attributed to the downregulation of NF-κB, AP-1, and MAPK signaling, inhibition of NLRP3 inflammasome activation, and suppression of COX-2/iNOS expression. Conclusions: P. quinquefolia is a rich source of phenolic metabolites with robust antioxidant and anti-inflammatory mechanisms. The consistency of molecular responses across studies highlights its potential as a promising candidate for phytotherapeutic development targeting oxidative stress and inflammatory pathways. Full article

The transcription factor IRF5 maintains macrophages in the pro-inflammatory M1 state. We assessed the effects of siRNA-mediated knockdown of Irf5 on murine bone marrow-derived macrophages (BMDM) in M0, M1 and M2 states. Knockdown of Irf5 in M1 macrophages made them phenotypically similar to M2 macrophages, which was reflected in the decreased expression of the M1 marker iNOS, increased expression of the M2 marker CD206, increased mitochondrial content and respective morphological changes. Interestingly, the M2 phenotype was also affected by the reduction in Irf5. Using atomic force microscopy (AFM), we showed that Irf5 knockdown increases plasma membrane roughness, particularly in M2 macrophages. AFM-based stiffness measurements indicated that Irf5 knockdown altered macrophage elasticity, potentially influencing their functional behavior. Our data suggest a complex role of IRF5 in macrophage polarization, supporting its dual role as a transcriptional activator and repressor both in M1 and M2 states, and highlight the importance of IRF5 in the maintenance of metabolic and functional properties of macrophages. Full article

Triterpenoids with diverse structural features have shown considerable potential as pharmaceutical precursors for anti-inflammatory therapies. Beesioside O (BO), a representative triterpenoid (cycloartane triterpene saponin), has previously been reported to exhibit notable anti-HIV and anticancer activities. However, its anti-inflammatory mechanisms have not been fully elucidated. In this study, we investigated the anti-inflammatory activity and underlying molecular mechanisms of BO in LPS-induced RAW264.7 macrophages. In addition, NP AI Engine predictions, molecular docking, density functional theory (DFT) calculations, and molecular dynamics simulations were conducted to characterize the anti-inflammatory properties of BO further. The experimental results indicated that BO inhibited the mRNA expression levels of iNOS and COX-2. Moreover, it can regulate the phosphorylation of ERK at 3 h. Potential signaling pathways and targets were subsequently analyzed. The structural and electronic properties of BO were calculated using the B3LYP/6-311+G (d,p) basis set. The BO–ERK2 kinase complex was also constructed for simulation. Furthermore, a BO derivative was prepared through hydrolysis followed by acylation, and its anti-inflammatory activity was evaluated. Overall, this study provides deeper insight into the anti-inflammatory effects of BO and supports its potential for further development as an anti-inflammatory agent. Full article

Juvenile scleroderma (JS), comprising localized (JLSd) and systemic (JSSc) forms, is a rare autoimmune disorder. This study investigated associations of polymorphisms in extracellular matrix (MMP1, MMP9) and vascular homeostasis (NOS3) genes with JS risk and immunological phenotypes. A case–control study involved 215JS patients (194 JLSd, 21 JSSc) and 72 controls. SNPs (MMP1 rs1799750, MMP9 rs3918242, NOS3 rs1799983) were genotyped using real-time PCR followed by minisequencing and mass spectrometric analysis of reaction products. Associations with disease risk, subtypes, and immunological markers were analyzed statistically. The MMP9 (rs3918242) CT genotype was significantly associated with JLSd (OR = 2.23, 95% CI: 1.14–4.37, p = 0.022), showing a trend in linear facial forms. The NOS3 (rs1799983) GG genotype demonstrated a trend toward association with JSSc (OR = 2.61, 95% CI: 0.92–7.37, p = 0.065). No significant associations were found for rs1799750 MMP1 and risk of disease development. The MMP9 risk genotype did not correlate with scleroderma-specific autoantibodies, while the NOS3 GG genotype was associated with lower serum levels of anti-collagen IV antibodies (p = 0.039). Genetic associations differ for JS subtypes: MMP9 with JLSd and NOS3 with JSSc. Children with CT polymorphism MMP9 (rs3918242) and with NOS3 (rs1799983) GG genotype were found to be genetically predisposed for the development of JS. Full article

Mangosteen (Garcinia mangostana L.) has long been used in traditional Southeast Asian medicine to treat inflammatory-related conditions. In this study, three new compounds, including garcimangone A (1), garcimangone B (2), and the S-form of garcimangone C (3), and 18 known compounds were isolated and investigated for their anti-inflammatory properties and effects on M1- and M2-associated markers. Among the isolated components, γ-mangostin (5), garcinone D (6), morusignin J (15), and fuscaxanthone C (16) showed the most potent NO-inhibitory effects in LPS-stimulated RAW264.7 cells. SAR study revealed that chromeno moiety at C-3,4, oxygen substituents at C-1,3,6,7, and isoprenyl groups at C-2,8 are key structural features that promoted anti-inflammatory activity. Cytokine analysis results indicated that morusignin J (15) and fuscaxanthone C (16) could modulate the production of pro-inflammatory cytokines, such as TNF-α and IL-6, while modulating the anti-inflammatory cytokine IL-10. Western blot results demonstrated that morusignin J (15) modulated the inflammatory response through NF-κB and MAPK signaling and increased the expression of M2-associated markers KLF4 and arginase-1 in LPS-induced RAW264.7 macrophages. Further molecular docking analysis confirmed the high binding affinity of morusignin J (15) with key iNOS residues, such as Gln257, Pro344, Glu371, and Hem901, and the in silico prediction supported its potent oral bioavailability and drug-likeness. These in vitro and in silico findings highlight that pericarps of G. mangostana possess potential as promising natural sources for functional extracts and bioactive constituents for the development of antioxidative and anti-inflammatory candidates, and warrant further in vivo investigation in the future. Full article

Olive pomace (OP), a by-product of olive oil production, is a sustainable resource rich in bioactive compounds with potential applications in cosmetics and pharmaceuticals. This study investigates the protective effects of olive pomace juice (OPJ) against H₂O₂-induced neuronal damage and LPS-induced inflammatory responses in HT22 and BV2 cells, respectively. OPJ suppressed H₂O₂-induced cell death and exerted anti-apoptotic effects by reducing the BAX/BCL2 ratio and caspase-3 cleavage. OPJ also mitigated neurodegenerative hallmarks by decreasing amyloid fibrils formation and inhibiting β-secretase and acetylcholinesterase (AChE) activity. Mechanistically, OPJ enhanced antioxidant response by upregulating Nrf2 and its downstream molecule HO-1, along with increasing mRNA levels of antioxidant enzymes, including catalase, SOD1, and GPx. OPJ further activated AMPKα–SIRT1–PGC1α signaling and CREB–BDNF–TrkB signaling, suggesting modulation of key antioxidant, anti-apoptotic, and neurotrophic pathways. In BV2 cells, OPJ downregulated pro-inflammatory cytokines (IL-6 and IL-1β) and decreased iNOS and COX-2 expression through suppression of NF-κB and MAPK signaling pathways. HPLC analysis identified hydroxytyrosol (10.92%) as the major active compound in OPJ, which compared with tyrosol (2.18%), and hydroxytyrosol exhibited greater neuroprotective and anti-inflammatory effects than tyrosol. This study highlights the potential of OPJ and its major compound, hydroxytyrosol, as functional agents for mitigating neurodegeneration-related cellular response, supporting its application in the food and pharmaceutical industries. Full article

ATP-dependent chromatin remodeling complexes regulate gene expression by altering chromatin structure through ATP hydrolysis. They are classified into four families—SWI/SNF, ISWI, CHD, and INO80—which remodel chromatin via nucleosome sliding, eviction, assembly, and editing to control transcription. These complexes play critical roles in DNA repair, tumorigenesis, and organogenesis. Recent advances in low-input proteomics have highlighted their importance in vertebrate embryonic development. In mammals, they regulate embryonic genome activation, lineage specification, and stem cell fate determination. In non-mammalian models (e.g., Xenopus laevis), they function from blastocyst formation to pre-organogenesis stages (gastrulation and neurulation)—key windows for chromatin reprogramming and cell fate decisions. This review provides a systematic overview of chromatin remodeling complexes, detailing their classification and conserved mechanisms, and discusses their functions in early embryogenesis and embryonic stem cell maintenance. The collective evidence underscores the implications of these chromatin remodelers for understanding developmental defects and advancing regenerative medicine. Full article

Parkinson’s disease is a neurodegenerative disorder that affects the elderly population worldwide. Rotenone (ROT) is an environmental toxin that impairs mitochondrial dynamics by inhibiting respiratory chain complex I and thus inducing oxidative stress. Farnesol (FSL) is a dietary sesquiterpene with antioxidant and anti-inflammatory properties reported in various in vivo models. To evaluate the efficacy of FSL in the management of PD, Wistar rats were injected with ROT (2.5 mg/kg, i.p) and pretreated with FSL. Immunohistochemical staining measured tyrosine hydroxylase-positive cells in the substantia nigra and striatum. Western blotting was employed to determine protein expression of inflammatory, apoptotic, and autophagic markers. Our results indicate that FSL significantly protected against ROT-induced inflammation by suppressing microglial and astrocytic activation through the downregulation of Toll-Like receptor 4 (TLR4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inhibitor of kappa B (IkB), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX), matrix metalloproteinase-9 (MMP-9) expression. FSL has also demonstrated an antioxidant effect by enhancing the activity of superoxide dismutase and catalase while reducing the level of Malondialdehyde and nitric oxide. Moreover, it restored homeostasis in ROT-induced imbalance between pro- and anti-apoptotic proteins. Impaired autophagy observed in ROT-injected rats was corrected by FSL treatment, which upregulated phosphorylated mammalian target of rapamycin (p-mTOR) expression and downregulated P62, an autophagosome marker. The protective effect of FSL was further supported by preserving the brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase in the brain. These findings demonstrate the neuroprotective ability of FSL and its potential to be developed as a pharmaceutical or nutraceutical agent for the prevention and treatment of PD by mitigating neuropathological changes observed in dopaminergic neurodegeneration. Full article

Brown algae of the Cystoseira genus are recognized as valuable sources of bioactive compounds, including polysaccharides. Within the framework of current restoration efforts regarding damaged Ericaria amentacea populations in the Mediterranean Sea, the valorization of apices derived from ex situ cultivation waste represents a sustainable opportunity for industrial and biomedical applications. In this study, sodium alginate (SA) was extracted from E. amentacea apex by-products using a hydrothermal–alkaline method and subsequently chemically characterized. FTIR analysis showed O-H, C-H, and COO- stretching compatible with commercial alginates, while 1H-NMR spectroscopy indicated high β-D-mannuronic acid content, with an M/G ratio of 2.33. The extracted SA displayed a molecular weight of 1 × 10⁴ g/mol and a polydispersity index of 3.5. The bioactive properties of the SA extract were investigated in chemico and in vitro. SA exhibited remarkable antioxidant activity, showing significant DPPH and nitric oxide-radical-scavenging capacity. Furthermore, SA demonstrated a strong anti-inflammatory effect in LPS-stimulated macrophages through modulation of several inflammatory mediators (i.e., IL-6, IL-8/CXCL5, MCP-1, and TNF-α). In particular, SA promoted a striking iNOS gene expression inhibition, which, paired with its direct NO-scavenging ability, paves the way for future pharmacological use of E. amentacea derivatives, particularly if sustainably obtained from restoration activity waste. Full article

Background: Due to chronic venous insufficiency, venous leg ulcers (VLUs) develop as chronic wounds characterized by impaired healing, persistent inflammation, and endothelial dysfunction. Nitrosative stress, mitochondrial damage, and tissue apoptosis caused by excess nitric oxide (NO) produced by iNOS in macrophages and fibroblasts are contributing factors in the chronic wound environment; therefore, pharmacological modulation of iNOS presents an attractive mechanistic target in chronic wound pathophysiology. Methods: Herein, we present the use of a structure-based computational strategy to assess the inhibition of tavaborole, a boron-based antifungal agent, against iNOS using human iNOS crystal structure (PDB ID: iNOS) by molecular docking using AutoDock 4.2, 500 ns simulation of molecular dynamics (MD), with equilibration within ~50 ns and analyses over full trajectory and binding free energy calculations through the MM-PBSA approach. Results: Docking studies showed favorable binding of tavaborole (–6.1 kcal/mol) in the catalytic domain, which stabilizes contacts with several key residues (CYS200, PRO350, PHE369, GLY371, TRP372, TYR373, and GLU377). MD trajectories for 1 ns showed stable structural configurations with negligible deviations (RMSD ≈ 0.44 ± 0.10 nm) and hydrogen bonding, and MM-PBSA analysis confirmed energetically favorable complex formation (ΔG_binding ≈ 18.38 ± 63.24 kJ/mol) similar to the control systems (L-arginine and 1400W). Conclusions: Taken together, these computational findings indicate that tavaborole can stably occupy the iNOS active site and interact with key catalytic residues, providing a mechanistic basis for further in vitro and ex vivo validation of its potential as an iNOS inhibitor to reduce nitrosative stress and restore endothelial homeostasis in venous leg ulcers, rather than direct therapeutic proof. Full article

During the COVID-19 pandemic, the prevalence of death in men was higher than in women. Using transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE2), we demonstrated that SARS-CoV-2 infects Leydig cells and uses its steroidogenic machinery for replication. This study investigates the impact of SARS-CoV-2 in the seminiferous epithelium of K18-hACE2 mice, focusing on the immune response, junctional proteins, and spermatogenesis. The seminiferous tubules (STs) and epithelial (EA) areas were measured. The number of Sertoli cells (SCs), spermatocytes, and damaged ST was quantified. Ultrastructural analysis was performed under transmission electron microscopy. Angiotensin II levels and immunolocalization of hACE2, spike, and nucleocapsid were evaluated. TUNEL and immunoreactions for Ki-67, TNF-α, INF-γ, iNOS, NF-κB, and Conexin-43 were performed and correlated with Jam-α, Stat1, Stat3, and iNOS expressions. hACE2, spike, and nucleocapsid immunolabeling were detected in the epithelium along with high angiotensin II levels in the infected mice. The infection caused a significant reduction in ST, EA, spermatocytes, SCs, Ki-67+ cells, Cx43 immunoexpression, and Jam-a expression. In the epithelium, TNF-α, IFN-γ, iNOS, and nuclear NF-κB immunolabeling increased along with Stat1 upregulation. These findings, combined with the increased epithelial hACE2 and high angiotensin II levels, confirm epithelial responsiveness to the infection and explain the spermatogenic failure and impaired junctional proteins. The presence of viral particles, increased TNF-α immunolabeling, and apoptotic features in Sertoli cells suggests that these sustentacular cells are targets for viral infection in the epithelium, and, due to their extensive projections and ability to phagocytize dying infected germ cells, they may disseminate the viruses throughout the epithelium. Full article

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease often causing functional disability. Current therapies provide only temporary relief and can cause adverse effects that frequently result in pain and disability. Current pharmacological options offer only temporary symptom relief and may cause adverse effects. Piper sarmentosum (PS), a plant traditionally used for its medicinal properties, has demonstrated antioxidant and anti-inflammatory activities that may counteract OA-related degeneration. This study provides preliminary insight into the therapeutic potential of PS aqueous extract in human OA chondrocytes. Methods: Compounds in the PS aqueous extract were profiled using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Primary human OA chondrocytes (HOCs) were treated with 0.5, 2, and 4 µg/mL of PS aqueous extract for 72 h. Key OA-related parameters were assessed, including anabolic markers (sulfated glycosaminoglycan (sGAG), collagen type II (COL II), aggrecan core protein (ACP), SRY-box transcription factor 9 (SOX9)), catabolic markers (matrix metalloproteinase (MMP) 1, MMP13, cyclooxygenase 2 (COX2)), oxidative stress (nitric oxide (NO) production, inducible NO synthase (iNOS) expression), and inflammatory responses (interleukin (IL) 6). Gene expression was quantified using qPCR, and protein levels were evaluated using the colorimetric method, immunocytochemistry, and Western blot. Results: A total of 101 compounds were identified in the extract, including vitexin, pterostilbene, and glutathione—bioactives known for antioxidant, anti-inflammatory, and chondroprotective functions. PS-treated chondrocytes maintain healthy polygonal morphology. PS aqueous extract significantly enhanced anabolic gene expression (COL2A1, ACP, SOX9) and sGAG production, while concurrently suppressing COX2 expression and NO synthesis. Additionally, PS aqueous extract reduced COX2 and iNOS protein levels, indicating inhibition of the NO signaling pathway. Catabolic activity was attenuated, and inflammatory responses were partially reduced. Conclusions: PS aqueous extract exhibits promising chondroprotective, antioxidant, and anti-inflammatory effects in human OA chondrocytes, largely through the suppression of NO-mediated catabolic signaling. The presence of multiple bioactive compounds supports its mechanistic potential. These findings highlight PS aqueous extract as a potential therapeutic candidate for OA management. Further ex vivo and in vivo studies are warranted to validate its efficacy and clarify its mechanism in joint-tissue environments. Full article

Chronic sleep deprivation (CSD) disrupts redox homeostasis and enhances neuroinflammatory activation, contributing to progressive cognitive impairment. Propyl gallate (PG), a lipophilic ester of gallic acid with established antioxidant activity, has not been investigated in the context of prolonged sleep deprivation. The current study examined whether PG alleviates CSD-induced oxidative imbalance, inflammatory activation, and associated behavioral deficits. Male ICR mice were subjected to 14 days of CSD using a rolling-drum apparatus and received oral PG (50, 100, or 200 mg/kg) or Ginkgo biloba extract (GBE, 40 mg/kg). Behavioral outcomes were assessed through a battery of tests, including the open-field, novel-object recognition, step-through, and Morris water maze paradigms. Oxidative and inflammatory biomarkers were assessed in serum and hippocampus, and Western blotting quantified the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2). PG improved CSD-induced impairments in exploration, recognition memory, and spatial learning; restored antioxidant capacity; reduced lipid peroxidation; enhanced Nrf2-associated antioxidant signaling; and suppressed NF-κB-mediated inflammatory activation. These findings indicate that PG alleviates cognitive deficits induced by CSD through the modulation of redox homeostasis and neuroinflammatory responses, supporting its potential as an antioxidant derivative under chronic sleep-deprivation conditions. Full article

Inflammation plays a central role in the pathogenesis of numerous diseases through the excessive production of nitric oxide (NO), prostaglandins, and pro-inflammatory cytokines. Although bromophenols from marine algae and various phenolic compounds exhibit strong anti-inflammatory activity, the biological properties of brominated vanillin derivatives remain largely unexplored. This study aimed to investigate the anti-inflammatory effects of 2-bromo-5-hydroxy-4-methoxybenzaldehyde (2B5H4M), a brominated vanillin derivative structurally similar to marine bromophenols, in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. 2B5H4M significantly reduced LPS-induced NO and PGE₂ production by suppressing the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). It also downregulated the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Mechanistically, 2B5H4M inhibited the phosphorylation and degradation of IκB-α, thereby preventing NF-κB nuclear translocation, and reduced the phosphorylation of ERK and JNK. These findings demonstrate that 2B5H4M exerts potent anti-inflammatory effects by simultaneously blocking NF-κB and MAPK signaling pathways. Although not algae-derived, the structural resemblance of 2B5H4M to marine bromophenols highlights its potential as a marine-inspired reference compound. This work suggests that 2B5H4M may serve as a promising lead scaffold for developing new phenolic anti-inflammatory agents and provides a foundation for future mechanistic and in vivo studies. Full article

Salmonella typhimurium (S.T) infection of the central nervous system (CNS) induces severe inflammation, leading to elevated expression of inducible nitric oxide synthase (iNOS) in microglia. This process catalyzes excessive production of nitric oxide (NO), resulting in irreversible damage to neuronal mitochondria. Asiatic acid (AA) is a small molecule with neuroprotective potential; however, its ability to counteract nerve injury induced by S.T and the underlying mechanisms remain unclear. In this study, we established an S.T-infected mouse model (in vivo) and an S.T-stimulated microglial model using BV-2 cells (in vitro) and employed techniques including immunofluorescence (IF), Western blot, co-immunoprecipitation (Co-IP), and RNA extraction and quantitative reverse transcription PCR (RT-qPCR) to systematically evaluate the protective effects and mechanisms of AA. The results showed that pre-treatment with AA significantly reduced the expression of iNOS and the production of NO caused by S.T infection in mouse hippocampal tissue and BV-2 cells. Mechanistically, AA exerts its effects by inhibiting the upstream Toll-like receptor 2 (TLR2)/Notch and nuclear factor-κB (NF-κB) signaling axis. It interferes with the nuclear translocation of Notch and p65 proteins and their complex formation under S.T stimulation, thereby blocking downstream expression of iNOS and production of NO. This study reveals a novel mechanism by which AA alleviates infection-related neuroinflammation through targeting Notch-p65 interactions, providing a new theoretical basis for its clinical application. Full article