Search Results (1,837)

The present study involves the isolation, structural elucidation, and biological evaluation of eight compounds from Pouzolzia zeylanica. From the n-hexane and ethyl acetate extracts of the plant, eight compounds were successfully isolated and identified: oleanolic acid (1), ursolic acid (2), 2α-hydroxyursolic acid (3), 3β-O-acetyl-12-oleanen-28-oic acid (4), 5-hydroxy-6,7-dimethoxyflavanone (5), 4′-methoxytectochrysin (6), 3,4′,5,7-tetrahydroxyflavanone-3-O-L-rhamnopyranoside (7), and 3,3′,5,5′,7-pentahydroxyflavanone-3-O-L-rhamnopyranoside (8). These compounds were evaluated for in vitro antioxidant activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation inhibition (TBARS) assays, as well as anti-inflammatory activity via inhibition of nitric oxide (NO) production and the secretion of pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in RAW 264.7 macrophages. It was observed that compound 3 exhibited the strongest antioxidant activity with IC₅₀ values of 18.52 ± 1.50 µM (DPPH) and 10.34 ± 0.93 µM (TBARS), whereas compounds 2, 5, and 6 showed moderate to weak effects. Meanwhile, compound 8 demonstrated the most potent anti-inflammatory effect with IC₅₀ values of 16.25 ± 0.95 µM (NO inhibition), 12.97 ± 0.88 µM (TNF-α inhibition), and 22.52 ± 1.98 µM (IL-6 inhibition). Furthermore, in silico approaches were employed, including density functional theory (DFT) calculations to predict the antioxidant mechanisms of compounds 1 and 3 and molecular docking to assess the cyclooxygenase-2 (COX-2) and phosphodiesterase-4B (PDE4B) inhibitory potentials of compounds 4, 7, and 8. Computational results aligned well with experimental data, supporting the potential of these compounds as natural antioxidant and anti-inflammatory agents. Full article

Tylorrhynchus heterochaetus is an aquatic food with both edible and medicinal value in China. With a protein-rich body wall, it has strong potential for producing bioactive peptides. To explore its potential as a source of immunomodulatory peptides, in this study, flavor enzymes were selected as the optimal hydrolases, and the hydrolyzed products were subjected to ultrafiltration fractionation. The <3000 Da portion exhibited the most effective immune-stimulating activity in RAW 264.7 macrophages, enhancing phagocytosis and promoting the secretion of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) in a concentration dependent manner. Peptide omics analysis, combined with the activity and safety screened by bioinformatics, identified 43 candidate peptides. Molecular docking predicts that three novel peptides, LPWDPL, DDFVFLR and LPVGPLFN, exhibit strong binding affinity with toll-like receptor 4/myeloid differentiation factor-2 (TLR4/MD-2) receptors through hydrogen bonding and hydrophobic/π stacking interactions. Synthetic verification confirmed that these peptides were not only non-toxic to cells at concentrations ranging from 62.5 to 1000 µg/mL, but also effective in activating macrophages and stimulating the release of immune mediators. This study successfully identified the specific immunomodulatory peptides of the Tylorrhynchus heterochaetus, supporting its high-value utilization as a natural source of raw materials for immunomodulatory functional foods. 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

Eugenia pyriformis Cambess., popularly known as uvaia, is a native Brazilian species belonging to the Myrtaceae family that has attracted pharmacological interest due to its richness in bioactive secondary metabolites. Previous studies have reported antimicrobial and antioxidant activities of the essential oil obtained from its leaves, reinforcing its therapeutic potential. In this context, the present study aimed to extract and characterize the essential oil from E. pyriformis leaves cultivated in the mountainous region of Rio de Janeiro, Brazil, and to evaluate its anti-inflammatory potential through in vitro and in vivo models. Gas chromatography mass spectrometry (GC–MS) analysis revealed a predominance of sesquiterpene hydrocarbons, mainly γ-muurolene, δ-cadinene, and β-caryophyllene. The oil exhibited significant anti-edematogenic activity in carrageenan-, prostaglandin E₂-, and bradykinin-induced paw edema models in adult female Swiss mice, suggesting modulation of inflammatory mediators, possibly through inhibition of the cyclooxygenase (COX) pathway. Conversely, no effect was observed in the compound 48/80-induced model, indicating the absence of activity on histamine- and serotonin-mediated processes. In vitro assays demonstrated that the oil reduced TNF-α and IL-1β gene expression in RAW 264.7 macrophages, confirming its ability to modulate pro-inflammatory cytokines. Taken together, these findings demonstrate that the essential oil of E. pyriformis exerts anti-inflammatory activity through multiple targets. Full article

Marine-derived fungi have become a vital resource for the discovery of novel secondary metabolites with diverse structures and significant biological activities. This study focuses on a systematic chemical investigation of the sponge-associated fungus Talaromyces stipitatus HF05001, leading to the isolation and identification of 20 compounds, including one new marine ketal natural product (Compound 17, Talarobispiral A). These compounds were structurally elucidated using comprehensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS. All isolates were screened for their anti-inflammatory and anti-adipogenic properties. Among them, compound 4 (Secalonic acid D, SAD), 7 (Sch 725680) and 16 (bacillisporins C) demonstrated significant anti-inflammatory potential by markedly suppressing nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Notably, compound 4 showed superior inhibitory effect, with an IC₅₀ value of 0.22 μM. Additionally, compound 4 exhibited the strongest dose-dependent inhibition of lipid droplet accumulation in 3T3-L1 preadipocytes. These findings highlight the dual therapeutic potential of metabolites from Talaromyces stipitatus, identifying promising lead compounds for the development of novel treatments for inflammatory and metabolic disorders. Full article

Norovirus is associated with vomiting and diarrhea and, in severe cases, can result in death. Currently, there is no effective treatment or vaccine for this virus. Bilateral interactions have been reported between gut microbiota and viral infection. Our laboratory has been studying the Surface layer protein A (SlpA) of a human isolate of Lactobacillus acidophilus. Previously, we reported that SlpA induces a variety of antiviral genes in human dendritic cells, suggesting it may prevent viral replication. SlpA binds to its cognate receptor SIGNR3-expressed on limited dendritic cells. To achieve a homogenous expression of the gene, we modified murine macrophage RAW 264.7 (RAW) cells by transducing SIGNR3-expressing lentivirus, resulting in RAWS cells. These cells and wild-type RAW cells were pretreated with SlpA for one hour and infected with 1 MOI of murine norovirus (MNV). We report that RAWS cells, when treated with SlpA, enhance the antiviral program to prevent viral replication, as determined by quantitative real-time PCR and viral titer. RNA isolated from MNV-infected cells revealed an elevation in two critical antiviral genes, Iigp1 and Ifit1, in SlpA-treated RAWS cells, potentially preventing viral replication. Full article

Alpha-lipoic acid (ALA) is a naturally occurring organosulfur compound with antioxidant and anti-inflammatory activities. The time-dependent effects of ALA and mechanism of interaction with cystathionine-γ-lyase (CSE—an enzyme responsible for hydrogen sulfide—H₂S synthesis) in RAW 264.7 macrophages remain unknown. In this study, we report results supporting the hypothesis that anti-inflammatory effects of ALA are associated with the reduction in CSE expression. To investigate the temporal effect of ALA in lipopolysaccharide (LPS—a potent stimulator of inflammation) treated RAW 264.7 macrophages, ALA was administered 1 h before LPS stimulation and 1, 3, and 6 h post LPS stimulation. Effects of ALA on different inflammatory and oxidative stress biomarkers including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), catalase activity (CAT), and malondialdehyde (MDA) levels were investigated. LPS stimulation significantly increased TNF- α, IL-6, MCP-1, MDA levels, and CSE expression and decreased CAT activity compared with the control group (p < 0.05 to 0.0001). ALA treatment at 1000 µM significantly attenuated LPS-stimulated inflammatory response in the macrophages across different time points (p < 0.05 to 0.0001). Furthermore, we found that ALA treatment reduced the expression of CSE in both pre- and post-treated LPS-stimulated macrophages in a time-dependent manner. In conclusion, this study demonstrated for the first time that the protective effects of ALA are dependent on the reduction in CSE expression in LPS-stimulated RAW 264.7 macrophages. Full article

Background: Salmonella is a major zoonotic foodborne pathogen. Conventional poultry vaccines may present limitations in terms of efficacy, safety, and practicality. Objectives: This study focuses on enhancing the immunogenicity and improving the safety of a novel oral vaccination employing inducible toxin–antitoxin (TA) systems, which lead to self-destruction of virulent Salmonella Enteritidis. Methods: A Hok/Sok (HS) TA system was designed to induce cell death upon absence of arabinose. Point mutations were introduced to the Hok toxin promoter to moderate toxin production. A combination of HS and CeaB/CeiB (CC) TA systems was designed to induce cell death both in low di-cation levels or anaerobic conditions. Survival of Salmonella-carrying TA systems was tested in culture and in the Raw264.7 macrophage cell line. One-day old chicks were inoculated with Salmonella carrying the TA system to evaluate bacterial persistence and induction of a protective immune response. Results: Attenuation of the Hok toxin promoter prolonged bacterial survival in vitro. Salmonella carrying the combined TA systems was eliminated completely both in vitro and in inoculated chickens, eliciting high levels of antibodies and conferring protection against challenge with wild-type Salmonella. Conclusions: These findings highlight the potential of the adaptable TA-based vaccination platform to generate safe and efficacious Salmonella vaccines for poultry, contributing to reduced transmission in the food chain. Full article

Porphyromonas gingivalis (Pg), a keystone pathogen of chronic periodontitis, releases outer membrane vesicles (OMVs) that act as nanoscale vehicles to disseminate virulence factors within periodontal tissues and systemically beyond the oral cavity. Although Pg-OMVs are increasingly recognized as critical mediators of host–pathogen interactions, their effects on the differentiation and function of monocyte–macrophage/osteoclast lineage cells remain unclear. Here, we examined the impact of Pg-OMVs on the differentiation of RAW264.7 monocyte/macrophage-like cells into osteoclasts (OC) and/or macrophages (MΦ) in the presence of receptor activator of nuclear factor-κB ligand (RANKL). OMVs were isolated from Pg W83 and applied to RANKL-primed RAW264.7 cells using three distinct stimulation schedules: (1) simultaneous treatment with Pg-OMVs and RANKL at Day 0; (2) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 1; and (3) RANKL priming at Day 0 followed by Pg-OMV stimulation at Day 3. In all schedules, cells were cultured for 7 days from the initial RANKL exposure. Remarkably, simultaneous exposure to Pg-OMVs and RANKL (Schedule 1) markedly suppressed osteoclastogenesis (OC-genesis) while promoting M1 macrophage polarization. In contrast, delayed Pg-OMV stimulation of RANKL-primed cells (Schedules 2 and 3) significantly enhanced OC-genesis while reducing M1 polarization. These schedule-dependent effects were consistent with altered expression of osteoclastogenic markers, including dc-stamp, oc-stamp, nfatc1, and acp5. Importantly, a monoclonal antibody against OC-STAMP counteracted the Pg-OMV-induced upregulation of OC-genesis in Schedules 2 and 3. Furthermore, levels of Pg-OMV phagocytosis were inversely correlated with osteoclast formation. Finally, co-stimulation with RANKL and Pg-OMVs (Schedule 1) enhanced macrophage migratory capacity, whereas delayed stimulation with Pg-OMVs (Schedules 2 and 3) did not. Collectively, these findings indicate that Pg-OMVs exert stage-specific effects on the OC/MΦ lineage: stimulation at early stages of RANKL priming suppresses OC-genesis and promotes M1 polarization, whereas stimulation at later stages enhances OC-genesis without inducing M1 differentiation. Thus, Pg-OMVs may critically influence the fate of the OC/MΦ unit in periodontal lesions, contributing to disease progression and tissue destruction. Full article

Investigation of the roots of Tripterygium wilfordii Hook. f. resulted in the isolation of nine sesquiterpene pyridine alkaloids (SPAs), including four previously undescribed compounds 1–4. The structures of all compounds were elucidated by extensive spectroscopic analysis, including NMR and HRESIMS. In particular, compound 1 was found to possess an unprecedented cage-like ether moiety, representing the first report of such a structural feature within this class of alkaloids. All isolated compounds were evaluated for their anti-inflammatory activity using a lipopolysaccharide (LPS)-induced RAW264.7 macrophage model. Compounds 1, 2, and 4 exhibited significant inhibition of nitric oxide (NO) production, with IC₅₀ values of 7.14 ± 1.89, 8.55 ± 0.37, and 14.76 ± 0.39 μM. Furthermore, compounds 1 and 2 suppressed the secretion of key pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, in the same cellular model. These results not only enhanced the structural diversity of SPAs identified from T. wilfordii, but also highlight their potential as promising anti-inflammatory lead compounds. Full article

The worldwide incidence of neurodegenerative diseases (ND), such as dementia, has increased, and neuroinflammation is considered a crucial factor in the development of ND. Codium fragile is considered ocean waste in many countries; however, some countries, including Korea, consume it as a food resource. In this study, a major low-molecular-weight component and chemical marker, uracil, was isolated from the aqueous extracts of C. fragile (AECF); additionally, its content was measured through HPLC quantitative analysis. AECF and uracil were examined for their anti-inflammatory activities against lipopolysaccharide (LPS)-stimulated BV2 microglia and RAW264.7 macrophage cell lines under inflammation conditions. The results showed that AECF and uracil inhibited the production of pro-inflammatory cytokines by suppressing the NF-κB pathway. Full article

Selenium nanoparticles (SeNPs), a highly promising candidate as a nutrient fortificant and food additive, face challenges in stability and biosafety. These limitations hinder their application in the food industry. In this study, Ganoderma lucidum melanin (GLM) was utilized as a natural stabilizer. Three distinct types of GLM-stabilized SeNPs, termed GLM-SeNPs (S-GLM, D-GLM, and A-GLM), were subsequently synthesized via an ascorbic acid reduction method. The results showed that the prepared nanoparticles exhibited uniform particle size (55–75 nm) and good dispersibility. Among them, S-GLM possessed the highest selenium content (2598.90 mg/kg) and demonstrated the best stability. GLM-SeNPs significantly downregulated (p < 0.05) the mRNA expression of key pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and upregulated (p < 0.05) the mRNA expression of the anti-inflammatory factor IL-10 in LPS-induced RAW264.7 macrophages. A potential mechanism underlying this effect may be the suppression of the NF-κB signaling pathway. In addition, GLM-SeNPs exhibited potent inhibitory effects against common foodborne pathogens. This study explores a potential novel strategy for the high-value utilization of natural functional components in food systems. These preliminary findings suggest GLM-SeNPs may have application potential in areas like functional beverages and food preservation. Further research is warranted to validate their feasibility in real food systems. Full article

The Rhodomyrtus tomentosa (Aiton.) Hassk. berry is rich in structurally diverse polysaccharides with potential biological activity. However, its immunomodulatory properties remain understudied, limiting our current understanding of its functional significance. Two structurally distinct polysaccharides from Rhodomyrtus tomentosa (RTP-1 and RTP-2) were evaluated for immunostimulatory activity in RAW264.7 macrophages. Phagocytic function was assessed by neutral red assay, nitric oxide (NO) and reactive oxygen species were measured using the Griess assay and fluorescent probes, and cytokines (TNF-α, IL-6 and IL-1β) were quantified by enzyme-linked immunosorbent assay. Analysis of RNA-seq data using weighted gene co-expression network analysis revealed co-expression modules. The selected transcripts were independently validated by quantitative real-time PCR (RT-qPCR). The results showed that both polysaccharides enhanced phagocytosis, increased NO/ROS levels, and promoted cytokine secretion. Transcriptome results indicated that RTP-2 activated the MEturquoise co-expression module containing 222 hub genes, whereas RTP-1 was mainly associated with the MECyan module containing 49 hub genes. Module enrichment for RTP-2 revealed links with mitophagy–immune regulation, proteostasis/stress, and innate immune signaling. RT-qPCR further confirmed that in the RTP-2 group, Dram1 expression was upregulated approximately 121 times, Bmf1 expression was upregulated approximately 18 times, and Bnip3 was significantly downregulated, whereas Bnip3l expression remained unchanged. Overall, RTP-2 exhibited a more pronounced and coherent macrophage-stimulating profile in vitro, supporting its potential as a macrophage-targeted immunostimulatory ingredient. Full article

Fermented products have recently garnered substantial interest in both research and commercial contexts. Although probiotic fermentation is predominantly practiced with dairy, fruits, vegetables, and grains, its application to dual-purpose food-medicine materials like Ganoderma lucidum has been comparatively underexplored. In this study, Ganoderma lucidum fermented juice (GFJ) served as the substrate and was fermented with five probiotic strains. The optimal inoculation ratios—determined by employing a uniform design experiment—were as follows: Bifidobacterium animalis 6.05%, Lacticaseibacillus paracasei 9.52%, Lacticaseibacillus rhamnosus 6.63%, Pediococcus pentosaceus 21.38%, and Pediococcus acidilactici 56.42%. Optimal fermentation parameters established by response surface methodology included 24 h of fermentation at 37 °C, a final cell density of 5 × 10⁶ CFU/mL, and a sugar content of 4.5 °Brix. Experiments with RAW264.7 macrophages revealed that GFJ significantly promoted both phagocytic activity and nitric oxide (NO) secretion, indicating enhanced immune characteristics as a result of fermentation. Untargeted metabolomics profiling of GFJ across different fermentation stages showed upregulation of functional metabolites, including polyphenols, prebiotics, functional oligosaccharides, and Ganoderma triterpenoids (GTs)—notably myricetin-3-O-rhamnoside, luteolin-7-O-glucuronide, raffinose, sesamose, and Ganoderma acids. These increments in metabolic compounds strongly correlate with improved functional properties in GFJ, specifically heightened superoxide dismutase activity and immunomodulatory capacity. These results highlight an effective approach for developing functionally enriched fermented products from medicinal fungi, with promising applications in functional food and nutraceutical industries. 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