Search Results (2,000)

Umami taste in lager beer not only determined body fullness and the backbone of aftertaste, but also affected the controllability and interpretability of flavor expression across the entire brewing process. Based on stage-wise sampling, peptidomic profiles were established on wort fermentation day 0, day 1, day 3, and day 9. A total of 25,592 peptides were identified by reversed-phase liquid chromatography–quadrupole time-of-flight mass spectrometry (RPLC-QTOF-MS). Molecular informatics screening was performed using UMPred-FRL (a feature representation learning-based meta-predictor for umami peptides) and TastePeptides-Meta (a one-stop platform for taste peptides and prediction models), yielding 7255 potential umami peptides. From these, 145 peptides were further selected for molecular docking. In addition, 6 representative umami peptides were selected for receptor-level validation and structural analysis. Mechanistically, the umami receptor taste receptor type 1 member 1/taste receptor type 1 member 3 (T1R1/T1R3) belonged to class C G protein-coupled receptor (GPCR) and relied on the extracellular Venus flytrap (VFT) domain for ligand capture. Ligand-induced VFT conformational convergence transmitted changes to the transmembrane region and triggered signal transduction. Docking and energy decomposition indicated that the ionic group primarily contributed to orientation and anchoring. Salt-bridge or hydrogen-bond networks were formed around Lys228, Arg240, Glu206, Asp210, Asn141, and Gln138, thereby reducing conformational freedom. Meanwhile, hydrophobic side chains obtained major binding gains within a hydrophobic microenvironment formed by Val135, Ile137, Leu165, Tyr166, Trp78, and His79. These results reflected a synergistic mode in which charge pairing enabled positioning and hydro-phobic complementarity promoted VFT closure. To experimentally confirm sensory relevance, 6 representative peptides were individually spiked into 4 brewing-stage beer samples, which produced a clear stratification pattern across stages. Notably, peptides with favorable docking-derived binding propensity did not necessarily enhance umami perception, and several longer peptides showed persistent negative sensory shifts, supporting that binding affinity alone could not be treated as a proxy for perceived umami in the beer matrix. At the node level, the cumulative abundance of umami peptides showed a significant positive correlation with umami scores, with a Pearson correlation coefficient of r = 0.963 and p = 0.037. This result indicated good linear consistency between umami peptide content and the upward shift in umami taste in lager beer. Umami peptide clusters were further proposed as a more appropriate functional unit, and an umami peptide cluster database spanning the full process was constructed. This database provided a reusable resource for process control and flavor prediction. Full article

Background: Chronic kidney disease (CKD) is increasingly prevalent, leading to more patients requiring hemodialysis. Medium cut-off (MCO) membranes, such as the ELISIO™ HX dialyzer, may enhance middle-to-large molecule removal and reduce inflammation compared with conventional high-flux membranes. This study evaluated the efficacy and safety of ELISIO™ HX versus a standard high-flux dialyzer (Toraylight NS-21S) in terms of molecular reduction rate and inflammation. Methods: We performed a single-center, prospective, randomized crossover study with 12 hemodialysis patients, each treated with Toraylight NS-21S and ELISIO™ HX over four weeks. Pre- and post-dialysis levels of urea, creatinine, albumin, creatine kinase, phosphorus, parathyroid hormone, C-reactive protein (CRP), procalcitonin, interleukin 6 (IL-6), and β2-microglobulin were measured. Pre–post differences were assessed using dialyzer analysis, period-effect and carryover analysis, and non-inferiority analysis. Results: ELISIO™ HX was non-inferior to Toraylight NS-21S for creatinine, urea, phosphorus, procalcitonin, and β2-microglobulin. No significant serum albumin changes were observed with either dialyzer. Adverse events were infrequent and comparable between the dialyzers. Conclusions: ELISIO™ HX appears non-inferior to Toraylight NS-21S and suggests good safety and tolerability. These findings should be interpreted with caution given the study’s limited power. Full article

Background: Diabetes mellitus is characterized by elevated blood sugar due to absolute or relative insulin deficiency. Diabetes is classified as type 1 (T1D) or type 2 diabetes (T2D), gestational diabetes, and other types, such as monogenic diabetes, exocrine pancreatic disorders, and medication-induced diabetes. Objectives: This review article provides an overview of diabetes genetics, covering polygenic, monogenic, and syndromic forms of the disorder with emphasis on aspects to help clinicians in diagnosis, management, and counseling, but also to foster valuable knowledge for diabetic researchers in identifying phenotypes that will help inform gene discovery. Key Findings: Most cases of T1D and T2D are polygenic with environmental triggers. T1D results from autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency. Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to T1D. Early studies showed a linkage between T1D and several human leukocyte antigen (HLA) susceptibility loci on chromosome 6. Genome-wide association studies (GWAS) have identified more than 100 HLA- and non-HLA loci that increase susceptibility to T1D. It has been well established that a substantial portion of the genetic risk for T1D is encoded in the HLA locus. The non-HLA loci INS, CTLA4, IL2RA, IFIH1, and PTPN22 make moderate contributions to T1D risk. Many other non-HLA loci have small effects to the phenotype and are relevant to autoimmunity, but they are yet to be identified. T2D, on the other hand, is associated with obesity and insulin resistance with relative insulin deficiency. Thousands of gene variants that are common and contribute small effects have also been identified through GWAS to contribute to T2D risk, but the rarer variants may confer significant risk to an individual’s risk. Common variants in the TCF7L2 locus consistently carry one of the largest risks associated with T2D with a reported 1.7-fold disease odds for homozygous carriers. The usefulness of individual variants for genetic counseling in the common forms of diabetes has been limited in clinical settings in the past. The development of polygenic risk scores (PRS) and partitioned polygenic risk scores (PPRS), statistics derived from GWAS, are being used to predict and classify diabetes. The performance of PRS and PPRS varies by ancestry and type of diabetes. The PRS performs better with T1D, with an area under the curve and receiver operating characteristics (AUC-ROC) ranging from 0.87 to 0.93, compared to 0.72–0.75 for T2D. The genetic architecture of T2D is markedly more polygenic than T1D, and the PPRS has been useful in assessing risk in that setting. Monogenic diabetes comprises several dysglycemic disorders that include neonatal diabetes, maturity-onset diabetes of the young (MODY), and other genetic syndromes that have diabetes either as an associated finding and/or as a complication. Some of the monogenic diabetes gene variants have incomplete penetrance and variable expressivity leading to different ages of onset and variable presentation even within the same family. Hence some patients with these conditions have been previously diagnosed as having T1D or T2D. Many monogenic disorders follow Mendelian inheritance patterns, so genetic counseling is relatively straightforward if pathogenic variants are found to be inherited from a parent. Counseling for forms of diabetes due to maternally inherited mitochondrial cytopathies, such as MELAS and Kearns–Sayres syndrome, is not straightforward due to the occurrence of two or more populations of genetically distinct mitochondrial DNAs in the cells (heteroplasmy); the higher the percent of pathogenic variants in a cell or tissue, the greater the chance for affectation of disorder. Implications: Early stages of diabetes may be asymptomatic, and improvement in methodologies to identify individuals at high risk is important so prevention strategies can be targeted to susceptible individuals to slow or obviate the onset of disease and to minimize complications. Conclusions: Diabetes is a heterogeneous disorder, and accurate definition of phenotypes in the setting of non-syndromic and syndromic forms, development of powerful statistical methodologies, use of next-generation sequencing applications to interrogate the genome, incorporation of epigenetic mechanisms in statistical modeling and accurate curation of gene variants, will help us to realize application of genomic medicine and to inform diabetes care. Full article

The purpose of this study was to evaluate the effect of early feeding with probiotic-fermented feed on growth performance, intestinal microbiota structure, immune responses, and gene expression. Two hundred and forty-one-day-old African ostrich chicks were randomly divided into three groups (eight replicates/group). The control group was fed a basal diet (CON), whereas the PELF3 and PELF6 groups were fed the probiotic-fermented feed for the first 3 or 6 days post-hatching, respectively, after which, all chicks were fed the basal diet for 56 days. The results showed that adding PELF3 or PELF6 significantly enhanced body weight gain and the feed conversion ratio. Chicks fed PELF had higher superoxide dismutase (SOD, p < 0.05), immunoglobulin A (IgA), and IL-10 levels and lower IL-6 and malondialdehyde (MDA, p < 0.05) levels than those fed CON. Plasma cholesterol, low-density lipoprotein (LDL), creatinine, uric acid, and alanine aminotransferase (ALT) levels decreased; however, high-density lipoprotein (HDL, p < 0.05) levels increased in the PELF groups. The addition of PELF reduced the pathogenic counts in the intestines of chicks (p < 0.05). Moreover, increased expression of IGF-1 and MUC-2 genes was observed in the PELF3 and PELF6 groups, whereas the expression of SLC15A1 increased in the PELF6 group. In conclusion, growth performance, immunity, gene expression, oxidative stability, and gut microbiota can all be significantly enhanced by early feeding with PELF. This study demonstrated an effective technique for applying early feeding of PELF in ostrich chicks. Full article

Ascending placentitis is a significant cause of equine pregnancy loss, yet the upstream inflammatory triggers are poorly defined. Recently, we identified S100A8/S100A9 (S100A8/A9) alarmins as potential upstream regulators in a chronic equine placentitis model. The current study aimed to determine whether this upregulation is sustained in the acute model and in clinical cases, and to elucidate the expression of their downstream inflammatory mediators. Using an experimental model, we quantified S100A8/A9 mRNA expression in acute (n = 5) and chronic (n = 6) placentitis induced by Streptococcus equi ssp. zooepidemicus. We found mRNA expression of S100A8 and S100A9 was significantly upregulated in chorioallantois during both acute (p < 0.001) and chronic (p < 0.0001) disease compared to controls (n = 5), demonstrating their role is not limited to chronic pathology. A strong positive correlation (r = 0.945) underscored their coordinated expression. Immunohistochemistry revealed minimal staining in controls but dense infiltrations of S100A8/A9-positive neutrophils and macrophages in placentitis tissues. To define the clinical relevance of the downstream pathway, we analyzed RNA sequencing data from clinical placentitis cases (placentitis, n = 4) compared to normal postpartum placenta (control, n = 4). This confirmed upregulation of S100A8/A9 and revealed a concurrent increase in their receptors (TLR4, RAGE) and a spectrum of NF-κB-driven effectors, including pro-inflammatory cytokines (IL1β, IL6, TNF), chemokines (CXCL8, CCL2, CXCL10), and the apoptotic mediator CASP3. Our findings establish that S100A8/A9 upregulation is a sustained feature of equine placentitis and delineates a coherent S100A8/A9-TLR4/RAGE-NF-κB signaling axis that drives inflammation and tissue damage in clinical disease. These findings highlight the diagnostic potential of S100A8/A9 and position this alarmin system as a promising therapeutic target for mitigating infection-induced pregnancy loss. Full article

Allergic conditions have surged to unprecedented levels globally, affecting approximately 30% of the global population. Fungi are among the most significant sources of allergens, accounting for approximately 6% of respiratory issues in the general population. However, identifying the precise cause of respiratory allergies remains challenging. We investigated the potential of two rust species, Tranzschelia pruni-spinosae and Phragmidium rubi-idaei, which infect common fruit plants, to induce inflammatory and asthmatic responses in mouse models of both acute and chronic asthma. Mice were sensitized and administered intranasal challenges with extracts from T. pruni-spinosae and P. rubi-idaei. Levels of pro-inflammatory cytokines (IL-4, IL-5, IL-13, TNF-α, and TGF-β) were measured via ELISA. Additionally, specific IgE production was assessed via ELISA and lung histology was examined using hematoxylin-eosin staining. Both fungal extracts induced significant increases in all tested cytokines, elevated specific IgE levels, and histological changes characteristic of acute and chronic asthma progression in the lungs. The microfungi T. pruni-spinosae and P. rubi-idaei possess strong proinflammatory and asthma-inducing capabilities, suggesting their potential as previously unrecognized fungal allergens. Full article

Phytochemical investigation of the ethyl acetate extract from the aerial parts of Pouzolzia pentandra led to the isolation and identification of fourteen compounds (1–14). These include known compounds such as β-sitosterol (1), bauerenol (2), oleanolic acid (3), 3β-friedelanol (4), kaempferol (5), quercetin (6), 2′,6′-dihydroxy-3′,4′-dimethoxychalcone (7), friedelan-3-one (8), dipterocarpol (9), 3β-hydroxyolean-12-en-28-one 3-p-coumarate (10), daucosterol (11), astilbin (12), 3-methoxy-4-hydroxybenzoic acid (13), and pouzolignan F (14). Among these, compound 14 displayed the most potent inhibitory activity on nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophages, with an IC₅₀ value of 10.54 ± 0.4 µM. Mechanistic studies further revealed that compound 14 significantly suppressed the LPS-induced release of key pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Furthermore, it inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by preventing the nuclear translocation of its p65 subunit. Molecular docking studies were performed to evaluate the anti-inflammatory potential of compound 14 against cyclooxygenase-2 (COX-2) and phosphodiesterase-4 (PDE4). The compound exhibited binding affinities of −6.138 kcal/mol and −9.361 kcal/mol for COX-2 and PDE4, respectively. Subsequent molecular dynamics (MD) simulations confirmed the formation of a stable complex with the active site of PDE4. Collectively, these integrated in vitro and in silico findings demonstrate that pouzolignan F acts as a multi-target anti-inflammatory agent, likely through the inhibition of inflammatory mediators, cytokines, and the NF-κB pathway. Full article

Background/Objectives: Renal cell carcinoma (RCC) is a common and often asymptomatic malignancy with limited treatment options for advanced stages. Chronic inflammation and cellular senescence—collectively termed “inflammaging”—are emerging as key contributors to tumor progression. This study aimed to investigate the expression of inflammaging-related markers in RCC tissues, focusing on the role of PTX3, IL-6, and senescence-associated proteins in the tumor microenvironment. Methods: A retrospective cohort of 57 patients with clear cell RCC who underwent nephrectomy was analyzed. Formalin-fixed paraffin-embedded samples from tumor, peritumoral, and normal renal tissues were examined using confocal immunofluorescence microscopy to assess PTX3, IL-6, p21, and p16 expression. Senescence-associated β-galactosidase staining was performed to identify senescent cells. Serum IL-6 levels were measured by ELISA, and survival analysis was conducted using Kaplan–Meier curves and Cox regression analysis. Results: PTX3 and IL-6 were significantly upregulated in both peritumoral and tumor tissues compared to normal kidney samples (p < 0.001). Expression of senescence markers p21 and p16 were elevated in peritumoral areas (p < 0.001) as compared to normal renal tissues, but their expression was reduced or absent in the tumor core. High-grade and high-stage tumors exhibited stronger PTX3 and IL-6 expression and lower levels of cell cycle inhibitors (p < 0.001). Patients with elevated serum IL-6 levels had significantly lower 5-year cancer-specific survival (p < 0.005) and shorter progression-free survival (p < 0.001). Conclusions: Our findings suggest that peritumoral tissue in RCC exhibits a senescent and proinflammatory phenotype that may support tumor progression. PTX3 and IL-6 are potential biomarkers of disease severity and prognosis. Targeting inflammaging pathways could offer new therapeutic strategies for RCC, particularly in aggressive disease forms. Full article

Conflicting data exist regarding the effect of intradetrusor BoNT/A on the incidence of urinary tract infections (UTIs) in patients with neurogenic detrusor overactivity (NDO), contrary to the increase in UTIs noted in patients with idiopathic OAB. Associations between UTIs, chronic inflammation, and bladder overactivity are acknowledged, albeit not fully understood. Chronic bladder inflammation is common in both NDO and OAB patients, and both animal and human studies suggest a beneficial effect of BoNT/A on both urinary and systemic levels of inflammatory markers. To explore whether intradetrusor BoNT/A injections affect the background for the incidence of UTIs in humans, we investigated in parallel the effect of intradetrusor BoNT/A on the incidence of UTIs and on the urine mRNA levels of urinary pathogen-detecting Toll-like receptors TLR2, TLR4, and TLR5 and of factors acting as intermediates of immune response and promoters of inflammatory reactions (IL1β, IL6, TNFα, and PGE₂). For this purpose, we recruited 22 patients with NDO-associated incontinence who received at least one bladder BoNT/A injection. Urine specimens for the study of UTIs were obtained before the procedure and at routine urodynamic follow-ups at 4–6 weeks, 6 and 12 months post-BoNT/A, and at clinical relapse, while urine specimens for the study of biomarkers were collected at the time of BoNT/A injection and at the abovementioned follow-ups thereafter. Urine specimens from 10 adult healthy volunteers with no OAB symptoms served as the control group in the biomarker study. The genes of interest in the urine were studied by RNA isolation, reverse transcription, and real-time PCR. The urine mRNAs of all biomarkers tested appeared to be upregulated in the patients’ samples compared with the controls, albeit only TLR2 and TLR5 mRNA increases were statistically significant. A progressive downregulation of TLR2, TLR5, IL1β, and IL6 urine mRNAs was noted at one and six months post-BoNT/A. TNFα and PGE₂ mRNAs showed a transient increase at one month post-BoNT/A followed by a dramatic drop at the six months’ follow-up. A similar trend for progressive decline was also noticed in the prevalence of both positive urine cultures and symptomatic UTIs in the same timepoints and additionally at 12 months post-treatment in patients who still benefited from the BoNT/A treatment. Upon clinical relapse, the mRNA levels of PGE₂, IL1β, and IL6 increased in parallel with an increase in the prevalence of UTIs, while the levels of TLRs and TNF-α did not follow the same trend. In summary, intradetrusor BoNT/A injections achieved significant decreases in the urine mRNA levels of pathogen-detecting TLRs, immune response, and inflammation mediator cytokines and PGE₂ in our cohort of patients with NDO-associated incontinence. In parallel, decreases were noted in both the incidence of symptomatic UTIs and rates of positive urine cultures. At the time of clinical relapse, the markers of inflammation and immune response, but not TLRs, were upregulated in parallel with the increased incidence of UTIs, suggesting that the studied genes PGE₂, IL1β, and IL6 could be further explored as potential biomarkers for inflammation/immune response and UTIs in the neurogenic population. Full article

Background: High-intensity interval training (HIT) is a time-efficient strategy to improve metabolic health in children, but its impact on inflammatory markers is still unclear. Therefore, we conducted a meta-analysis to examine the role of HIT on pro-inflammatory cytokines including C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in children with overweight/obesity. Methods: A meta-analysis was conducted following PRISMA guidelines. PubMed, Web of Science, Scopus, and Embase were searched up to 31 July 2025, for studies involving children with overweight/obesity aged 6 to 18 years. Randomized controlled trials and non-randomized controlled trials with outcome measurements that included CRP, IL-6, and TNF-α were included. Random-effects models were used to aggregate a mean effect size (ES) with 95% confidence intervals (CI), and potential moderators were explored. Results: In total, 768 participants from 15 studies were included. HIT significantly improved CRP (574 participants, 13 studies, SMD = −0.63, 95% CI: −1.02 to −0.24, p < 0.01) when compared to control group/pre-intervention. There were no significant effects on IL-6 and TNF-α, and no differences when compared to moderate-intensity training. Subgroup analyses indicated greater effectiveness in intervention duration, work-and-rest ratio, and work time were the significant moderators (p < 0.05). Conclusions: High-intensity interval training is effective for reducing CRP levels in children with obesity. Intervention duration, work-and-rest ratio, and work time can affect the intervention effects of HIT. Full article

Therapeutic strategies that fine-tune epithelial inflammatory responses are highly sought after in respiratory and mucosal disorders, but few molecules selectively target these pathways. Vernoniastrum migeodii (S. Moore) Isawumi (Asteraceae) represents a chemically promising but understudied source of bioactive small molecules. This study aimed to define the metabolite profile of V. migeodii and evaluate the modulation of inflammatory epithelial signaling of the constituents. From the methanolic extract of V. migeodii, five germacranolide sesquiterpenes, vernolide (1), 3′-hydroxylvernolide (2), pectorolide (3), 4′-hydroxypectorolide-14-O-acetate (4) and 4′-hydroxypectorolide (5), together with (6S,9R)-vomifoliol (6), eucarvone (7), luteolin (8), and luteolin-7-O-glucoside (9) were isolated by multiple chromatographic separations. The structures were determined by comprehensive 1D and 2D NMR spectroscopy. Isolated compounds 1 to 9 together with previously reported steroids (10–17) and tripeptide (18) were evaluated in LPS-activated A549 cells by quantitative PCR for interleukin-6 (IL6), interleukin-1β (IL1β), and prostaglandin-endoperoxide synthase 2 (PTGS2) and by enzyme-linked immunosorbent assay (ELISA) for IL-6 and IL-8. Compounds 2, 7, steroids 10–17 and aurantiamide acetate (18) reduced IL6 mRNA relative to the LPS control, while (6S,9R)-vomifoliol (6) increased IL-6 and elevated IL-8. In the assay IL1β and PTGS2 transcripts were not significantly altered. These findings highlight the potential of V. migeodii metabolites as modulators of epithelial inflammatory pathways. Combining chemical and biological evidence provides a clear basis for structure–activity- and pathway-focused studies. Full article

Background/Objectives: Liver cancer is among the most frequent poor-prognosis malignancies worldwide, with currently insufficient effective treatment. The two-stage microwave hyperthermia using magnetic nanoparticles is a modern technique designed to specifically target tumor tissues and facilitate chemotherapy activation, with promising results from fundamental studies across various tumor types. The method consists of a first irradiation, performed before nano-assemblies administration. This is intended to sensitize the tumor by inducing a hyperthermic effect, leading to increasing blood supply, enhancing endothelial damage/permeation and inflammatory activation, with the final goal of improving the diffusion/retention of nano-assemblies in the tumor. Subsequently, the second microwave irradiation follows the injection in the hepatic artery and diffusion in the tumor of the activated nano-assemblies, to further determine a strong, but localized and focalized hyperthermic action. Nano-magnetic assemblies for hyperthermia accomplish the proposed chemo-thermal delivery, i.e., act per se on the tumor and also destabilize co-administered assemblies of nanoparticles loaded with chemotherapeutics, which would be consequently released locally in the most efficient way. This article aims to demonstrate the efficacy of this therapeutic approach in a rat liver model and its potential applicability in patients with liver tumors. Methods: Adult male Wistar rats were used to obtain liver samples, which were divided into three groups, each receiving a different hyperthermia protocol in terms of temperature (41–45 °C), duration, and co-administration of nanoparticles. Results: The most suitable exposure temperature for rat liver appears to be 42 °C, resulting in vacuolar degeneration lesions at the focal level. The effects of thermal conditioning do not appear to be homogeneous in the tested liver, and the controlling environment and methodology should be improved in the near future. The level of hepatic inflammation, as indicated by elevated interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, appears negligible under the current hyperthermia protocol. Conclusions: Two-stage microwave hyperthermia using magnetic nanoparticles is a promising therapeutic modality for liver cancer, with promising results from animal studies opening the way for further research in humans. Full article

In the marine environment, numerous factors endanger the preservation of underwater rock surfaces as well as submerged archeological artifacts, including physical, chemical, and biological processes. Limestone and marble are common materials used in artifacts due to their availability and long-term durability. However, such surfaces provide a suitable substrate for the settlement of micro- and macro-organisms, causing so-called biofouling, which significantly contributes to stone deterioration. Previous studies have demonstrated the applicability of antifouling coatings containing ionic liquids (ILs) on marble surfaces and assessed their durability for up to 15 days under submerged environments. To further corroborate these results, additional physical studies (colorimetric, contact angles, capillarity water absorption measurements, and UV aging) were carried out on treated limestone. Washout tests were also performed on both lithotypes to verify the coatings’ stability under medium-term underwater exposures. The results of these investigations are reported here. Our data confirm that the application of IL-based coatings had no effect on the intrinsic properties of the limestone surfaces, as previously reported for marble, including resistance to daily UV irradiation. In addition, laboratory tests demonstrated good coating durability against seawater erosive action for up to 6 months. Full article

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

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