This study investigated the effects of Lactiplantibacillus plantarum ATG-K2 supplementation on body composition in adults with overweight and obesity. In this 12-week, randomized, double-blind, placebo-controlled trial, 80 participants were randomized to receive ATG-K2 or placebo. In the per-protocol analysis (ATG-K2: n = 32; placebo: n = 35), ATG-K2 significantly reduced total body fat mass and body fat percentage compared with placebo (p = 0.0206 and p = 0.0260, respectively). Lean mass was preserved, and the lean-to-fat ratio was higher in the ATG-K2 group, although the between-group difference was not statistically significant (p = 0.0653). Hip circumference showed a significant between-group difference (p = 0.0493). No significant differences were observed in abdominal fat area or obesity-related biomarkers, and no serious adverse events were observed. These findings support ATG-K2 supplementation as a safe and effective nutritional strategy for reducing body fat while preserving lean mass in adults with overweight and obesity.
Research on marine functional foods is shifting from their use as sources of isolated bioactive compounds toward engineered food systems that combine sustainable processing, targeted gastrointestinal delivery, and precision-nutrition approaches. This review discusses how diverse marine biological resources, including macroalgae, marine animals, and marine microorganisms, together with valorized side streams from seafood processing, can be transformed into standardized functional ingredients through green extraction, biorefinery, fermentation, membrane technologies, and food-grade delivery systems. These engineering strategies can enhance ingredient stability, bioaccessibility, and controlled release, thereby providing a technological basis for investigating microbiome-mediated pathways relevant to the gut–kidney axis. For example, fucoidan-rich marine polysaccharide fractions may act as microbiota-accessible substrates, with processing-dependent structural characteristics potentially influencing microbial fermentation, short-chain fatty acid production, intestinal barrier regulation, and downstream inflammatory pathways relevant to renal homeostasis. Evidence from marine ingredients and broader microbiome research suggests potential effects on intestinal barrier integrity, short-chain fatty acid production, and gut-derived metabolites associated with renal stress; however, direct clinical evidence demonstrating gut–kidney-axis modulation by engineered marine functional foods remains limited. Finally, we highlight how multi-omics, artificial intelligence, and precision nutrition can support individualized formulation design and biomarker-guided interventions. Integrating sustainable food engineering with microbiome science provides a translational framework for developing next-generation marine functional foods for metabolic and kidney health. Together, this framework positions marine functional foods not as uniformly beneficial health products, but as source-specific and deliberately engineered food systems whose biological effects depend on composition, processing, delivery, and host context.
Arginase dysregulation is implicated in various pathological conditions, including cardiovascular diseases, erectile dysfunction, and cancer, making it an attractive therapeutic target. In this study, enzymatic hydrolysates of white lupin (Lupinus albus) and blue lupin (Lupinus angustifolius) protein isolates were evaluated for arginase-inhibitory activity. Among the hydrolysates tested, white lupin flavourzyme hydrolysate exhibited the highest inhibitory potency (∼35% at 800 μg/mL), followed by trypsin and pepsin hydrolysates, while alcalase hydrolysates showed no activity. Reverse-phase HPLC fractionation followed by tandem mass spectrometry identified ten peptide sequences from the most active fractions. Two structurally distinct peptides, the short hydrophobic hexapeptide DMGAVA and the long polycationic 16-mer VVALKKVGVLKKPGPT, demonstrated the highest arginase inhibition and were selected for mechanistic studies. Lineweaver-Burk analysis revealed mixed-type inhibition kinetics with distinct profiles: DMGAVA substantially affected both Km and Vmax (Ki ∼266 μM), whereas VVALKKVGVLKKPGPT showed predominantly competitive behavior with minimal change in Vmax (Ki ∼589 μM).
Ambient particulate matter (PM) disrupts alveolar epithelial integrity by inducing oxidative stress and inflammatory signaling. While Sargassum horneri has been reported to protect against PM-associated airway injury, whether its sterol-enriched fraction contributes to glucocorticoid receptor (GR)-associated epithelial regulation has not been investigated. Here, we show that a sterol-enriched Sargassum horneri ethanol extract (S-SHE) contained the highest level of fucosterol among the solvent-partitioned fractions and attenuated PM-induced cytotoxicity. In PM-exposed MLE-12 cells, S-SHE reduced intracellular ROS generation, malondialdehyde levels, and surface accumulation of Al and Fe, and alleviated PM-induced morphological alterations. S-SHE also suppressed TLR2/MyD88/TRAF6-associated inflammatory signaling, NF-κB transcriptional activity, and the expression of pro-inflammatory cytokines and chemokines. Notably, S-SHE restored GR expression and modulated surfactant-related gene expression, including Sftpb and Sftpc. These results suggest that sterol-enriched components of Sargassum horneri attenuate PM-induced epithelial stress and may have potential relevance to corticosteroid-related epithelial regulation.
Cellular senescence is a core hallmark of aging and a major risk factor for most chronic diseases. Natural products targeting senescent cells have garnered increasing attention for anti-senescence potential in aging-related disease intervention. Previous studies revealed that hydrolyzed chicken extract (HCE) exerts neuroprotective effects, but its role in senescent cell clearance and underlying mechanisms remains unclear. Here, we investigated the anti-senescent effects and mechanisms of HCE in D-galactose-induced senescent HT-22 hippocampal neurons, compared with the traditional essence of chicken (EC). HCE significantly enhanced cellular antioxidant capacity, reduced SA-β-gal positivity, restored cell cycle progression, inhibited senescence-associated secretory phenotype (SASP) secretion, and promoted autophagic flux, with a slightly stronger efficacy than EC. We further identified cyclo (Val-Pro), cyclo (His-Pro), and cyclo(Gly-Pro) as bioactive components, with cyclo(His-Pro) showing the strongest potency. Mechanistically, HCE and these cyclopeptides exerted effects via SIRT1/AMPK/mTOR-mediated autophagy, which was fully abolished by SIRT1 knockdown or targeted pathway inhibition.
As a major citrus flavonoid, hesperidin (HP) shows bone-protective potential, yet its role in calcium–phosphorus homeostasis and antioxidant mechanisms remains unclear. This study investigated the anti-osteoporotic effects of HP in retinoic acid (RA)-induced osteoporotic mice and primary bone marrow mesenchymal stem cells (BMSCs). HP promoted BMSC proliferation, migration, and osteogenic differentiation, with increased alkaline phosphatase (ALP) activity and mineralization. Network pharmacology identified antioxidant PI3K/AKT/FOXO1 pathways as key targets, with fibroblast growth factor 23 (FGF23) as a pivotal effector. In osteoporotic mice, HP normalized serum calcium, phosphorus, and 25-hydroxyvitamin D, increased bone formation and decreased resorption markers, alleviating bone loss and preserving trabecular microarchitecture and enhancing biomechanical properties. Mechanistically, PI3K/AKT/FOXO1-mediated FGF23 suppression was essential for osteoprotection, as confirmed using a PI3K inhibitor. Collectively, these findings suggest that HP ameliorates RA-induced osteoporosis by restoring calcium–phosphorus homeostasis via PI3K/AKT/FOXO1-dependent FGF23 inhibition, underscoring its potential as a functional food ingredient.
Sweet tea (Rubus suavissimus S. Lee) is a natural plant characterized by its low caloric content, high sweetness, and health-promoting properties, with polysaccharides being its primary active components. The sweet tea polysaccharides (STP), identified as an acidic heteropolysaccharide, demonstrated excellent anti-inflammatory potential in vitro by reducing NO, TNF-α, and IL-6 secretion and increasing IL-10 secretion in LPS-stimulated RAW264.7 cells. This study aimed to investigate the protective effects of STP and its underlying mechanism in mice with ulcerative colitis (UC). The results showed that STP ameliorated clinical symptoms in UC mice, including weight loss, disease activity index (DAI) scores, and pathological damage. Furthermore, STP bidirectionally modulated the secretion of key inflammatory factors (TNF-α, IL-6, IL-10) in both the colon and liver through the gut-liver axis. Additionally, STP enhanced the expression of tight junction proteins (ZO-1, Claudin-3, and Occludin) in the colonic epithelium, thereby repairing the impaired intestinal barrier and reducing endotoxin translocation. 16S rRNA sequencing analysis revealed that STP intervention enhanced gut microbiota diversity, increased the abundance of beneficial bacteria, and suppressed the growth of pathogenic bacteria. This microbial restructuring led to an increased production of short-chain fatty acids (SCFAs), which further contributed to the maintenance of intestinal microenvironment homeostasis and immune regulation. Our findings elucidate the synergistic role of STP in exerting anti-inflammatory effects and regulating gut microecology via the gut–liver axis, providing novel insights into natural product-based intervention strategies for UC and highlighting its promising application prospects as a functional food or therapeutic agent.
Obesity and its associated metabolic diseases have become a global public health issue. However, the long-term application of existing therapeutic drugs for obesity is limited due to their side effects. Huai Chrysanthemum is a medicinal and edible chrysanthemum cultivar from Jiaozuo, China, and is known to contain bioactive polysaccharides. In this study, we used water extraction and ethanol precipitation to prepare Huai Chrysanthemum polysaccharides (CPs). C57BL/6J mice were randomly divided into a normal group, a high-fat diet model group, and a CPs intervention group (treated with 200 or 400 mg/kg of CPs by oral gavage for 12 weeks). We analyzed metabolic indicators, inflammatory factors, the gut microbiota, and short-chain fatty acids. Analysis revealed that CPs intervention for 12 weeks significantly inhibited weight gain, reduced fat accumulation, improved insulin resistance and dyslipidemia, alleviated hepatic steatosis, and reduced systemic inflammation levels. Phenotypic observations revealed that CPs intervention was accompanied by restoration of intestinal barrier injury, modulation of gut microbiota structure (decreased Bacillota/Bacteroidota (B/B) ratio, reduced abundance of pro-inflammatory genera), and elevated production of short-chain fatty acids (SCFAs) in obese mice. Collectively, these data indicate that CPs exert significant anti-obesity activities and can improve metabolic disorders, and the concurrent improvements in intestinal barrier integrity, microbial composition, and SCFAs metabolism may be closely associated with the metabolic benefits of CPs. Our findings provide scientific evidence for the use of CPs as a functional food ingredient to prevent diet-induced obesity.
Intestinal health is critical for efficient swine production, yet effective intervention strategies remain limited. This study evaluated the impacts of dietary Brevibacillus laterosporus BL1 (live or heat-killed form) on finishing pigs, focusing on serum parameters, antioxidant capacity, intestinal barrier, cecal microbiota, and microbial metabolic profiles. Results demonstrated that relative to the control group (CON), B. laterosporus BL1 (both live and heat-killed forms) decreased serum pro-inflammatory cytokines, ameliorated serum lipids, and enhanced systemic antioxidant capacity. Moreover, the heat-killed form was comparable to the live bacteria in strengthening the intestinal barrier, as evidenced by improved intestinal morphology, upregulated barrier-related proteins (ZO-1, Muc-1, and Muc-2), decreased serum lipopolysaccharide levels, and raised intestinal anti-inflammatory cytokines (IL-10 and IL-22) and immunoglobulins (IgG and IgM). Further, metagenomic analysis of cecal digesta demonstrated that heat-killed B. laterosporus BL1 elevated the proportions of potentially beneficial genera Limosilactobacillus and Lactobacillus, while suppressed potential pathogens Clostridium and Terrisporobacter. Consistently, heat-killed B. laterosporus BL1 increased cecal levels of lactate, total short-chain fatty acids (SCFAs), acetic acid, and butyric acid, while decreasing the concentration of phenol, indole, skatole, and biogenic amines (total amines, methylamine, cadaverine, and putrescine). Thus, heat-killed B. laterosporus BL1 emerges as a promising agent for promoting overall physiological status and intestinal health in finishing pigs.
Fibromyalgia is difficult to treat and often cause widespread musculoskeletal pain, leading to depression. We used intermittent cold stress to induce chronic pain and depression comorbidity (CPDC) in mice. CPDC mice exhibited chronic mechanical and thermal hyperalgesia, accompanied by depressive symptoms. Metabolomics results showed that eicosapentaenoic acid (EPA) has anti-inflammatory effects. Western blotting results revealed decreased programed cell death protein 1 (PD-1) receptor in the cerebellum of CPDC mice. However, there was significantly increased neuroinflammation due to higher protein levels in astrocyte and microglia, as well as their neurotransmitters high mobility group box 1, S100 calcium binding protein B, and toll-like receptor 4 receptor signaling. EPA administration can prevent CPDC by increasing PD-1 expression and inhibiting inflammation-related pathways. Similar results were also observed in transient receptor potential vanilloid 1 knockout mice. In conclusion, long-term oral EPA administration can prevent CPDC by increasing PD-1 in the cerebellum and inhibiting neuroinflammatory pathways.
Myrciaria cauliflora (jaboticaba) is widely recognized for its polyphenol-rich fruit; however, its seeds are typically discarded and remain largely underexplored despite their potential bioactive value. This study investigated the effects of different extraction conditions on the phytochemical composition and bioactivity of jaboticaba seed extracts. The optimized extract exhibited potent bioactivity, characterized by high phenolic content and strong antioxidant capacity. It effectively scavenged free radicals and inhibited lipid peroxidation, while reducing reactive oxygen species (ROS) and nitric oxide (NO) production in macrophages. These antioxidant and anti-inflammatory effects were further reflected in improved survival and enhanced redox status in Drosophila melanogaster. Moreover, in an MPTP-induced Parkinson's disease mouse model, the extract attenuated oxidative stress and improved motor performance. Collectively, these findings demonstrate that jaboticaba seed extract possesses antioxidant, anti-inflammatory, and neuroprotective properties, highlighting its potential as a functional food ingredient.
Tartary buckwheat leaf is a promising sustainable source of rhamnogalacturonan-I-rich pectic polysaccharides (TBP) with marked in vitro immunostimulatory activity. However, their in vivo efficacy and structure-activity relationships remain unknown. Here, we investigated TBP fractions differing in esterification degree, molecular mass, and branching in a murine immunosuppression model. All TBP fractions attenuated immunosuppression, an effect associated with modulating gut microbial homeostasis, enhancing levels of short-chain fatty acids (SCFAs), reinforcing gut barrier integrity, and improving systemic immune markers. Structural modifications augmented bioactivity; low-esterified TBP-D and low-molecular-mass, low-branching TBP-F outperformed native TBP. TBP-F had the strongest effects, significantly improving immune organ indices, cytokines, immunoglobulins, SCFAs, and tight-junction proteins. Microbiota analysis revealed that all TBPs enriched Muribaculaceae and decreased dysbiosis-associated taxa, with TBP-F most strongly suppressing detrimental bacteria. These results imply that TBPs with lower molecular mass, less branching, or reduced esterification possess superior immunostimulatory potency, supporting their development as immune-enhancing functional foods.
Obesity is a chronic, complex disease closely linked to the gut microbiota and lipid metabolism. Hawthorn, a fruit with functional nutritional value, is known to aid digestion and relieve food stagnation; however, the mechanisms by which it combats obesity remain unclear. This study established a mouse model of obesity using a high-fat diet (HFD) to investigate the functional effects of cold-brewed hawthorn juice (HAW). Key assessments included body weight gain, glucose and energy metabolism, lipid homeostasis, hepatic lipid deposition, gut microbiota diversity, and the effects of fecal microbiota transplantation (FMT). The results showed that HAW intervention significantly reduced HFD-induced weight gain and fat mass percentage; improved glucose tolerance and insulin sensitivity; increased oxygen consumption and thermogenesis; alleviated lipid metabolism disorders; inhibited lipogenesis while enhancing lipid oxidation in adipose and liver tissues; and promoted thermogenesis in brown adipose tissue and inguinal white adipose tissue. Furthermore, 16S rDNA and metabolomic analyses indicated that HAW markedly reduced the Firmicutes/Bacteroidetes (F/B) ratio in the gut microbiota and modulated serum metabolites, including (+)-lariciresinol, Bavachin, Ponicidin, and 4-Hydroxycordoin, thereby mitigating the onset and progression of obesity. Subsequent FMT analysis confirmed HAW's remarkable functional role in ameliorating HFD-induced obesity by modulating the abundance of Acetatifactor, Odoribacter, and Alistipes. In summary, HAW inhibits adipose tissue hypertrophy and improves hepatic lipid dysregulation by regulating the gut microbiota and lipid metabolism, thereby effectively ameliorating HFD-induced obesity in mice. These findings provide systematic scientific insights into daily functional fruit dietary interventions and health management for people with obesity.
Type 2 diabetes mellitus (T2DM) is closely associated with male reproductive dysfunction, but effective functional food-derived interventions remain limited. Polygonatum sibiricum polysaccharide (PSP), a major bioactive constituent of the medicinal and edible plant Polygonatum sibiricum Redouté, has metabolic regulatory potential. This study evaluated PSP in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM mice. PSP was extracted from geo-authentic Polygonatum sibiricum Redouté collected from the Wudang region of Hubei Province, China, and characterized by SEC-MALLS-RI, HPAEC, and FT-IR. PSP was identified as a high-polysaccharide-content acidic heteropolysaccharide with a broad molecular weight distribution, a weight-average molecular weight of 39.194 kDa and a monosaccharide profile dominated by glucose, galactose, and galacturonic acid. After 5 weeks of oral administration at 400, 800, or 1600 mg kg−1 d−1, PSP altered fasting blood glucose trajectories and tended to improve body weight maintenance. PSP also improved testicular histoarchitecture and sperm quality, accompanied by increased steroidogenesis-related and blood-testis barrier-associated tight junction protein expression. Group-level sperm malformation decreased from 49.3% in model mice to 35.8% and 25.4% in the medium- and high-dose groups, respectively. PSP treatment was associated with reduced ROS-associated fluorescence, attenuated NF-κB-related signaling, and lower Tnf, Il1b, and Il6 mRNA expression. Overall, PSP may alleviate T2DM-associated testicular dysfunction in association with improved systemic metabolic status and favorable changes in the local testicular microenvironment. These findings support PSP as a potential multi-target functional food-derived candidate for diabetes-associated male reproductive injury, although further studies are required to clarify its direct targets and causal mechanisms.
Burdock root (Arctium lappa L.) is rich in dietary fiber and polyphenols with hypoglycemic potential, but its application in low-glycemic index (GI) staple foods is underexplored. This study developed burdock root extract-enriched buckwheat noodles (B-BRE) for type 2 diabetes mellitus (T2DM) management. The optimal 3.6% burdock root extract-enriched buckwheat noodles (B-BRE2) had a low estimated GI, increased resistant starch, and strong α-amylase and α-glucosidase inhibition. In a high-fat diet and streptozotocin induced T2DM mice, B-BRE2 significantly reduced fasting blood glucose, improved glucose tolerance, alleviated insulin resistance, mitigated organ injury, restored gut microbiota diversity, and enriched beneficial Lactobacillus. B-BRE2 ameliorates T2DM via modulating starch digestibility and gut microbiota, offering a novel strategy for low-GI functional staples.
Human milk oligosaccharides (HMOs) modulate gut microbiota and intestinal barrier integrity; however, age-dependent microbiota-mediated effects remain insufficiently defined. This study employed a controlled in vitro “microbe-host interaction” model to evaluate direct and fermentation-mediated effects of 2′-fucosyllactose (2’-FL) and 3-fucosyllactose (3-FL) on epithelial barrier function. Infant and adult microbiota were encapsulated and co-cultured with T84 epithelial cells, while barrier resistance and gene expression related to glycocalyx and tight junctions (TJs) were quantified under basal and disruption conditions. 3-FL exerted superior direct protective effects, enhancing glycocalyx-associated gene expression and mitigating barrier impairment. Microbial metabolism differed by age. Infant microbiota produced primarily one of short-chain fatty acids (SCFAs) acetate, lactate, and succinate whereas adult microbiota generated SCFAs, particularly butyrate. Butyrate improved barrier resistance and modulated glycocalyx integrity. These findings demonstrate structure-dependent HMOs activity and age-specific microbial metabolic responses, highlighting mechanistic links between microbial fermentation and epithelial barrier regulation.
Our previous studies have shown that Lycium barbarum polysaccharide (LBP) alleviates rheumatoid arthritis (RA) symptoms in gut microbiota-dependent manner, with the key bacterium and the underlying mechanism remain unidentified. In this study, LBP was fermented in vitro by Romboutsia lituseburensis, Lactobacillus johnsonii, or a combination of both strains, and were administered to pseudo-germ-free RA rats. Only R. lituseburensis-fermented LBP significantly alleviated RA and markedly enriched osteoclast differentiation pathway-related genes. Twenty-six metabolites produced by R. lituseburensis, including glutamic acid-proline-glutamine (EPQ), that reduced inflammation and inhibited osteoclast differentiation by downregulating Rankl expression and its downstream factors. Notably, EPQ was also proposed to bind RANKL and potentially interfere with the RANKL/RANK pathway, thereby suppressing the expression of osteoclastogenesis-related genes. These findings identify R. lituseburensis as the key bacterium mediating the anti-RA effects of LBP, with its fermentation products, particularly EPQ, serving as critical active substances that inhibit inflammation and modulate osteoclast differentiation via the RANKL-RANK signaling.
This study aimed to investigate the transformation of Polygonatum cyrtonema Hua (PCH) by lactic acid bacteria (LAB), including Lactobacillus plantarum (P-5, Z-2, and 28–1) and Lactobacillus pentosus P-7. LAB-fermented PCH (FPCH) altered sugar and acid profiles, along with increasing total phenolics, flavonoids, and saponins. FPCH developed a more complex and pleasant aroma profile, marked by increased key flavor compounds such as 2-undecanone and β-damascenone; meanwhile, astringency and green/herbal off-odors, represented by epigallocatechin (EGCG), were reduced. LAB fermentation increased naringin and 4-hydroxybenzoic acid contents, enhancing antioxidant capacity. Notably, FPCH fermented by L. plantarum P-5 (P-5-FPCH) protected PC12 cells against oxidative stress and further alleviated uric acid-induced oxidative injury in HK-2 renal tubular epithelial cells. In hyperuricemic mice, P-5-FPCH reduced serum uric acid levels and alleviated renal injury, likely by increasing caffeic and cinnamic acids. Transcriptome analysis of LAB revealed the above-mentioned related genes (sacA, pyk, and adh). Overall, LAB fermentation offers a safe and promising bioprocessing strategy to enhance the quality and bioavailability of PCH.
Objective We aimed to investigate the therapeutic effects of Moringa oleifera leaf polysaccharide (MOLP) in ulcerative colitis (UC) and the underlying mechanism involving macrophages polarization. Methods Dextran sodium sulfate (DSS)-induced colitis mouse model, as well as lipopolysaccharide (LPS) and interferon-γ (IFN-γ) stimulated macrophages (PMA-differentiated THP-1 cells) were used for investigations. Therapeutic effect of MOLP was evaluated by measuring disease activity index (DAI), myeloperoxidase (MPO) activity and histological morphology in mice, with 5-aminosalicylic acid as positive control. Macrophages were determined by flow cytometry and immunofluorescence staining. Glycolysis activity was determined by measuring lactic acid content, extracellular acidification rate (ECAR) and the uptake of fluorescent deoxyglucose analog 2-NBDG. Results MOLP effectively alleviated colitis symptoms of DSS-induced UC mice, as demonstrated by reduced DAI score and MPO activity, alleviation of colon shortening, and mitigated colonic histopathological damage. Besides, MOLP decreased the proportion of M1 macrophages and the mRNA expression of their specific factors (TNF-α, IL-1β and iNOS), while increasing M2 macrophages and their specific factors (CD206, Arg1 and Chil3). Based on LPS and IFNγ-stimulated macrophages, MOLP treatment suppressed M1 macrophages polarization by inhibiting the glycolysis activity, which was confirmed by the glycolysis inhibitor 2-DG. Mechanistically, HMGB1 was down-regulated by MOLP, and recombinant HMGB1 protein treatment could offset the curative effects of MOLP on UC. Furthermore, HMGB1 interacted with HAVCR2, and the latter mediated macrophage glycolysis by PI3K/Akt/HIF-1α pathway, thereby regulating M1 macrophages polarization. Conclusion MOLP could alleviate UC by regulating macrophages M1 polarization through HMGB1/HAVCR2 mediated glycolysis.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by selenium depletion, disrupted redox balance and hyperactivated NLRP3 inflammasome. Conventional clinical agents fail to synchronously modulate selenium metabolism and inflammatory signaling cascades. In this work, tea polysaccharide-stabilized selenium nanoparticles (TPS-SeNPs) were synthesized and comprehensively characterized. TPS-SeNPs fabricated using 2 mg/mL tea polysaccharide exhibited uniform spherical morphology with an average diameter of ∼39 nm, favorable dispersibility and excellent low-temperature storage stability. Biosafety evaluation in Kunming mice demonstrated no detectable hepatic or renal toxicity. In vitro experiments on LPS-stimulated Raw264.7 macrophages revealed that TPS-SeNPs directly suppress cellular inflammatory activation. Further in vivo assays on DSS-induced C57/BL6J colitis mice indicated that oral TPS-SeNP administration markedly alleviated weight loss, colon shortening and intestinal mucosal damage, reduced disease activity and histological scores, downregulated pro-inflammatory cytokines and MDA, while upregulating anti-inflammatory IL-10 and antioxidant SOD. DSS induction triggered systemic selenium loss across visceral tissues, which could be efficiently replenished by TPS-SeNPs, with the most prominent selenium accumulation observed in colonic tissue. Selenium-deficient HepG2 cell models confirmed that TPS-SeNPs upregulate the activities of GPx and TrxR selenoenzymes in both dose- and time-dependent manners, thereby mitigating oxidative stress and inhibiting the NLRP3/Caspase-1/IL-1β signaling pathway. In contrast, sulfasalazine only partially attenuates intestinal lesions without rectifying selenium deficiency or restraining NLRP3 inflammasome. Collectively, TPS-SeNPs exert therapeutic effects against UC via the core regulatory cascade: selenium homeostasis–selenoenzymes–oxidative stress–NLRP3 inflammasome. This study provides experimental evidence supporting TPS-SeNPs as a safe nutritional adjuvant for UC intervention.
