Search Results (201)

Feed efficiency remains a significant challenge in farmed raccoon dogs, and performance differences can occur even when diets are formulated with similar nutrient levels. Beyond nutrient concentrations, digestion kinetics can alter the timing of carbon and nitrogen availability along the gastrointestinal tract, thereby influencing microbial assembly in a segment-specific way. Twenty 2-month-old male raccoon dogs (Nyctereutes procyonoides) were divided into four dietary groups (n = 5) in a 2 × 2 factorial design. The design combined protein-source formulations containing either soybean cake or dried distillers grains with solubles and starch-source formulations based primarily on either extruded corn or high-amylose corn starch, representing relatively rapid and slow expected digestion characteristics, respectively. The purpose was to assess how digestion-rate synchronization affects jejunal and cecal microbiota structure and whether community state types (CSTs) link diet and feed efficiency. Growth performance varied modestly among treatments, with group B showing the lowest feed-to-gain ratio (F/G) and highest average daily gain (ADG). Starch source significantly affected ADG, while protein and protein × starch interaction influenced F/G. Microbiota profiles were strongly segment-dependent: the cecum had higher richness and diversity than the jejunum. Two-way analyses and Bray–Curtis ordinations showed that the jejunal community was primarily associated with the protein × starch interaction, whereas the cecal community was associated mainly with the protein-source factor and the protein × starch interaction. Network analysis revealed more complex and densely connected microbial communities in the cecum, with core genera occupying central positions. Dirichlet multinomial mixture modeling, performed independently for each intestinal segment, identified two jejunal community states (J-CST1 and J-CST2) and two cecal community states (C-CST1 and C-CST2). J-CST1 and J-CST2 represented alternative lactic acid bacteria-dominated configurations, with J-CST2 enriched in Lactobacillus and J-CST1 characterized by higher abundances of Streptococcus and Bacillus. C-CST2 was represented predominantly by samples from group B and was characterized by higher abundances of Segatella and taxa affiliated with Bacteroidota and Lachnospiraceae. Predicted functional profiles differed between CSTs, involving pathways related to carbohydrate, amino acid, lipid, and bile acid metabolism. Mediation analysis did not provide consistent evidence of significant indirect effects for J-CST membership, whereas C-CST membership was associated with significant estimated indirect effects on final body weight, ADG, and F/G. These findings suggest that dietary protein- and starch-source combinations with different expected digestion characteristics drive segment-specific microbial patterns. Supported by taxonomic, network and functional evidence, cecal CSTs act as an intermediate ecological phenotype that partially explains the variation in growth efficiency, highlighting hindgut community states as potential targets for personalized nutrition of raccoon dogs. Full article

Technology-critical elements are increasingly used in electronics, renewable-energy systems, high-performance alloys and other strategic technologies, yet their occurrence in wild fungi remains poorly characterised. This study evaluated gallium (Ga), germanium (Ge), niobium (Nb), tantalum (Ta) and tungsten (W) in wild mushrooms collected from Leicester and Leicestershire, UK. The dataset was reconstructed at fruiting-body level to avoid pseudo-replication from paired cap and stem records, yielding 121 analytical units. Results were corrected using digestion-date acid blanks, interpreted against analytical-portion-specific working limits of detection and classified as fully quantified (FQ), partially censored (PC) or fully censored (FC). Ga was FQ in 106/121 units and was the only element with sufficient quantitative coverage for continuous distributional estimation; its regression-on-order-statistics median was 475.48 ng g⁻¹ dw (IQR: 278.70–941.63). The corresponding FQ counts were 16 for Ge, 33 for Nb, 10 for Ta and 24 for W, with 7, 4 and 4 additional PC observations for Nb, Ta and W, respectively. In 22 paired Agaricus bitorquis fruiting bodies, Ga concentrations were higher in stems than caps (Wilcoxon p = 5.25 × 10⁻⁵; BH-FDR = 1.05 × 10⁻⁴). Composite topsoils from 26 monitored sites provided park-scale geochemical context only and were not used to infer bioaccumulation or direct soil-to-fungus transfer. These findings establish a blank-corrected and censoring-aware occurrence baseline and suggest exploratory, site-specific potential for wild mushrooms as complementary biomonitoring matrices for selected technology-critical elements, while demonstrating that their usefulness is element-, taxon- and design-dependent. Full article

Obesity is a heterogeneous chronic disease for which safe, scalable adjuncts to lifestyle and clinical care remain needed. Tea derived from Camellia sinensis contains catechins, caffeine, theaflavins, thearubigins, theabrownins, polysaccharides, and other constituents whose abundance is shaped by withering, fixation, partial oxidation, full oxidation, and post-fermentation. This review integrates processing-dependent composition with molecular mechanisms, gut–liver signaling, human evidence, safety, and real-world preparation. Evidence is strongest for modest effects of green-tea catechin–caffeine preparations on energy metabolism and selected anthropometric or lipid outcomes, whereas inhibition of adipogenesis, activation of AMP-activated protein kinase, browning of white adipose tissue, and many appetite-related pathways remain supported mainly by cell and rodent studies. A recent meta-analysis in women with overweight or obesity estimated mean reductions of −1.23 kg in body weight and −3.46 cm in waist circumference, with intervention durations across the included trials typically ranging from 4 to 24 weeks, though most of the evidence derives from short- to medium-term interventions (generally ≤12 weeks); heterogeneity was moderate to high and the average weight effect remained below conventional clinical thresholds. Partially oxidized oolong tea and fully oxidized or post-fermented teas provide distinct profiles of caffeine, oxidized polyphenols, and microbial metabolites; their metabolic effects are promising but are less consistently tested in adequately powered human trials. Across tea types, convergent mechanisms include reduced digestive-enzyme activity, increased fatty-acid oxidation, modulation of thermogenesis, reinforcement of the intestinal barrier, and microbiota-dependent production of short-chain fatty acids and bile-acid signals. Translation is constrained by low systemic polyphenol exposure (i.e., limited bioavailability of intact catechins and their metabolites in circulation due to poor intestinal absorption, extensive phase-II metabolism, and rapid clearance), non-standardized doses and products, short intervention periods, interindividual variability, and limited direct comparisons among tea types. Available clinical data do not support tea as a primary treatment for obesity; rather, unsweetened tea or standardized preparations may serve as adjuncts to evidence-based dietary, physical activity, behavioral, and medical management. Priority areas include physiologically relevant dosing, standardized reporting of brewed-tea composition, long-term trials, and microbiome-informed personalization. Full article

This study examined the effects of replacing 25% (P25) or 50% (P50) of concentrate dry matter (DM) with sun-dried carob (Ceratonia siliqua L.) pods on growth performance, apparent nutrient digestibility, carcass traits, meat quality, serum biochemistry, and rumen microbiology in growing Assaf lambs. Twenty-four weaned male Assaf lambs (initial body weight [BW] 27.0 ± 0.5 kg; 2.5 months of age) were randomly assigned to three dietary treatments (n = 8 per group) in a completely randomized design and fed for 16 weeks. P50 achieved the highest ANCOVA-adjusted least squares mean final BW (53.0 kg) and average daily gain (ADG) (220.8 g/d), followed by P25 (51.1 kg; 203.3 g/d) and the control (46.2 kg; 160.2 g/d) (p < 0.001). Feed conversion ratio (FCR) improved from 8.99 in the control to 6.16 and 6.11 in P25 and P50, respectively, with no significant difference between the two carob-supplemented groups (p < 0.001). Apparent DM and organic matter (OM) digestibility increased with carob inclusion at both 3 and 6 months of age (p ≤ 0.0001). Cold carcass weight (CCW) was higher in carob-supplemented lambs (p < 0.001), whereas carcass muscle proportion did not differ among treatments (p = 0.688), and carcass fat proportion was higher in P25 than in the control (p = 0.039). Warner–Bratzler shear force declined progressively with carob inclusion (p < 0.001), indicating improved meat tenderness. Serum total protein was highest in P25, whereas blood urea nitrogen (BUN), low-density lipoprotein (LDL), and glutamate oxaloacetate transaminase (GOT) decreased with carob inclusion (p < 0.001). Rumen pH was highest in P25 (6.40), total bacterial and lactic acid bacteria (LAB) counts increased, and protozoa counts declined (p < 0.001). Because carob pods replaced concentrate, rather than being added to an isonitrogenous diet, the combined effects of pods per se, reduced crude protein supply, and altered energy density must all be considered when interpreting the results. These findings support carob pods as a practical, locally available partial substitute for concentrate feed in Assaf lamb production under Mediterranean and Near Eastern conditions. Full article

Broiler production keeps intensifying, and the environmental cost of the protein sources that feed it, principally soybean meal and fishmeal, has become harder to justify. Insect meal, derived chiefly from black soldier fly larvae (Hermetia illucens), yellow mealworm (Tenebrio molitor), and housefly larvae (Musca domestica), has emerged as a candidate able to address nutritional, immunological, and ecological goals at once. This review evaluates the evidence on the nutritional composition, digestibility, growth performance, immunomodulatory mechanisms, and gut health effects of insect meal in broiler diets, and weighs these findings against sustainability and economic considerations. The amino acid profile of insect meal is favorable, the fatty acid composition is distinctive, and bioactive compounds, chitin, antimicrobial peptides, and lauric acid among them, shape both innate and adaptive immune responses, reshape the gut microbiota, and reinforce mucosal integrity. Growth performance at partial replacement levels of soybean meal or fishmeal (5–15%) is broadly encouraging, although results differ across insect species, inclusion rate, and processing method. The immunomodulatory pathways involved, Toll-like receptor signaling, cytokine regulation, macrophage polarization, and immunoglobulin synthesis, converge on chitin acting simultaneously as a prebiotic substrate and an immune adjuvant. Critical knowledge gaps persist, including substantial variability in biological outcomes across insect species and rearing substrates, the absence of standardized processing protocols, limited mechanistic data from avian in vivo challenge models, and insufficient long-term validation under commercial production conditions. Cost and regulatory fragmentation across jurisdictions still constrain commercial uptake. Realizing the full potential of insect meal in sustainable broiler production will depend on multi-omics research, precision nutrition tools, and rigorous life-cycle assessment. Full article

Carob-based bigels (BGs) were developed as structured fat replacers and delivery systems for bioactive compounds during gastrointestinal digestion. Four formulations combining different hydrogel (HG)/oleogel (OG) ratios and selective incorporation of two carob extracts—an inositol-rich extract (I-CFE) in the HG phase and a phenolic-rich extract (P-CFE) in the OG phase—were evaluated to determine the influence of microstructure on digestive behavior and bioactive release. Confocal microscopy showed that BG structure was mainly governed by the OG network, while alginate-rich aqueous domains remained dispersed and confined to different extents depending on formulation. This organization strongly influenced hydration, enzyme accessibility and matrix breakdown during digestion. D-Pinitol remained stable throughout gastrointestinal digestion, and its release depended on the accessibility of hydrated aqueous domains. Phenolic release and antioxidant activity were also modulated by matrix architecture and extract localization, with BG-70/30-I+P showing the most efficient and sustained antioxidant response. Lipid digestion and fatty acid bioaccessibility were similarly influenced by BG structure: less compact OG networks promoted greater lipase accessibility and higher bioaccessibility of unsaturated fatty acids, whereas more structured lipid matrices partially restricted lipolysis. Overall, BG functionality was governed primarily by microstructural organization rather than composition alone. Full article

Germinated Andean lupin whole flour (GAL) is rich in protein, dietary fiber, essential amino acids, and bioactive compounds, representing a promising alternative for the development of sustainable plant-based foods. This study investigated the feasibility of partially replacing soy protein isolate (SPI) with GAL in high-moisture extruded meat analogues. A central composite design was applied to evaluate the effects of the GAL ratio (0:100–50:50) and feed moisture content (50–70%) on the technological properties of the extrudates. The Response Surface Methodology was used to model and optimize the process. The incorporation of GAL significantly affected the (p < 0.10) water solubility index (WSI), oil absorption capacity (OAC), cooking loss (CL), yellowness (b*), cohesiveness, and adhesiveness, generating predictive models with satisfactory goodness-of-fit (R² > 0.75). Increasing GAL levels increased the WSI from 6.21 to 18.79% and cooking loss from 1.01 to 3.84%, while reducing OAC from 239.42 to 166.57%, indicating substantial modifications in matrix organization and hydration behavior. Numerical optimization identified an optimal formulation containing 12% GAL, 88% SPI, and 65.5% feed moisture, with a desirability of 77.82%. Model validation showed relative deviations lower than 10% between predicted and experimental values. The optimized meat analogue exhibited high protein content (84.44%), favorable techno-functional properties, and improved nutritional quality, with higher levels of branched-chain amino acids (17.34 g·100 g⁻¹ protein), essential amino acids (33.32 g·100 g⁻¹ protein), and in vitro protein digestibility (90.1%) compared with the control formulation. Multivariate analyses confirmed that phenylalanine, histidine, methionine, and leucine were the main variables that discriminated between the protein sources and the extruded products. Overall, GAL demonstrated strong potential as a sustainable functional ingredient to produce nutritionally enhanced high-moisture meat analogues. Full article

Sustainable agriculture, particularly efficient nitrogen management, is essential for maintaining soil fertility, improving crop quality, and reducing the environmental footprint of agricultural production. This study evaluated the effects of reduced soil-applied nitrogen and foliar application of the nitrogen–sulfur fertilizer Nitron-S on the quality of silage maize (Zea mays L.). A field experiment was conducted using a single-factor design with four fertilization treatments differing in nitrogen supply and foliar fertilization intensity. The silage maize cultivar Farmmortiz was grown under uniform manure application (30 t ha⁻¹) applied in autumn. The control treatment received the full soil-applied nitrogen rate, whereas experimental treatments received 50% of the conventional nitrogen dose supplemented with foliar Nitron-S at doses of 20, 40, and 60 dm³ ha^-1, applied twice during the growing season. After harvest, plant yield and selected quality parameters were determined, including dry matter, crude protein, sugars, starch, ash, neutral detergent fiber (NDF), acid detergent lignin (ADL), ammonia fraction, and organic matter digestibility (VOS). Fertilization treatments significantly affected most quality traits. The highest Nitron-S rate increased starch concentration (up to approximately 30% under N4) but also elevated ADL content (by about 25%) and slightly reduced VOS (only by about 1–3%. Partial replacement of soil-applied nitrogen with foliar nitrogen–sulfur fertilization improved the nutritional quality of maize silage and reduced nitrogen input. This approach may contribute to more sustainable maize production. Full article

The search for sustainable alternatives to fish oil (FO) in aquafeeds is imperative for the long-term sustainability of aquaculture. This study evaluated the effects of partially replacing FO with oils derived from Hermetia illucens (RH) and Musca domestica (RY) larvae at 10%, 30%, and 50% levels on growth, lipid metabolism, hepatic antioxidant capacity, and gut microbiota in juvenile Cyprinus carpio. Results showed distinct source- and dose-dependent responses. RY produced a consistent dose-dependent trend in growth parameters, whereas RH exhibited a biphasic pattern, with growth impairment at 30% replacement and recovery at 50%. Both oils significantly suppressed hepatic fatty acid synthase (FAS) activity, yet this suppression was accompanied by dose-dependent up-regulation of fas expression, particularly at high RH and RY levels, indicating complex post-transcriptional regulation. RH at higher replacement levels reduced digestive enzyme activities and antioxidant capacity, while higher RY caused minimal disruption. Both oils reshaped gut microbiota toward oil-specific community structures. Two-way ANOVA revealed significant synergistic interactions between oil source and replacement level for most serum biochemical and hepatic antioxidant parameters (ηp² > 0.90). These findings demonstrate that RY is a tolerable alternative across a wide replacement range, though all RY groups exhibited lower growth than the control, 30% is identified as the maximum tolerable level; whereas RH requires precise dosing at 10% to avoid the 30% impairment threshold. Full article

Long-term storage can impair the feeding value of corn. This study evaluated whether dietary Laminaria japonica polysaccharide (LJP) could alleviate the adverse effects of aged corn in Hu sheep. Twenty-one male Hu sheep (39.05 ± 3.55 kg) were assigned to a normal-corn diet (NC), an aged-corn diet (AC), or the AC diet supplemented with 0.5% LJP (AC+LJP; n = 7) for 70 d, including a 14-d adaptation period. Compared with NC, AC reduced average daily gain, gain-to-feed ratio, the apparent digestibility of crude protein, neutral detergent fiber and acid detergent fiber, ruminal total volatile fatty acids, acetate and butyrate, and muscle glutathione peroxidase activity. LJP supplementation restored average daily gain, gain-to-feed ratio, and crude protein and neutral detergent fiber digestibility to levels comparable with NC. It also increased ruminal ammonia nitrogen, microbial crude protein, total volatile fatty acids, acetate, butyrate, and isobutyrate relative to AC, while reducing muscle malondialdehyde concentration and increasing total antioxidant capacity. Dietary treatment had little effect on carcass traits, most meat-quality variables, or overall rumen bacterial diversity. In conclusion, supplementation with 0.5% LJP partially alleviated the decline in nutrient utilization and rumen fermentation associated with aged corn and improved muscle antioxidant status. These findings support the potential use of LJP as a functional feed additive to improve the utilization of aged-corn-based diets in sheep. Full article

The narrow-clawed crayfish (Pontastacus leptodactylus), a non-native species accidentally introduced into China’s Irtysh River Basin, has formed a wild population with aquaculture potential, but its natural diet and protein utilization remain poorly understood. This study investigated its feeding ecology and digestive responses to protein sources to support ecological assessment and feed formulation. Intestinal contents and muscle samples from wild crayfish were analyzed using eDNA metabarcoding and fatty acid signature analysis. In vitro digestibility of 10 protein ingredients was evaluated with crude digestive enzyme extracts, and a 4-week trial compared an all-plant-protein diet (PPD) with an all-animal-protein diet (APD). eDNA indicated an omnivorous diet dominated by planktonic taxa, especially Rotifera, and fatty acid biomarkers suggested contributions from diatoms, dinoflagellates, phytoplankton, zooplankton, and benthic organisms. Soybean meal and soy protein concentrate showed high dry matter digestibility, whereas fishmeal and krill meal had high crude protein digestibility and amino acid release. Compared with PPD, APD increased feed intake, apparent nutrient digestibility, hemolymph nutritional indicators, villus height, and intestinal trypsin and lipase activities; however, intestinal integrity was preserved in both groups, and most intestinal antioxidant indices did not differ significantly. These findings indicate that animal proteins enhance nutrient utilization in P. leptodactylus, while selected plant proteins may serve as partial alternatives. Full article

This study was designed to assess the protective efficacy of dihydromyricetin (DHM) against intestinal injury in Chinese soft-shelled turtles (Pelodiscus sinensis) caused by partial replacement of fishmeal (FM) with fermented rapeseed meal (FRM), and to uncover the molecular mechanisms involved. Turtles were fed an FM-based control diet, an FRM-substituted diet, or FRM diets supplemented with DHM at 0.5‰ (DHMT1), 1.0‰ (DHMT2) or 2.0‰ (DHMT3) for 8 weeks. Growth performance, digestive enzyme activities, antioxidant parameters, inflammatory cytokines, and intestinal histomorphology were assessed, and intestinal transcriptomics and metabolomics were also performed. FRM replacement significantly improved growth performance; however, this beneficial effect was accompanied by notable intestinal mucosal oxidative damage, as evidenced by decreased villus height, increased lumen space, and lamina propria edema, along with elevated pro-inflammatory cytokines (IL-1β and TNF-α) and MDA content, alongside reduced GSH and CAT activities. DHM supplementation dose-dependently ameliorated these adverse effects by restoring mucosal integrity, digestive enzyme activities, redox homeostasis, and inflammatory balance, ultimately improving growth performance. Transcriptomic KEGG analysis revealed that DHM enriched pathways related to glycerophospholipid metabolism, glutathione metabolism, drug metabolis-cytochrome P450, and polyunsaturated fatty acid metabolism. Metabolomics further confirmed dose-dependent remodeling of phospholipids and bile acids. Integrated omics demonstrated that DHM likely regulates detoxification, anti-inflammatory, membrane repair, and antioxidant pathways. In conclusion, DHM demonstrates a protective effect against FRM-induced intestinal mucosal oxidative damage in P. sinensis, which may be mediated by a synergistic combination of enhanced detoxification, anti-inflammatory modulation, restoration of phospholipid membrane integrity, and reinforcement of antioxidant defenses. Full article

The common products of acidogenesis, the key stage in the process of anaerobic digestion, are lactate, butyrate, propionate, and acetate. They were decomposed in the Up-flow Anaerobic Sludge Blanket bioreactors working in continuous-flow open systems. A comprehensive analysis of variations in both isotopic ratios and concentrations of organic acids in the effluents was conducted to enhance comprehension of methanogenic processes. The analysis of carbon isotope fractionation in the CO₂-CH₄ system, as evidenced by the α¹³C_CO2-CH4 factor, has indicated that acetate decarboxylation has occurred. Furthermore, a decline in CO₂ levels was observed, accompanied by the predominance of butyrate and propionate, despite the presence of acetic acid in the effluents from all the bioreactors. Butyric acid demonstrated the greatest resistance to decomposition, resulting in ¹³C-enrichment of DIC. Lactic acid was utilised almost entirely. The observations presented above were subsequently validated through statistical analysis. A comparative analysis of the δ¹³C(CH₄) and δ¹³C(CO₂) values of our study with those of other natural substrates (detritic lignite, xylite, maize silage, and cattle manure) was undertaken, and it was found that isotope fractionation differs significantly in closed (potential thermodynamic processes) and open systems (expected Rayleigh processes). In the context of open systems, the isotope fractionation factor α¹³C_CO2-CH4 during methaneogenesis has been observed to attain values that are consistent with those observed in CH₄ oxidation. The study revealed that the presence of acetate in the substrate (i.e., the M4 bioreactor) led to the generation of CO₂ with a higher proportion of light carbon isotopes. This, in turn, resulted in a shift in the isotope fractionation factor (i.e., α¹³C_CO2-CH4) to values below 1.03. Our results suggest that methanogenic pathway signatures in open, continuous-flow systems may only be partially apparent. This is because substrate depletion drives Rayleigh-type isotope enrichment, while the dominance of a single substrate and its constant inflow stabilise pathway expression and shift control towards substrate dynamics rather than intrinsic microbial changes. Our finding suggests that isotope-based diagnostics could enhance process control in biogas plants by identifying substrate-driven limitations and facilitating more efficient and stable CH₄ production. Full article

The aim of this study was to evaluate the effect of adding white mulberry (Morus alba L.) fruit to extruded corn snacks on their polyphenol profile, antioxidant properties, acetylcholinesterase (AChE) inhibitory activity and the preservation of phenolic compounds in an in vitro digestion model. Mixtures of corn grits with 0, 10, 15 and 20% dried mulberry fruit were extruded at temperatures of 100, 120 and 140 °C, and then the total polyphenol content (TPC) and antioxidant activity (IC₅₀ for DPPH) were determined. For selected samples (0%, 140—3E; 15% mulberry, 140—9E; mulberry—13E), further antioxidant tests (FRAP, CUPRAC, Fe²⁺ chelation) were performed, the phenolic compound profile (UHPLC) and AChE inhibition were assessed, and a two-step in vitro digestion was conducted. The addition of mulberry significantly increased TPC- and free-radical-scavenging capacity compared to the control sample, with snacks containing 15% mulberry extruded at 140 °C showing approximately a 3.5-fold higher TPC than the control, while dried mulberry fruit itself exhibited about a five-fold higher TPC than this enriched snack. Among the snacks, the most favorable DPPH-radical-scavenging effect was obtained for the variant with 20% mulberry at 120 °C (IC₅₀ = 0.176 mg/mL), whereas the mulberry fruit extract reached an IC₅₀ of 0.0926 mg/mL. In a two-step in vitro digestion model, the mulberry-enriched snack with 15% fruit retained 69.3% of its initial TPC after the gastric phase and 33.3% after the intestinal phase, compared with 55.0% and 20.0%, respectively, for the control snack, confirming a partial but meaningful preservation of phenolic compounds under simulated gastrointestinal conditions. UHPLC analysis confirmed that mulberry and the enriched snacks are a rich source of chlorogenic acids and their isomers, as well as quercetin and kaempferol glycosides, which largely survived the two-step in vitro digestion, despite an observed decrease in TPC after the gastric stage and a further reduction after the intestinal stage. At the same time, mulberry extract and mulberry-enriched snacks exhibited high antioxidant activity in all tests conducted and in vitro AChE inhibitory activity, suggesting that Morus alba L. fruit has the potential to be used as a natural functional ingredient in the production of gluten-free snacks with antioxidant and potentially neuroprotective properties. Full article

Pomegranate (Punica granatum), a shrub belonging to the Lythraceae family, has long been recognized for its diverse pharmacological benefits, including potential roles in managing inflammation and diabetes. The present study explored the insulin-secretory and β-cell proliferative properties of the ethanol extract of P. granatum fruit peel (EEPG) and assessed its influence on glucose regulation in high-fat-fed diet-induced obese mice (HFDi-OM) through in vivo and in silico studies. In vitro, EEPG was found to activate cAMP-dependent pathways and regulate K_ATP channels, thereby enhancing glucose-stimulated insulin secretion from BRIN-BD11 β-cells, with partial reliance on extracellular calcium. EEPG promoted β-cell proliferation, as indicated by an increase in Ki-67 positive cells, and displayed inhibitory effects on glucose diffusion and starch hydrolysis, suggesting a capacity to delay carbohydrate digestion and absorption. Furthermore, EEPG demonstrated antioxidant activity by neutralizing free radicals. In an acute test, EEPG (at doses of 150 and 250 mg/5 mL/kg) improved oral glucose tolerance and elevated plasma insulin levels. Long-term oral treatment for 21 days to HFDi-OM led to a significant reduction in fasting blood glucose, body weight, and food and fluid intake. It also enhanced gastrointestinal motility and improved lipid profiles by increasing HDL and lowering total cholesterol, LDL, and triglycerides. The therapeutic properties of EEPG are likely attributed to its rich bioactive components, including flavonoids (quercetin, kaempferol, catechin, and epicatechin) and phenolic acids (ellagic acid), which exhibited strong multi-target binding affinities in in silico molecular docking studies toward SUR1, PDE4, PI3K, and α-amylase, thereby supporting enhanced insulin secretion, β-cell function and glucose homeostasis. Full article