Search Results (419)

Given the limitations of clinical and potent natural α-glucosidase inhibitors, novel selective inhibitors are urgently needed. To accelerate discovery, we employed machine learning-integrated virtual screening to rapidly evaluate a library of 100 K⁺ compounds, identifying a series of selective α-glucosidase inhibitors. Activity validation demonstrated that these inhibitors exhibit significantly enhanced selectivity and potency compared to the positive control acarbose. Mechanistic studies through inhibition kinetics and fluorescence quenching revealed their improved inhibitory profile. Molecular docking indicates that key interactions—hydrogen bonding or salt bridges with the catalytic residue ASP526—strengthen binding within the active site. These interactions competitively obstruct enzyme-substrate binding, thereby amplifying inhibition. In vitro and in vivo starch digestion assays further corroborated these findings. Full article

The early developmental transition from endogenous to exogenous feeding is a critical period in carnivorous fish larvae, often associated with high mortality rates in aquaculture. Although trypsin, a key protease in protein digestion, is hypothesized to play a pivotal role in initiating exogenous feeding, the expression dynamics and functional contributions of trypsin and isoforms during early development remain poorly characterized in carnivorous species. This study explores the critical role of trypsin in the early feeding process of carnivorous fish, using mandarin fish (Siniperca chuatsi) as a model, which is a commercially valuable species that faces significant challenges during this phase due to its strict dependence on live prey and underdeveloped digestive system. Phylogenetic analysis indicates that, compared to herbivorous and omnivorous fish, carnivorous fish have evolved a greater number of trypsins, with a distinct branch specifically dedicated to try. RNA-seq data revealed the expression profiles of 13 trypsins during the early developmental stages of the mandarin fish. Most trypsins began to be expressed in large quantities with the appearance of the pancreas, reaching a peak prior to feeding. In situ hybridization revealed the spatiotemporal expression pattern of trypsins, starting from the pancreas in early development and later extending to the intestines. Furthermore, inhibition of trypsins activity successfully suppressed early oral feeding in mandarin fish, which was achieved by increasing the expression of cholecystokinin 2 (CCK2) and proopiomelanocortin (POMC) to suppress appetite. These findings enhance our understanding of the adaptive relationship between the ontogeny of the digestive enzyme system and feeding behavior in carnivorous fish. This research may help alleviate bottleneck issues in aquaculture production by improving the survival rate and growth performance of carnivorous fish during critical early life stages. Full article

An 8-week feeding trial was conducted to evaluate the potential of dietary soy isoflavones (SIF) to counteract growth inhibition, oxidative stress, endoplasmic reticulum stress, and inflammation induced by oxidized fish oil in Monopterus albus (initial body weight: 26.0 g). The fish were reared in outdoor pond-based net cages (2.0 m × 1.5 m × 1.5 m; 3 cages per treatment, 50 fish per cage) and fed five isonitrogenous and isolipidic experimental diets: a control diet (CON) containing 2.2% fresh fish oil, and oxidized fish oil diets (2.2% oxidized oil) supplemented with 0 (SIF0), 25 (SIF25), 50 (SIF50), or 100 (SIF100) mg/kg SIF. The fish were fed to satiation daily at 4:00 pm at a rate of 3–5% of initial body weight. Compared with the CON group, the SIF0 group showed significantly reduced growth performance, with a final weight gain rate of 84.13%, and decreased intestinal digestive enzyme activity. Hepatic superoxide dismutase (SOD) and catalase (CAT) activities declined to 1.78 U/mgprot and 4.13 U/mgprot, respectively, while serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels increased to 24.95 U/L and 37.56 U/L. The SIF0 diet also up-regulated the expression of hepatic endoplasmic reticulum stress-related genes (perk, ire1, atf6) and pro-inflammatory genes (tnfα, il-1β). Dietary SIF supplementation alleviated these adverse effects, with the most pronounced improvements observed at 50 mg/kg SIF based on overall performance. These results demonstrate that SIF can serve as a functional feed additive to mitigate oxidative stress and related metabolic disorders in M. albus. Full article

The tree bean (Parkia timoriana), an underutilized legume valued for its nutritional profile, represents a potential source of bioactive peptides for diabetes management. To our knowledge, this is the first study to identify and characterize DPP-IV inhibitory peptides derived from tree bean seed protein hydrolysates. The tree bean proteins were digested with trypsin, thermolysin, chymotrypsin, pepsin, and simulated gastrointestinal (SGI) enzymes, among which SGI hydrolysis yielded the highest degree of hydrolysis (14%) and strongest DPP-IV inhibitory activity (IC₅₀ = 1289 ± 58 µg/mL). Guided by DPP-IV inhibitory assays, sequential fractionation using strong cation exchange and RP-HPLC yielded the most potent fraction, H5, with an IC₅₀ of 949 ± 50 µg/mL. After peptide identification and synthesis, APLGPF (AF6) emerged as the most potent inhibitor, with an IC₅₀ of 396 ± 18 µM. Enzyme kinetics revealed a non-competitive inhibition mechanism, corroborated by molecular docking, which indicated binding at an allosteric site of DPP-IV. Furthermore, AF6 remained stable under simulated gastrointestinal digestion and enzymatic exposure, highlighting its resistance to proteolysis. Taken together, these findings highlight P. timoriana as an underexplored source of peptides with DPP-IV inhibitory activity and identify AF6 as a promising lead for developing functional foods or nutraceuticals aimed at type 2 diabetes management. Full article

Bacillus species represent promising alternatives to antimicrobial growth promoters, offering potential benefits for productivity and gut health in broilers. This study aimed to isolate Bacillus strains with inhibitory activity against Clostridium perfringens and evaluate their probiotic potential through in vitro and in vivo approaches. In Experiment 1 (in vitro), five strains—B. siamensis C66, B. tequilensis Y7, B. velezensis L15, B. amyloliquefaciens C271, and B. siamensis C377—were isolated and assessed for stress tolerance, digestive enzyme production, and antimicrobial activity. All strains demonstrated high survival rates under acid and bile stress, produced multiple digestive enzymes, and significantly inhibited the growth of C. perfringens. In Experiment 2 (in vivo), 630 day-old male Arbor Acres broilers were randomly assigned to one of seven dietary treatments for 42 days: a negative control (CON, basal diet), a positive control (ANfT, basal diet supplemented with 6.4 g/t virginiamycin), and five groups receiving basal diet supplemented with one of the Bacillus strains at 1 × 10¹¹ CFU/kg. Among these, B. amyloliquefaciens C271 significantly increased breast muscle yield (p < 0.05), improved jejunal morphology—evidenced by increased villus height and villus height-to-crypt depth ratio (p < 0.05)—and positively modulated cecal microbiota composition compared to the CON group. These findings demonstrate that the newly isolated B. amyloliquefaciens C271 possesses strong probiotic properties in vitro and promotes growth performance and gut health in broilers, suggesting its viability as an antibiotic growth promoter substitute. Full article

There is increasing interest in the health-promoting potential of plant protein-derived peptides for managing metabolic disorders. This study investigated the impact of pepsin digestion on pre-hydrolysed versus non-hydrolysed pea protein. Pepsin digestion resulted in a higher degree of hydrolysis in pre-hydrolysed samples (64%) compared to the non-hydrolysed samples (~40%). The pepsin hydrolysates from the pre-hydrolysed protein showed stronger inhibition of key metabolic enzymes compared to non-hydrolysed samples. After ultrafiltration to enrich peptides <10 kDa, inhibition of α-amylase, α-glucosidase, and ACE was markedly enhanced, achieving a maximum of 44.5%, 54% and 95%, respectively. Peptidomic analysis identified unique peptide sequences in the ultrafiltered pre-hydrolysed fraction, in silico prediction confirmed their bioactive potential. These findings demonstrate enhanced bioactivity in pre-hydrolysed pea protein samples following pepsin hydrolysis, which was most evident in the ultrafiltrated fractions. Overall, this approach highlights the relevance of enzymatic hydrolysis and peptide enrichment strategies in developing functional ingredients to support glucose regulation and cardiovascular health. Full article

The sea cucumber (Apostichopus japonicus) is highly susceptible to environmental stress during aquaculture, storage, and transportation, often resulting in autolysis and considerable economic losses. UVA irradiation and Vibrio splendidus infection were used to induce skin ulceration in A. japonicus. In this study, UVA irradiation and V. splendidus infection were used to induce skin ulceration, and the effectiveness of a compound inhibitor in delaying its onset was evaluated. The degree of skin ulceration in A. japonicus was evaluated. Body wall tissues were collected to measure the activities of self-digesting enzymes, AchE, cathepsin L, SOD, and CAT. Caspase-3 expression was also analyzed to assess apoptosis and tissue damage. The results indicated that soaking A. japonicus in the inhibitor composition significantly delayed the onset of skin ulceration. After 72 h of UVA irradiation, the skin ulceration in group Eg was 0.55%, which was significantly lower than that in groups Cg and Wg. In the V. splendidus infection model, group Eg showed a 4-day delay in the onset of skin ulceration, compared to group Cg. Enzyme activity and gene expression analysis revealed that the inhibitor composition significantly reduced self-digesting enzyme expression in the A. japonicus body wall, increased SOD and CAT activities, and inhibited Caspase-3 expression. This study provides valuable theoretical insights into controlling skin ulceration in A. japonicus during aquaculture, preservation, and transportation. Full article

Infusions of the leaves of Ribes magellanicum (Grossulariaceae) are used as a digestive in southernmost South America. This work aimed to assess the composition and activity of infusions and MeOH:H₂O 7:3 extracts of R. magellanicum leaves on enzymes related to metabolic syndrome (α-glucosidase, α-amylase, and pancreatic lipase), as well as their antioxidant capacity. Samples from a longitudinal gradient from central southern Chile to the islands in the Beagle Channel were investigated. Lyophilized infusions and extracts were used for all determinations, including inhibition of the selected enzymes, total phenolic (TP), total flavonoid (TF), total procyanidins (TPC), and antioxidant capacity (DPPH, FRAP, TEAC, and ORAC). The composition of the samples was assessed by HPLC-DAD. Some 99 compounds were tentatively identified by HPLC-MSⁿ. The main phenolics were quantified using calibration curves with reference compounds. Relevant differences exist in the ratio of constituents in infusions compared to hydroalcoholic extracts. The samples were inactive towards α-amylase and pancreatic lipase at 100 and 50 µg/mL, respectively. Assay-guided isolation of α-glucosidase inhibitors led to fractions with high activity (IC₅₀: 0.02–0.05 µg/mL). The strong inhibition of α-glucosidase and antioxidant capacity of the infusion and extracts of R. magellanicum leaves support its traditional use in southern Patagonia. Full article

Diabetes mellitus is a characteristic metabolic disorder with diverse complications. α-Amylase and α-glucosidase, as key digestive enzymes regulating blood glucose, are important targets for diabetes prevention and management through their inhibition. This study investigated the inhibitory effects of six porphyrin compounds (TAPP, TCPP, THPP, Cu–TCPP, Fe–TCPP, Ni–TCPP) on two enzymes through in vitro inhibition assays, spectroscopic experiments, and molecular docking techniques. All six compounds effectively inhibited the activities of both enzymes. For α-amylase, the inhibitory potency (IC₅₀ = 13.03–245.04 μg/mL) followed the order TAPP > THPP > TCPP > Fe–TCPP > Ni–TCPP > Cu–TCPP. All six compounds exhibited more potent inhibitory activity against α-glucosidase (IC₅₀ = 0.24–25.43 μg/mL), with potency in the order of THPP > Ni–TCPP > Fe–TCPP > TCPP > Cu–TCPP > TAPP. Fluorescence quenching experiments revealed that all compounds statically quenched the intrinsic fluorescence of both enzymes (with Fe–TCPP exhibiting static-dominant mixed quenching against α-amylase), indicating complex formation. These interactions significantly altered the enzymes’ conformations, the microenvironments of Tyr/Trp residues, and secondary structure content, consequently reducing their catalytic activity. By examining the inhibitory impact of porphyrin compounds on α-amylase and α-glucosidase, this research establishes a vital experimental and theoretical basis for diabetes therapeutics. Full article

Metabolic illnesses such as obesity, type 2 diabetes and hyperuricemia are becoming more common, driving intensified research into nutritional interventions through targeted dietary modifications as a primary preventive strategy. The apparent fluctuation in blood glucose value is modulated by the digestive behavior of starch. Moreover, polyphenols—historically considered to be anti-nutrients due to their inhibition of digestive enzymes and sometimes astringent taste—can be used to significantly improve the functional properties of starch. This can be achieved primarily through α-amylase inhibition and the modulation of other enzyme activities, alongside the antioxidant and anti-inflammatory effects of polyphenols. Depending on their fine structure, starches are digested at different rates: rapidly digestible starch (RDS) spikes blood glucose; slowly digestible starch (SDS) smooths postprandial blood glucose peaks; resistant starch (RS) feeds gut microbes. The fine structure of starches, such as straight-chain starches, can form complexes with polyphenols through their ‘empty V-type’ structures under controlled processing conditions. Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and in vitro digestion modeling analyses have revealed that the formation of starch–polyphenol complexes primarily occurs due to certain interactions (hydrophobic interactions and hydrogen bonding) which lead to stabilized structures, including V-type encapsulation; this significantly increases the content of RSs and slows down enzymatic digestion rates. These complexes lower the GI values of foods via molecular barrier effects, while synergistically boosting antioxidant and anti-inflammatory activities; their anti-digestive capabilities were found to be superior even to those of ordinary starch–lipid compounds. However, limitations persist in the research and application of starch–polyphenol complexes: human bioavailability validation; incomplete mechanistic understanding of multicomponent interactions; industrial scalability challenges due to polyphenol instability. Full article

Large-fruited cranberry (Vaccinium macrocarpon Ait.) is a rich source of polyphenolic compounds, including anthocyanins, flavonols, and unique A-type proanthocyanidins, which exhibit strong antioxidant and health-promoting properties. Cranberry pomace, a by-product generated during juice and concentrate production, remains underutilized despite being abundant in dietary fiber and non-extractable polyphenols (NEPPs). In this study, cranberry pomace was characterized phytochemically and applied as a functional ingredient in biscuits at levels of 5%, 10%, and 15% substitution of wheat flour. Total polyphenol content (TPC) and antioxidant activity (ABTS^•+, DPPH^•) were significantly higher in pomace compared to whole fruit values reported in the literature, which can be attributed to the concentration of polymeric proanthocyanidins and flavonols in skins and seeds. Biscuits enriched with pomace exhibited a dose-dependent increase in TPC and antioxidant capacity, with the 15% variant showing up to 6-fold higher polyphenol content and over 30-fold higher ABTS^•+ activity after in vitro digestion compared to control. Digestion also released NEPP bound to the fiber matrix, improving bioaccessibility. Moreover, extracts from digested biscuits reduced oxidative stress in Saccharomyces cerevisiae and inhibited COX-1, COX-2, and AChE activities, suggesting potential anti-inflammatory and neuroprotective effects. These findings highlight cranberry pomace as a sustainable, high-value ingredient for functional foods, aligning with circular economy strategies. Full article

Objectives: Alpinia japonica (A. japonica) is traditionally used for digestive disorders, but its hypolipidemic mechanisms remain unclear. This study investigated the lipid-lowering effects of its fruit (SJGS), rhizome (SJGJ), and leaf (SJY) extracts, exploring their bioactive constituents and organ-specific mechanisms. Methods: Sprague Dawley rats (n = 8/group) fed a high-fat diet received SJGS, SJGJ, or SJY (200 mg/kg/day) for 4 weeks. Serum lipids (TC, TG), liver enzymes (AST, ALT), and intestinal barrier markers (DAO) were measured. Gut microbiota (16S rDNA sequencing), hepatic histopathology, and ileal tight junction proteins were analyzed. Transcriptomics and qPCR assessed ileal gene expression. LC-MS identified chemical constituents, while network pharmacology predicted compound-target interactions. Results: All extracts significantly reduced serum TC (↓ 27–33%), TG (↓ 29–38%), AST/ALT (↓ 22–30%), and DAO (↓ 35–42%) versus controls (p < 0.05). They improved hepatic steatosis, enhanced intestinal barrier function, and modulated gut microbiota (↑ α-diversity, ↓ Firmicutes/Bacteroidetes ratio). Transcriptomics revealed PPAR signaling as the core pathway: SJGS/SJGJ downregulated fatty acid oxidation genes (ACSL1, ACOX1, ACADM), while SJY upregulated APOA1 (2.3-fold). LC-MS identified 33–48 compounds/part, with seven shared constituents. Network analysis prioritized three flavonoids (pinocembrin, luteolin, galangin) targeting TNF, AKT1, and PPAR pathways. Conclusions: The findings suggest A. japonica extracts ameliorate hyperlipidemia through distinct mechanisms—SJGS/SJGJ may inhibit fatty acid oxidation, while SJY potentially enhances APOA1-mediated clearance. Shared flavonoids likely contribute to these effects via PPAR signaling, supporting its traditional use. This study provides a scientific basis for the sustainable utilization of A. japonica resources. Full article

Background: Dietary polyphenols, particularly flavonoids, have been associated with improved glycemic control and reduced risk of type 2 diabetes. Raspberry leaf (RL) is a rich but underexplored source of such bioactives, including ellagitannins, flavonoids, and phenolic acids. While raspberry fruit has received some attention in nutritional science, the metabolic effects of raspberry leaf—especially its influence on postprandial glucose and insulin responses—remain largely unstudied. Objective: This study is the first to investigate the acute effects of RL tea consumption on postprandial blood glucose and insulin levels in healthy individuals following intake of common dietary carbohydrates (sucrose and glucose). Methods: In a randomized crossover study, 22 healthy adults (12 males, 10 females) consumed 50 g of glucose or sucrose with or without 10 g of RL tea in four separate sessions. Blood glucose and insulin levels were measured at fasting and at 15, 30, 60, 90, and 120 min post-ingestion. A total of 37 polyphenolic compounds were identified in the RL infusion using LC–MS, following a 5-minute hot water extraction. The contents of ellagitannins, flavonoids, and phenolic acids were 38 mg, 7 mg, and 4 mg per 10 g of RL, respectively, contributing to a total polyphenol content of 50 mg per 10 g. Results: When RL tea was consumed with sucrose, postprandial blood glucose levels were significantly reduced at 15 and 30 min by 1.19 ± 0.88 mmol/L (25.59% reduction, p = 0.001) and 2.03 ± 1.05 mmol/L (43.57% reduction, p = 0.0004), respectively. Insulin concentrations were also significantly lower at 15 min (113.90 ± 59.58 pmol/L, p = 0.019), 30 min (161.76 ± 91.96 pmol/L, p = 0.0008), and 60 min (139.44 ± 75.96 pmol/L, p = 0.025). No significant differences were observed with glucose ingestion. Conclusions: This study provides the first clinical evidence that RL tea can blunt early postprandial glycemic and insulinemic responses to sucrose in healthy individuals. The data suggest that these effects are likely mediated by relatively low levels of polyphenols—particularly ellagic acid—through inhibition of carbohydrate-digesting enzymes such as α-glucosidase and β-fructofuranosidase. These findings support the potential of RL tea as a simple, dietary approach to modulate glucose metabolism and warrant further investigation in populations at risk for metabolic disorders. Full article

Background/Objectives: Diabetes mellitus (DM) is one of the most common metabolic disorders, with a continually increasing population incidence. One of the main therapeutic approaches for this condition involves the inhibition of alpha-amylase and alpha-glucosidase—key enzymes involved in carbohydrate breakdown. Silver nanoparticles have exhibited inhibitory activity against both enzymes, suggesting their potential in regulating postprandial blood glucose levels. This study aimed to evaluate the antidiabetic potential of silver nanoparticles biosynthesized with Stenocereus queretaroensis flower extract. Methods: The flower extract was prepared and, following a qualitative and quantitative phytochemical analysis, was utilized in the reaction to biosynthesize S. queretaroensis flower extract nanoparticles (SAgNPs). The SAgNPs were characterized using UV–visible spectroscopy, dynamic light scattering (DLS), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction (XRD), and Fourier transform infrared spectrophotometry (FTIR). The antidiabetic potential of the biosynthesized SAgNPs was evaluated in vitro using alpha-amylase and alpha-glucosidase inhibitory assays, while an animal model was used for postprandial hypoglycemic activity in healthy mice. Results: The phytochemical analyses showed the presence of phenolic compounds and flavonoids like sinapic acid, p-coumaroyl tyrosine, procyanidin dimer β1, and dihydroquercetin in the flower extract. The SAgNPs were found to be rough and spherical in shape, with an average size of 99.5 nm. The inhibition of alpha-amylase and alpha-glucosidase by SAgNPs exhibited an IC₅₀ of 4.92 µg/mL and 0.68 µg/mL, respectively. The animal model results suggested that SAgNPs at 100 mg/kg caused a significant decrease in the postprandial glucose level; this effect is likely attributable to delayed carbohydrate digestion, as supported by the in vitro findings. Conclusions: S. queretaroensis-synthesized silver nanoparticles may constitute a promising option for antidiabetic therapy. Full article

Chlorophyll, the green pigment essential for photosynthesis, abundantly found in green vegetables and algae, has attracted growing scientific interest for its potential therapeutic effects, particularly in diabetes management. Recent research highlighted that chlorophyll and its derivatives may beneficially influence glucose metabolism and oxidative stress, key factors in diabetes. This review examines current knowledge on how chlorophyll compounds could aid diabetes control. Chlorophyll and its derivatives appear to support glucose regulation primarily through actions in the gastrointestinal tract. They modulate gut microbiota, improve glucose tolerance, reduce inflammation, and alleviate obesity-related markers. While chlorophyll itself does not directly inhibit digestive enzymes like α-glucosidase, its derivatives such as pheophorbide a, pheophytin a, and pyropheophytin a may slow carbohydrate digestion, acting as α-amylase and α-glucosidase inhibitors, reducing postprandial glucose spikes. Additionally, chlorophyll enhances resistant starch content, further controlling glucose absorption. Beyond digestion, chlorophyll derivatives show promise in inhibiting glycation processes, improving insulin sensitivity through nuclear receptor modulation, and lowering oxidative stress. However, some compounds pose risks due to photosensitizing effects and toxicity, warranting careful consideration. Chlorophyllin, a stable semi-synthetic derivative, also shows potential in improving glucose and lipid metabolism. Notably, pheophorbide a demonstrates insulin-mimetic activity by stimulating glucose uptake via glucose transporters, offering a novel therapeutic avenue. Overall, the antioxidant, anti-inflammatory, and insulin-mimicking properties of chlorophyll derivatives suggest a multifaceted approach to diabetes management. While promising, these findings require further clinical validation to establish effective therapeutic applications. Full article