Search Results (334)

Immune-mediated inflammatory diseases (IMIDs) arise from interactions among genetic susceptibility, epithelial barrier function, microbiota, diet, and other environmental exposures. Modern diets influence mucosal immunity not only through fibre intake, food processing, and microbiota composition, but also through a less explored exposure layer: plant-derived molecules with potential immune activity. Crop breeding, intensive agriculture, global trade, gluten-free substitutes, and plant-based food technologies have changed the spectrum, dose, concentration, and matrix in which plant defence proteins, antinutritional factors, endogenous toxicants, and novel plant antigens reach the intestinal surface. In this structured, hypothesis-generating narrative review, we propose dietary adjuvanticity as a mechanistic framework for considering how selected food-derived molecules may amplify mucosal immune responsiveness, modify antigen presentation, disturb barrier function, or lower tolerance thresholds without necessarily acting as classical autoantigens. The framework differs from general food-derived immunomodulation, nutritional exposomics, and diet-microbiota-host interaction models by focusing specifically on adjuvant-like immune amplification at the intestinal mucosa. The ASIA concept is used only in Shoenfeld’s functional sense, as an analogy for exogenous immune amplification through innate activation, danger signalling, bystander activation, epitope spreading, and loss of tolerance in susceptible hosts; it is not applied as a dietary diagnosis. Wheat amylase-trypsin inhibitors, gluten epitopes, lectins, potato glycoalkaloids, saponins, quinoa prolamins, emerging legume proteins, L-canavanine, and tolerance-promoting plant substrates are discussed with explicit separation of established clinical evidence, strong mechanistic evidence, preclinical/ex vivo evidence, and speculative disease-modifier hypotheses. Overall, plant-derived exposures are best interpreted as potential modifiers within the IMID exposome, not as primary causes of autoimmunity. Testing this model will require defined exposures, food-matrix and processing studies, biomarkers of barrier and immune activation, patient stratification, and controlled human studies. Full article

Background: Polygodial (9), a drimane sesquiterpene dialdehyde from Drimys winteri, has not previously been examined against carbohydrate-hydrolyzing enzymes. Methods: Regioselective Wittig olefination at C12 gave the enoate 10; reduction of the remaining C11 aldehyde with NaBH₄ was followed by spontaneous intramolecular conjugate addition, affording the annellated tetrahydrofuran 12a and the bridged ether 12b. Results: All three derivatives inhibited α-glucosidase and α-amylase more strongly than the parent compound. Compound 12a was the most active α-glucosidase inhibitor (IC₅₀ = 53.98 ± 3.0 µM, against 90.36 ± 4.0 µM for acarbose) and, in docking, the only derivative to occupy the acarbose-binding site of the enzyme (−8.1 kcal/mol). However, this 12a–α-glucosidase pose was not maintained during the 200 ns simulations. The enoate 10 was the most active α-amylase inhibitor (IC₅₀ = 42.32 ± 2.1 µM, against 78.24 ± 3.9 µM for acarbose; −8.5 kcal/mol). Over 200 ns of molecular dynamics, the 10–α-amylase complex remained associated, with binding attributed by MM-GBSA mainly to van der Waals and lipophilic terms. Conclusions: Converting the dialdehyde into an enoate or a cyclic ether increases carbohydrase inhibition and determines which of the two enzymes is preferentially inhibited. Full article

Backgroud: The growing prevalence of diabetes mellitus necessitates the development of safe and effective inhibitors of carbohydrate-metabolizing enzymes, particularly α-amylase and α-glucosidase. Methods: In this study, a series of pyrimidine–oxadiazole derivatives (1–10) was synthesized and structurally characterized using elemental analysis, HREI-MS, and ¹H/¹³C NMR spectroscopy. The compounds were evaluated for in vitro inhibitory activity against both enzymes, with acarbose as the reference drug. Results: IC₅₀ values ranged from 6.70 ± 0.20 to 21.10 ± 0.10 μM for α-amylase and 7.10 ± 0.20 to 21.80 ± 0.40 μM for α-glucosidase. Compounds 2, 3, and 6 displayed superior dual inhibitory activity compared to acarbose (IC₅₀ = 10.10 ± 0.20 and 10.50 ± 0.10 μM, respectively). Structure–activity relationship analysis revealed that electronic effects of aromatic substitutions significantly influenced enzyme inhibition. Molecular docking supported the experimental findings by demonstrating stable binding interactions within the enzyme active sites. Preliminary safety profiling in male Wistar rats showed no observable behavioral changes, hematological abnormalities, or hepatic and renal dysfunction following repeated administration of the lead compound. Conclusions: These results highlight pyrimidine–oxadiazole derivatives as promising and well-tolerated dual enzyme inhibitors for further antidiabetic drug development. Full article

Microbial α-amylases are widely used in industrial biotechnology due to their catalytic efficiency, stability, and cost-effective production. Identifying sources of newly isolated bacterial strains with desirable biochemical properties remains important for improving industrial enzyme applications. In this study, a newly isolated strain, Bacillus simplex BCHCNZ282B, isolated from soil samples collected in Ergani (Diyarbakır, Turkey), was investigated for its extracellular α-amylase production. The enzyme production conditions were optimized, followed by purification involving ammonium sulfate precipitation, dialysis, and final purification by starch-affinity chromatography. The purified enzyme was biochemically characterized in terms of optimal activity conditions; stability; kinetic parameters; and the effects of metal ions, inhibitors, and detergents. Optimal α-amylase production was obtained at 35 °C and pH 7.0 after 36 h of incubation. The optimum activity of the purified enzyme was attained at 50 °C and pH 7.0. Sequential purification resulted in a six-fold increase in specific activity and a final recovery yield of 19%. The enzyme’s molecular mass was 70 kDa. Increased enzyme activity was obtained in the presence of Mg²⁺ and Mn²⁺, while EDTA was inhibitory to enzyme activity. The purified enzyme maintained high relative activity from pHs 7.0 to 9.0 and was active at all temperatures studied. In addition, enzyme activity was observed even in the presence of some of the tested detergents. The α-amylase produced by B. simplex BCHCNZ282B possessed many biochemical properties, such as stability in a wide range of pH values, high-temperature activity, and resistance to several detergents, which indicate many potential biotechnological applications of the enzyme. Nevertheless, further research on genomic characterization and structural analysis should be conducted to establish the industrial application of the enzyme. Full article

Luteolin and its derivative glycosides (cynaroside, orientin and isoorientin) are compounds with a flavonoid structure of plant origin. There are different studies in the literature on the antioxidant capacities of the structures and their inhibition effects on some enzymes. In this study, the antioxidant capacities of each structure were determined comparatively, and their inhibitory effects against enzymes associated with different diseases such as acetylcholinesterase, butyrylcholinesterase, α-glycosidase and α-amylase were evaluated by comparative investigation in vitro and in silico. Antioxidant capacities were determined for each structure by iron ions (Fe³⁺), cupric ions (Cu²⁺), Fe³⁺−Triphenyltetrazolium chloride (TPTZ) reduction methods and 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), N,N-dimethyl-p-phenylenediamine (DMPD) radical scavenging methods. According to the results obtained, it was determined that the antioxidant capacities of the structures were close to or better than butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), trolox, α tocopherol and ascorbic acid, which are used as standard antioxidants. The results of the study, which was conducted to determine the inhibition effects of the structures on the determined enzymes, were found to coincide experimentally and theoretically. According to the inhibition results, the best inhibitors were found as orientin (IC₅₀: 27.729 nM) for the human carbonic anhydrase I (hCA I), cynaroside (IC₅₀: 18.24 nM) for the human carbonic anhydrase I (hCA II), isoorientin (IC₅₀: 1.93 nM) for the acetylcholinesterase (AChE), and cynaroside (IC₅₀: 6.41 and 7.15 nM) for the butyrylcholinesterase (BChE) and α-glycosidase enzymes. Additionally, absorption, distribution, metabolism, and excretion (ADME) profiles and toxicity assessments of the structures were determined in a virtual environment. Full article

Background/Objectives: Diabetes mellitus (DM) is a critical metabolic condition with escalated blood glucose levels caused by insulin resistance, restricted insulin production, and the activity of alpha-amylase and alpha-glucosidase enzymes. Methods: This current work focuses on the synthesis and evaluation of novel Pyrimidine-derived pyrazole-based thiadiazole derivatives to target DM by inhibiting α-amylase and α-glucosidase. Results: The findings exhibited that, except for three compounds, all other synthesized derivatives inhibited α-amylase and α-glucosidase enzymes with IC₅₀ values ranging from 5.17 μM to 29.84 μM on α-amylase and 7.60 μM to 31.62 μM on α-glucosidase, in comparison to the standard drug Acarbose (α-amylase IC₅₀ = 8.25 ± 0.80 μM; α-glucosidase IC₅₀ = 10.75 ± 1.10 μM). Analogs 8g, 8k, and 8b displayed superior or comparable inhibitory activity compared to the reference drug Acarbose. The inhibition potential of the derivatives can be attributed to their stable contacts with crucial amino acid residues of targeted enzymes, as shown through molecular docking analysis. Moreover, DFT-calculated HOMO–LUMO parameters and electrostatic potential (ESP) maps were used to gain complementary insight into the electronic characteristics, charge distribution, and potential interaction behavior of the synthesized derivatives, which supported the molecular docking observations. Conclusions: Experimental outcomes and in silico support display that these derivatives serve as potential leads for anti-diabetic drug development. These potent pyrimidine-derived pyrazole-based thiadiazole derivatives were comparable to an existing diabetic mellitus inhibitor, specifying potential for further therapeutic development and optimization against diabetic mellitus. Full article

A series of 1,2,3-triazole-linked-thiazolidine-2,4-dione hybrids (SDP1–SDP15) were designed, synthesized, and evaluated for their antidiabetic potential. All structures were characterized by FT-IR and NMR spectroscopy (¹H and ¹³C). All derivatives exhibited significant in vitro inhibition of α-glucosidase (IC₅₀: 24.17–46.41 µg/mL) and α-amylase (23.25–50.66 µg/mL), comparable to the standard drug acarbose (IC₅₀: 25.18 and 32.53 µg/mL) and superior to the reference drug pioglitazone (IC₅₀: 84.24 and 79.74 µg/mL) for α-glucosidase and α-amylase, respectively. Molecule SDP8 emerged as the most potent with an IC50 of 24.17 and 23.25 µg/mL for α-glucosidase and α-amylase, respectively. Further, SDP8 exhibited a higher docking score of −10.7 kcal/mol and −10.4 kcal/mol against α-glucosidase and α-amylase than pioglitazone (−8.1 kcal/mol and −7.7 kcal/mol, respectively), suggesting that interaction with these two enzymes may be the cause for its antidiabetic activity. Furthermore, DFT analysis revealed favorable electronic properties with a low HOMO-LUMO energy gap, whereas ADMET predictions revealed moderate drug-like characteristics with some limitations, such as poor solubility, relatively high lipophilicity, and partial noncompliance with drug-likeness regulations. Overall, these results highlight triazole-linked thiazolidinedione hybrids as promising candidates for further development in T2DM, with SDP8 serving as a preliminary lead requiring additional optimization and validation. Full article

The global rise in metabolic disorders demands novel interventions targeting starch digestion. This study investigated two dietary phenolic acids (caffeic acid (CA) and p-hydroxycinnamic acid (p-HA)) as inhibitors of α-amylase and α-glucosidase through integrated experimental and computational approaches. Molecular docking showed distinct binding modes, and CA formed stable hydrogen bonds with catalytic residues of α-glucosidase, while p-HA interacted mainly with α-amylase via hydrophobic contacts. Enzyme kinetics revealed concentration-dependent mixed-type inhibition, with CA being more potent against α-glucosidase and p-HA against α-amylase. Spectroscopic analysis indicated both acids induced structural changes in the enzymes, with CA causing greater α-helix reduction (Δ7.03% vs. Δ2.10%) by altering the tryptophan microenvironment. Moreover, both compounds significantly suppress glucose absorption in the proximal small intestine in an ex vivo everted gut sac model, with p-HA exhibiting exceptional efficacy in the duodenum. These findings clarify structure–activity relationships and support the potential use of CA and p-HA as local intestinal agents for modulating carbohydrate absorption. Full article

Medicinal plants represent a promising source of bioactive compounds with potential antidiabetic activity, while the efficacy of plant extracts depends on both plant matrix and extraction conditions. This study aimed to systematically compare selected medicinal plants and extraction solvents to evaluate their impact on extracts’ in vitro α-amylase inhibitory activity, total polyphenol content (TPC), antioxidant capacity, and antimicrobial properties. Extracts of sage (Salvia officinalis), blueberry leaf (Vaccinium myrtillus), nettle (Urtica dioica), wormwood (Artemisia absinthium), and green and roasted coffee (Coffea arabica) were prepared using different solvent systems (50% (v/v) ethanol, propylene glycol, glycerol, and water), as well as a traditional aqueous infusion protocol. Extraction solvent strongly affected bioactivity: ethanol extracts showed the highest α-amylase inhibition, particularly in sage extract (79.60%) and blueberry leaf (57.71%). No significant correlation with TPC was observed (r = 0.229, p = 0.108), but aqueous ethanol yielded the highest TPC, with blueberry leaf being richest (64.16 ± 0.82 mg GAE/g), followed by roasted coffee (49.36 ± 0.83 mg GAE/g). Ethanol extracts demonstrated antibacterial activity against Staphylococcus aureus. Overall, sage and blueberry leaves showed the most promising multifunctional activity, highlighting their potential for further investigation as functional food ingredients. Full article

Diabetes mellitus is a chronic and increasingly prevalent metabolic disorder characterized by persistent hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. Despite the availability of pharmacological agents that effectively manage blood glucose levels, many are associated with adverse effects, limited efficacy over time, and high costs. Consequently, there is growing interest in alternative therapies, especially those derived from traditional medicinal plants, that have long been employed in various cultures for managing diabetes. Recent advances in phytochemistry have identified bioactive plant secondary metabolites with promising antidiabetic properties. This review aims to provide a comprehensive overview of plant-derived compounds that exhibit inhibitory activity against key diabetes-related enzymes, including α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl peptidase-4 (DPP-4). These enzymes play critical roles in glucose metabolism and insulin signaling pathways. The review highlights the structural diversity of these natural inhibitors, their mechanisms of action, and their effectiveness in preclinical models. Understanding the molecular interactions and pharmacological profiles of these metabolites may facilitate the development of safer and more effective antidiabetic agents. Full article

Thiazolyl-benzene/camphor sulfonamide derivatives (series 4a–k, 5a–j and 6a–i) were synthesized by reaction of various aryl sulfonyl chlorides and camphor sulfonyl chlorides with 2-amino-4-phenylthiazole. The compounds were evaluated for antibacterial, antioxidant, and α-glucosidase/α-amylase inhibitory activities. Biological screening showed that 4h, 5g and 5i displayed significant activity against most Gram-positive bacteria (MICs 4.68–18.75 µg/mL), while 4b and 5i were active against most Gram-negative bacteria with similar MIC ranges. In the DPPH assay, 4e, 4f, 4g and 4h exhibited slightly stronger radical-scavenging activity than ascorbic acid (IC₅₀ ≈ 3.5–3.8 µM vs. 4.14 µM); 5f emerged as the best dual carbohydrate-digesting enzyme inhibitor, and 5b and 5e demonstrated selectivity toward α-amylase. Full article

Zizyphus oxyphylla has been traditionally used in the management of metabolic disorders, and cyclopeptide alkaloids isolated from its roots have been structurally characterized, although their antidiabetic potential remains insufficiently explored. This study evaluated the antidiabetic activity of three previously isolated cyclopeptide alkaloids, Oxyphylline-D (1), Nummularine-C (2), and Nummularine-R (3), using integrated in silico molecular docking and in vitro enzyme inhibition assays. Molecular docking was performed against key diabetes-related enzymes, including α-amylase, α-glucosidase, and dipeptidyl peptidase-4, followed by validation through enzyme inhibition assays. All compounds demonstrated favorable binding affinities toward the selected targets, with compound 2 showing the most consistent performance across enzymes. In vitro results support these findings, where compound 2 exhibited inhibitory activity with IC₅₀ values of 102.97 µg/mL (187.71 µM) against α-amylase and 28.87 µg/mL (52.62 µM) against dipeptidyl peptidase-4, comparable to standard inhibitors. Overall, the results indicate that cyclopeptide alkaloids from Z. oxyphylla possess significant multi-target antidiabetic potential, with Nummularine-C emerging as a promising candidate for further pharmacological development. These findings provide experimental support for computational predictions and reinforce the relevance of combining in silico and in vitro approaches for identifying bioactive natural products with potential therapeutic value in diabetes management, drug discovery pipelines, and development. Full article

Wheat amylase trypsin inhibitors (ATIs) are prominent allergens in Baker’s asthma and contribute to innate inflammation in non-celiac wheat sensitivity (NCWS), linking them to metabolic and autoimmune diseases. Their tetra-, di-, and monomeric forms, stabilized by disulfide bonds, confer resistance to digestion, baking, and heating. Although proteomic studies reveal minor variation in ATI subtypes among cultivars and major variation among species, the influence of environment and wheat genotype on ATI levels and TLR4-stimulating activity remains unclear. We assessed the effect of the environment on the in vitro inflammatory bioactivity of ATIs extracted from 60 German wheat genotypes focusing on breeding over time between 1891 and 2010, and cultivation across three climatically distinct years. We found considerable genotype-dependent variation in ATI bioactivity that did not correlate with ATI subtype abundance, and observed no consistent difference between old and modern cultivars. ATIs from samples grown in 2019, a warm and dry year, showed reduced TLR4 activity, highlighting the significant impact of environmental conditions on inflammatory ATI bioactivity. Full article

Background/Objectives: Ganoderma lucidum (Curtis) P. Karst. (commonly known as reishi mushroom), a well-characterized medicinal fungus, contains diverse bioactive metabolites. This study aimed to fractionate, characterize and identify the biologically active inhibitors present in G. lucidum and to evaluate their antioxidant, antimicrobial, and antidiabetic activities. Methods: The ethanol extract of G. lucidum was fractionated using column chromatography, yielding ten distinct fractions (designated as A, B, E, F, K, L, M, N, O, and P based on their elution order and visual characteristics). Liquid Chromatography–Mass Spectrometry (LC-MS) analysis identified 46 bioactive compounds, including terpenoids, alkaloids, flavonoids, and polysaccharides. Results: Among the fractions, Fraction L exhibited the strongest antioxidant activity, with an IC₅₀ of 1.59 mg/mL. Fraction O displayed significant antibacterial activity against Escherichia coli ATCC 25922 (24.4 ± 0.238 mm), Klebsiella pneumoniae ATCC 13883 (20.5 ± 0.035 mm), Bacillus subtilis ATCC 6633 (8 ± 0.176 mm), and Staphylococcus warneri ATCC 10209 (20 ± 0.080 mm). Regarding antidiabetic activity, Fraction B demonstrated the strongest inhibition of α-amylase (IC₅₀ 1.69 ± 0.03 mg/mL), while Fraction E showed the strongest α-glucosidase inhibition (IC₅₀ = 1.69 ± 0.02 mg/mL), demonstrating reciprocal selectivity between enzyme targets. Conclusions: These results establish that chromatographic fractionation concentrates specific bioactivities into distinct fractions, supporting its potential for the development of novel therapeutic agents with enhanced specificity and efficacy. Full article

Raspberry (Rubus idaeus L.) fruits have been widely used due to their abundance of diverse polyphenolic compounds, whereas research on the chemical composition and bioactivity of their stems and leaves remains limited. In this study, the ethyl acetate extract of raspberry stems and leaves was evaluated for inhibitory activity against α-glucosidase and α-amylase. Guided by affinity ultrafiltration–mass spectrometry, 16 potential active components were further isolated and characterized. Among these, 13 compounds exhibited binding affinity for α-amylase, while 5 compounds showed binding affinity for α-glucosidase. Quercetin-3-O-β-D-glucoside-7-O-β-D-gentiobioside was isolated from raspberry stems and leaves for the first time. Procyanidin C₃ and quercetin exhibited significant inhibitory effects on the two enzymes. Molecular docking studies hinted at the interactions between these compounds and the key active sites of the two enzymes. These findings suggest that phenolic compounds in raspberry stems and leaves may possess potential as α-glucosidase and α-amylase inhibitors, providing a scientific basis for further research on their application as functional components for blood glucose control. Full article