Search Results (1,354)

Background/Objectives: Origanum bilgeri P.H. Davis is a Turkish endemic Lamiaceae species whose non-volatile phenolic composition and organ-specific bioactivities remain unexplored. This study investigated the phenolic composition of flower, leaf, stem, and root extracts and evaluated their antioxidant and enzyme-inhibitory activities. Methods: Ultrasound-assisted ethanolic extracts of the four organs were characterized by liquid chromatography–tandem mass spectrometry (LC–MS/MS) targeting 28 phenolic compounds. Total phenolic and flavonoid contents, outcomes of six antioxidant assays, and inhibitory activities against acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, and α-glucosidase were determined. Measurements were performed in triplicate as technical replicates, and organ-level differences were interpreted descriptively. The relative antioxidant capacity index (RACI) was calculated from the standardized outcomes of the six direct antioxidant assays, with total phenolic content (TPC) and total flavonoid content (TFC) excluded from the index. Pearson correlation analysis and principal component analysis (PCA) were used for exploratory evaluation of phytochemical and bioactivity patterns. Results: Twenty phenolic compounds were detected in at least one organ. Rosmarinic acid predominated in all organs and was most abundant in the leaf (3236 µg/g extract) and stem (3093 µg/g extract), whereas the root was markedly enriched in verbascoside (2775 µg/g extract) and chlorogenic acid (1461 µg/g extract) and exhibited the highest total phenolic content, reaching 160.87 mg gallic acid equivalents (GAE)/g extract. The assay-based RACI ranked the root highest (0.54), followed by the stem (0.02), leaf (−0.27), and flower (−0.30). The root also showed the strongest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (half-maximal inhibitory concentration, IC₅₀ = 0.28 mg/mL) and cupric reducing antioxidant capacity (CUPRAC) (half-maximal effective concentration, EC₅₀ = 0.22 mg/mL) among the investigated organ extracts. Under the present assay conditions, all organ extracts yielded lower α-glucosidase IC₅₀ values (0.97–1.10 mg/mL) than acarbose (1.16 mg/mL). Exploratory Pearson correlation analysis indicated strong organ-level covariation among several antioxidant parameters, phenolic constituents, and α-glucosidase inhibitory activity. PCA based on the Pearson correlation matrix showed that principal components 1 and 2 (PC1 and PC2) accounted for 50.73% and 38.49% of the total variance, respectively (cumulative variance: 89.22%), providing an exploratory visualization of the multivariate organization of phytochemical and bioactivity variables. Conclusions: O. bilgeri exhibited distinct organ-specific phytochemical and bioactivity patterns under the conditions investigated. The root was particularly characterized by high verbascoside and chlorogenic acid contents, elevated total phenolic content, strong antioxidant performance across several assays, and α-glucosidase inhibitory activity. These findings support further investigation of O. bilgeri, particularly its root, using independent biological replicates and complementary phytochemical and biological approaches. Full article

Diabetes mellitus is a long-term metabolic disease associated with elevated glucose levels in blood and still constitutes one of the major public health issues worldwide. Inhibition of carbohydrate-digesting enzymes like α-amylase and α-glucosidase has been found to be effective in controlling postprandial hyperglycemia. The current study focused on designing, synthesis, characterization, and evaluation of novel 2,4-thiazolidinedione derivatives (D1–D5) as potent antidiabetic drugs utilizing combined in silico, in vitro, and in vivo techniques. Results from drug-likeness and ADME analyses indicated that all synthesized derivatives met Lipinski’s rule of five and had desirable pharmacokinetics properties along with reduced toxicity. Molecular docking against maltase-glucoamylase (human; PDB ID: 3TOP) protein showed good binding affinities of both D1 and D5 derivatives (−7.74 and −7.40 kcal/mol respectively) due to stable interactions with catalytic residues of enzymes. Inhibition of enzymes in vitro showed that D1 and D5 had the highest inhibitory activities of all synthesized derivatives, with IC₅₀ of 33.86 ± 2.1 and 37.55 ± 1.7 μM against α-amylase and 29.81 ± 3.2 and 32.43 ± 1.2 μM against α-glucosidase, respectively. Cytocompatibility tests on L6 myoblast cells proved that the lead compounds were well tolerated. In addition, studies in a model of Drosophila melanogaster induced by a high-sugar diet revealed a significant decrease in the level of glucose concentration depending on the dose, especially for D1 and D5, indicating their antihyperglycemic activity in vivo. Thus, these data confirm that D1 and D5 can be regarded as promising lead compounds for the development of new antidiabetics acting via inhibition of carbohydrate-metabolizing enzymes. Full article

Type 2 diabetes mellitus (T2DM) remains a major clinical challenge, with postprandial hyperglycemia (PPG) playing a key role in the development of vascular complications. Current pharmacotherapies often do not sufficiently control PPG, highlighting the need for complementary strategies. One effective approach is the inhibition of carbohydrate digesting enzymes, α-amylase and α-glucosidase, which delays glucose absorption and reduces PPG excursions. Flavonoids, a diverse class of plant-derived polyphenols, exhibit multiple biological activities relevant to T2DM, including enzyme inhibition, antioxidant, and anti-inflammatory effects. This review summarizes the mechanisms by which flavonoids modulate glucose metabolism, with particular emphasis on their interactions with α-amylase and α-glucosidase. Structure–activity relationships are discussed, focusing on the influence of hydroxylation patterns, conjugation, and molecular planarity on inhibitory potency and selectivity. Selected flavonoids—chrysin, apigenin, luteolin, and quercetin—are comparatively analyzed in terms of enzyme inhibition profiles, binding mechanisms, and selectivity. Evidence from in vitro studies, enzyme kinetics, and molecular docking highlights their differential activity, particularly the preferential inhibition of α-glucosidase over α-amylase, which may reduce gastrointestinal side effects. Overall, flavonoids represent promising modulators of PPG. However, their clinical relevance is limited by bioavailability and variability of experimental data, warranting further investigation. Full article

The aerial parts of Nanhaia speciosa are often discarded despite their potential as a source of bioactive compounds. This study aimed to characterise this underutilised biomass and evaluate its functional properties relevant to carbohydrate digestion. Ultra-high-performance liquid chromatography–quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), Global Natural Products Social (GNPS) molecular networking, and MS/MS fragmentation analysis tentatively annotated 96 compounds, mainly flavonoids and nitrogen-containing constituents. The extract inhibited α-glucosidase and α-amylase in a concentration-dependent manner, with IC₅₀ values of 9.98 ± 0.02 and 174.83 ± 1.31 μg/mL, respectively, compared with 29.73 ± 0.04 and 39.46 ± 0.19 μg/mL for acarbose. The extract also showed measurable chemical antioxidant capacity. Network pharmacology suggested potential involvement of cAMP-, calcium-, and receptor-associated signalling. Molecular docking prioritised butein as a candidate constituent with favourable predicted interactions with both enzymes, and molecular dynamics simulations supported stable predicted binding. The estimated MM/GBSA binding free energies of butein were −36.68 and −32.03 kcal/mol for α-glucosidase and α-amylase, respectively. These findings indicate that the aerial biomass of N. speciosa is a promising source of phytochemicals with potential carbohydrate-hydrolase inhibitory properties, although the activity of individual constituents requires further experimental validation. Full article

The argan tree (Argania spinosa) is an endemic Moroccan species known for its primary product, argan oil, which possesses exceptional nutritional and medicinal properties. The current study aimed to evaluate and compare the antidiabetic and antioxidant activities of argan oil obtained from the introduced and native argan tree in eastern Morocco, to analyze its chemical composition using HPLC-DAD and GC-MS, and to investigate the molecular mechanisms behind the obtained pharmacological activities through an in silico pharmacological networking and molecular docking study. The results revealed that argan oil from all three regions of Morocco (Oujda, Agadir, and Chouihya) is rich in oleic and linoleic acids as major constituents, along with the presence of significant tocopherols. Regarding the antioxidant assays, including DPPH radical scavenging and iron-reducing power tests, argan oil from Oujda exhibited the highest activity, with the lowest IC₅₀ values of 15.25 ± 0.022 mg/mL and 28.5 ± 1.7 mg/mL, respectively. Concerning the antidiabetic activity, we found that oil from Chaouihya showed the strongest α-amylase inhibition, while Oujda oil had the highest antiglycation activity, indicating that even introduced argan trees retain potent bioactivity. The results of the in silico investigation suggested that tocopherols may contribute to the antioxidant and antidiabetic potential of argan oil, showing predicted antioxidant activity (Pa = 0.843–0.967) and favorable binding affinities toward iNOS (ΔG = −9.3 kcal mol⁻¹) and α-glucosidase (ΔG = −8.2 kcal mol⁻¹). The identified fatty acids also showed predicted insulin-promoting activity (Pa = 0.59–0.75) and moderate enzyme-binding potential. Pharmacological network analysis identified 51 shared genes associated with antioxidant, antidiabetic, and argan-related targets, with enrichment of the AGE–RAGE signaling pathway. These computational findings provide possible molecular associations that may help explain the observed biological activities, although they remain predictive and require experimental validation. Overall, the in silico analysis suggests that tocopherols could be among the contributors to the multi-target profile of Argania spinosa oil, while fatty acids may provide complementary effects related to glycemic regulation. Full article

Mung bean seed coat (MBSC) is a byproduct of commercial vermicelli production that possesses essential activities capable of delaying diabetic wound progression. This study aimed to evaluate the potential of MBSC extracts to promote diabetic wound healing, an effect that has not yet been reported. The hypoglycemic effect was assessed by glucose uptake stimulation in L6 myotubes and by an α-glucosidase inhibition assay. Antiglycation was determined by BSA-glucose and BSA-methylglyoxal assays. Intracellular reactive oxygen species (ROS) reduction and wound healing were assessed in human keratinocytes (HaCaT) exposed to high glucose (HG), and gene expression in HG-wounded cells was analyzed by qPCR. The results demonstrated that the ethanolic extract (EE) from MBSC exhibited glucose-lowering effects and suppressed glycation reactions at the early and intermediate stages, with IC₅₀ values of 75 and 140 µg/mL, respectively. EE reduced ROS by 70%, stimulated cell proliferation by 57% in the high-glucose (HG)-exposed HaCaT cells, and accelerated cell migration to close the HG-exposed wound. EE increased the gene expression of Nrf2, NQO-1, SOD2, and CAT. It also downregulated TNF-α, upregulated TGF-β1, and downregulated MMP-9. In conclusion, EE has the potential to delay the progression of diabetic wounds by lowering blood glucose levels, inhibiting AGE and ROS formation, and enhancing cell proliferation and migration in HG-exposed HaCaT cells. The gene regulatory effects of EE were demonstrated as an Nrf2 activator that reduced oxidative stress, exerted anti-inflammatory effects, and regulated ECM balance. The preparation of oral and topical products could be further developed. Full article

Diabetes mellitus is a major global health challenge, and medicinal plants represent an important source of bioactive compounds with therapeutic potential. Ibervillea sonorae (S. Watson) Greene is traditionally used in Mexican medicine for diabetes management and has attracted increasing scientific interest because of its reported antihyperglycemic activity. This systematic review critically evaluated the available preclinical evidence regarding the antihyperglycemic effects of I. sonorae, its proposed molecular mechanisms, phytochemical context, and methodological limitations. Following the PRISMA 2020 guidelines, PubMed, Scopus, and Google Scholar were searched for studies published between January 2010 and February 2026. Eight studies met the inclusion criteria, including animal, cellular, and enzyme-based models. The available evidence indicates that I. sonorae preparations may improve glycemic control through complementary mechanisms involving enhanced glucose uptake and insulin-related responses, including participation of the PI3K/AKT/GLUT4 signaling network, together with inhibition of α-glucosidase and α-amylase activity. AMPK-related mechanisms remain biologically plausible but have not been directly established across the included studies. Phytochemical evidence identifies cucurbitacin-derived constituents, including kinoins, as potentially relevant bioactive compounds; however, most mechanistic findings were obtained using crude extracts or other plant preparations, and their specific contribution cannot yet be attributed to individual constituents. Overall, this review integrates the fragmented preclinical evidence and identifies the principal mechanistic, phytochemical, and methodological gaps that must be addressed before clinical translation. I. sonorae represents a promising candidate for antihyperglycemic research, although phytochemical standardization, rigorous mechanistic studies, comprehensive safety evaluation, and well-designed clinical investigations are required to establish its therapeutic efficacy and safety. Full article

Type 2 diabetes mellitus (T2DM) is a major global health challenge, which has increased interest in functional foods containing bioactive compounds with antidiabetic potential. This study evaluated the in vitro antidiabetic activity of phenolic compounds extracted from SunGold kiwifruit using a choline chloride–glycerol natural deep eutectic solvent (NADES) and their application in yoghurt. NADES and water extracts were assessed for α-glucosidase and α-amylase inhibition and glucose diffusion retardation. The extracts were incorporated into yoghurt at different concentrations before or after fermentation, followed by assessment of enzyme-inhibitory activities and phenolic profiles. The NADES extract showed stronger α-glucosidase and α-amylase inhibition than the water extract, with IC₅₀ values of 15.331 ± 0.393 and 116.530 ± 2.110 mg/mL, respectively. It also produced greater glucose diffusion retardation at 180 min (62.84%) than the water extract (37.89%). Fortification enhanced enzyme-inhibitory activities in a concentration-dependent manner, with post-fermentation yoghurt containing 30% NADES extract showing the highest α-glucosidase and α-amylase inhibitory activities of 3.615 ± 0.032 mg QE/g and 111.186 ± 0.541 mg AE/g, respectively. LC-MS/MS identified catechin, epicatechin, epigallocatechin, chlorogenic acid, caffeic acid, and gallic acid. These findings demonstrate that the NADES preparation showed greater in vitro carbohydrate-digestive enzyme inhibition and glucose diffusion retardation than the water extract under the tested conditions. Full article

Diabetes mellitus is a pervasive global health crisis, with type 2 diabetes (T2D) representing the majority of cases. While conventional pharmacological therapies exist, suboptimal efficacy, adverse effects, and inadequate glycemic control in a substantial proportion of patients highlight the need for complementary strategies. There is growing scientific and clinical interest in plant-based functional foods, including Ribes nigrum L. (blackcurrant), which is rich in bioactive phytochemicals such as anthocyanins, flavonols, and phenolic acids. This review evaluates the antidiabetic and metabolic regulatory potential of blackcurrant, focusing on its multi-target mechanisms of action. Available experimental evidence suggests that blackcurrants may influence glucose metabolism through several mechanisms, including inhibition of carbohydrate-digesting enzymes (α-amylase and α-glucosidase), modulation of intestinal glucose transporters (SGLT1 and GLUT2), and potential modulation of insulin sensitivity involving AMPK signaling and GLUT4 translocation. In addition, blackcurrant constituents may stimulate glucagon-like peptide-1 (GLP-1) secretion, modulate gut microbiota composition, and exert antioxidant and anti-inflammatory effects that counteract key drivers of insulin resistance and β-cell dysfunction. Supporting human studies indicate that blackcurrant consumption has been associated with attenuation of postprandial glycemic and insulinemic responses and modest improvements in cardiometabolic biomarkers, although findings remain limited by study size, duration, and formulation heterogeneity. Overall, Ribes nigrum represents a promising dietary adjunct for the prevention and management of T2D through multi-target metabolic regulation. Full article

Six representative small-molecule constituents were isolated and structurally characterized from the edible mushroom Tremella fuciformis: cis-oleic acid (1), 1-oleoylglycerol (2), cerevisterol (3), a cerebroside (4), trans-homoaconitic acid (5), and uridine (6). Compound 5, a tricarboxylic acid derivative, is reported for the first time as abundantly accumulated in this fungus. Aging-relevant assays showed that 1 potently inhibited α-glucosidase (IC₅₀ = 0.02 mM, surpassing acarbose) and moderately inhibited acetylcholinesterase (IC₅₀ = 0.29 mM); 5 competitively inhibited alkaline phosphatase (IC₅₀ = 5.47 mM) and suppressed GluN2A-containing NMDA receptor currents (IC₅₀ = 0.40 mM), the first such dual report for a fungal tricarboxylic acid; and 4 inhibited tyrosinase (IC₅₀ = 0.80 mM) comparably to kojic acid. HPLC confirmed meaningful recovery under mild hydro-alcoholic extraction compatible with functional food processing. These multifunctional small molecules target carbohydrate metabolism, cognition, and skin homeostasis, supporting T. fuciformis as a source of healthy-aging food ingredients. Full article

Total flavonoids (TF) from Artemisia argyi, a traditional edible-medicinal Asteraceae herb, were extracted via a food-grade ternary deep eutectic solvent (TDES, Glycerol/Levulinic Acid/Xylitol = 1:1:1 molar ratio, 30% w/w water) under ultrasound assistance. A hybrid response surface methodology–genetic algorithm–artificial neural network (RSM-GA-ANN) model optimized parameters to deliver a maximum TF yield of 107.7 mg/g—1.5–1.8-fold higher than conventional hydroalcoholic extraction. Greenness was quantified by AGREEprep (score = 0.70) and MoGAPI (score = 80/100), confirming the method’s sustainability, with TDES retaining >84% extraction efficiency over three reuse cycles. Molecular dynamics simulations revealed TDES forms a more stable hydrogen bond network with plant cell walls (average H-bond lifetime: 101.279 ps vs. 46.698 ps for 50% ethanol), a finding validated by density functional theory calculations showing TDES establishes 7–9 hydrogen bonds with cellobiose (the cellulose repeating unit), far exceeding ethanol’s 1–2 hydrogen bonds. Purified TF exhibited potent radical-scavenging activity (DPPH IC₅₀: 0.176 mg/mL; ABTS IC₅₀: 0.159 mg/mL) and multipotent enzyme inhibition (α-glucosidase IC₅₀: 55.31 μg/mL; acetylcholinesterase IC₅₀: 0.618 mg/mL; pancreatic lipase IC₅₀: 0.125 mg/mL). TF also suppressed HCT116, A549, and HepG2 proliferation (IC₅₀ ≈ 50 μg/mL) and protected HepG2 cells against H₂O₂-induced oxidative damage. As an in silico probe, the predominant quantified flavonoid eupatilin (3.64 mg/g) docked to xanthine oxidase (−7.78 kcal/mol vs. allopurinol −6.86), offering a structural hypothesis for XO interaction without attributing mixture bioactivity to a single compound. This TDES-based platform offers a scalable, green route to valorize A. argyi for functional food and nutraceutical applications. Full article

This study aimed to illustrate the effects of plant-based yogurts made from bio-fermentative green rice milk yogurt (GRMY), enhanced with Wolffia globosa powder (WGP) and infused with Thai green tea. Different formulations (F1 to F4) were analyzed to assess the impact of varying weight ratios of WGP, ranging from 0% to 15%. The goal was to improve nutritional values and bioactive components. The F4 formulation of plant-based yogurt demonstrated enhanced nutritional values, including higher levels of dietary fiber, starch, protein, and fat contents, which were 42.45, 26.55, 22.48, and 2.29% DW, respectively. It was increased by bioactive compounds such as total phenolic content (52.99 mg GAE/g), total flavonoid content (60.45 mg QUE/g), and β-carotene (1.81 mg/g). Additionally, the F4 formulation exhibited the highest antioxidants in terms of DPPH activity (5.48 mg TROE/g), ABTS activity (424.15 mg TROE/g), and FRAP reducing capacity (106.35 mg TROE/g) and antidiabetic activity of α–glucosidase inhibition in IC₅₀ at 1.41 mg/mL. The yogurts were evaluated through metabolomic network analysis as a complex bioactive food system, wherein fermentation-derived metabolites synergistically interact with tea polyphenols, amino acids, phytosterols, and carotenoids. The prevailing metabolic profiles indicate an increase in antioxidant capacity, a reduction in inflammatory burden, enhanced glucose metabolism, alterations in gut microbiota, cardiovascular protection, and neuroprotective potential. These findings suggest that the product represents a promising plant-based functional food, offering numerous health benefits. This assertion is supported by a diverse metabolite network identified through UPLC–MS/MS metabolomic research. Full article

Flavones are natural substances widely distributed in fruits and vegetable. Their compounds are characterized by a broad spectrum of activities, including antioxidant activity. Their most interesting biological effect, however, is antihyperglycemic activity, mediated by the inhibition of α-glucosidase. A series of 7-hydroxyflavone derivatives was synthesized and comprehensively characterized using nuclear resonance magnetic spectroscopy. The biological potential of the synthesized derivatives was assessed through antioxidant (DPPH) and α-glucosidase inhibitory assays. The physicochemical and pharmacokinetic properties were analyzed using in silico methods. Finally, molecular docking studies were performed to elucidate the binding mode of compounds within the catalytic site of α-glucosidase. Full article

A novel, uniform acid heteropolysaccharide with a molecular weight of 13.14 kDa was isolated from the fermented broth of the mangrove endophytic fungus Penicillium janthinellum N29, designated as PJ3-1. A structural analysis showed that PJ3-1 is a straight-chain heteropolysaccharide containing GlcN, GlcNAc, Glc and GlcA in the ratio of 12.23:1.79:10.93:1.00. PJ3-1 markedly inhibits α-glucosidase activity and relieves insulin resistance in HepG2 cells. It alleviates lipid peroxidation and upregulates the activities of endogenous antioxidant enzymes. In addition, it also significantly scavenges hydroxyl radicals, ferrous ions, superoxide anions, DPPH radicals and ABTS radicals and enhances reducing power in a dose-dependent manner. Collectively, these findings suggest that PJ3-1 has the potential to serve as a natural antioxidant and hypoglycemic agent for functional food or pharmaceutical applications. Full article

1-Deoxynojirimycin (DNJ), a well-characterized α-glucosidase inhibitor, remains an important target for dose-reduction and formulation strategies. In the present study, we evaluated the individual and combined α-glucosidase inhibitory activities of nine dietary flavonoids with DNJ, quantified synergistic effects using the combination index (CI) method, and elucidated the molecular mechanism through integrated enzyme kinetics, multi-spectroscopic techniques and molecular docking. (+)-Catechin exhibited the strongest inhibitory activity (IC₅₀ = 33.7 ± 2.7 μM), and its combination with DNJ produced synergistic inhibition across all doses (CI < 0.7). Kinetic analysis confirmed that DNJ acted as a competitive inhibitor, while (+)-catechin functioned as a non-competitive inhibitor. Fluorescence quenching assays revealed that (+)-catechin pre-incubation increased the binding affinity of DNJ to α-glucosidase by 393%. Circular dichroism spectroscopy showed that (+)-catechin induced a marked β-sheet-to-α-helix conformational conversion, and co-incubation of both inhibitors produced more secondary structural changes than either inhibitor alone. Molecular docking further confirmed their distinct binding sites. These findings demonstrate that (+)-catechin synergistically potentiates DNJ activity through allosteric conformational modulation, providing an experimental basis for optimizing DNJ-containing formulations. Full article