Search Results (1,345)

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

Background/Objectives: Diabetes mellitus is a common endocrine disorder characterized by hyperglycemia, which is increasing steadily all over the world. Current medications are limited due to lower efficacy and side effects; therefore, the introduction of novel compounds is crucial to improve therapeutic outcomes for diabetic patients. The objective of this study was to synthesize and evaluate 2-phenyl-3H-quinazolin-4-one and its derivatives for the glucose uptake across the yeast cell membranes, alpha-amylase inhibition, and alpha-glucosidase inhibition in silico and in vitro. Methods: The synthesis of 2-phenyl-3H-quinazolin-4-one and its derivatives was carried out by oxidative cyclocondensation of 2-aminobenzamide (anthranilamide) with various benzaldehydes in the presence of aqueous iron (III) chloride. The synthesized compounds were characterized by melting point determination and spectroscopic techniques, including FTIR, NMR and HRMS. Results: In the glucose uptake by yeast assay, compound 3f had a lower 50% glucose uptake value of 24.02 ± 0.96 mM, compared with the standard drug metformin (25.99 ± 2.41 mM). The alpha-amylase inhibition bioassay showed that compound 3e exhibited very potent inhibition, with an IC₅₀ of 0.43 ± 0.05 mM, compared with the standard drug acarbose (0.53 ± 0.21 mM). Compound 3l exhibited strong alpha-glucosidase inhibition, with an IC₅₀ of 0.42 ± 0.10 mM, compared with the standard drug acarbose (0.29 ± 0.50 mM). Coclusions: These findings suggest the potential of synthesized 2-phenyl-3H-quinazolin-4-one derivatives, 3a–o, as promising candidates for managing diabetes mellitus. However, further studies are required to validate their efficacy and determine their mechanisms of action. Full article

Astragalus species have long been recognized for their pharmacological relevance, yet the antidiabetic properties of Astragalus cruciatus Link (Ac) remain poorly explored. This study aimed to investigate the antidiabetic potential of A. cruciatus Link and to elucidate possible underlying mechanisms. The ethanolic extract of Ac (AcEE) was prepared and analyzed for phenolic and flavonoid content. Antioxidant activity was assessed through a series of in vitro assays. The in vitro inhibition of α-amylase and α-glucosidase was assessed, followed by molecular docking to probe ligand-enzyme interactions. LC-ESI-MS analysis revealed a polyphenol-rich profile, with rutin (953.54 µg/g extract) and quinic acid (797.18 µg/g of extract) identified as main compounds. The AcEE showed significant inhibitory activity against both α-amylase and α-glucosidase (IC₅₀ = 239.30 ± 7.40 and 192.60 ± 15.51 μg/mL, respectively). Moreover, low cytotoxic effects were observed in hepatic cell lines. Computational analysis revealed stable interactions between rutin and both enzymes (−12.935 and −8.073 Kcal/mol, respectively). Network pharmacology revealed that AcEE may modulate key targets, including IL-6, TNF-α, IL-1β, Akt-1, STAT3, EGFR, and INSR as well as pathways related to insulin resistance, AGE-RAGE, and inflammation. These findings suggest that AcEE exerts significant antidiabetic effects through multitarget modulation, highlighting its potential as a natural therapeutic agent for T2DM. Full article

Fucoidans are sulphated polysaccharides from brown macroalgae that have attracted considerable interest due to their diverse biological activities and potential applications in metabolic health. In this study, fucoidan-rich extracts were obtained from three South African brown macroalgal species, Ecklonia maxima, Ecklonia radiata, and Sargassum incisifolium, and comparatively characterised using biochemical and physicochemical analyses. The extracts were evaluated for carbohydrate, sulphate, L-fucose, protein, polyphenol, and uronic acid contents, while molecular weight distribution, Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and proton Nuclear Magnetic Resonance (¹H NMR) spectroscopy were used to investigate structural characteristics. All extracts displayed features characteristic of fucoidans, including sulphated fucose-containing polysaccharides. Notable species-dependent differences were observed, with S. incisifolium exhibiting the highest sulphate (~24%) and polyphenol (~6.76%) contents, stronger sulphate-associated FTIR signals, greater molecular weight heterogeneity, and enhanced thermal stability. The fucoidan-rich extracts exhibited concentration-dependent pancreatic lipase and α-glucosidase inhibitory activities, together with DPPH radical-scavenging activity. At 1.0 mg/mL, S. incisifolium demonstrated approximately 66% DPPH radical scavenging and 49% pancreatic lipase inhibition. S. incisifolium and E. radiata exhibited strong α-glucosidase inhibition, with IC₅₀ values of ~29 and ~46 µg/mL, respectively, compared to ~354 µg/mL for acarbose. The findings highlight South African brown macroalgae as promising sources of fucoidans and contribute to understanding the relationships among fucoidan composition, structure, and bioactivity. Full article

This study introduces a novel food-grade protein–β-glucan nanoparticle system based on Fusarium venenatum protein isolate and Fuscoporia torulosa β-glucans, designed as a multifunctional ingredient for improving the physicochemical stability, bioaccessibility, and functional performance of peach juice beverages. Therefore, this study aimed to develop and evaluate a functional peach juice enriched with protein–β-glucan nanoparticles and to investigate their effects on physicochemical stability, gastrointestinal behavior, metabolic enzyme inhibition, antioxidant retention, and sensory acceptance. Protein–β-glucan nanoparticles produced from Fusarium venenatum protein isolate and Fuscoporia torulosa β-glucans were incorporated into peach juice formulations (V1–V4) and characterized using dynamic light scattering, zeta potential analysis, transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR). In vitro gastrointestinal digestion was performed to assess β-glucan bioaccessibility, protein digestibility, antioxidant activity, and release kinetics, while α-amylase and α-glucosidase inhibition assays, sensory evaluation, digital sensory analysis, principal component analysis (PCA), and exploratory multivariate analysis were used to evaluate relationships among formulation characteristics and functional performance. The nanoparticles formed stable colloidal systems with mean particle sizes ranging from 176 to 229 nm and maintained structural integrity during 28 days of refrigerated storage. Nanoparticle-enriched formulations exhibited higher β-glucan bioaccessibility, improved antioxidant retention, and stronger α-amylase and α-glucosidase inhibitory activities, with the greatest effects observed in V4. Protein digestibility remained high across all formulations, while sensory evaluation revealed improved overall liking and purchase intention. PCA indicated that nanoparticle concentration was the main factor differentiating the formulations based on their physicochemical and functional characteristics. Overall, protein–β-glucan nanoparticles enhanced the physicochemical, functional, and sensory properties of peach juice, supporting their application as multifunctional ingredients for functional beverage development. Full article

Ficus deltoidea Jack (Moraceae), locally known as Mas Cotek, is a medicinal plant traditionally used throughout Southeast Asia for the management of diabetes mellitus. This review summarises the available evidence on the antidiabetic properties of F. deltoidea based on eleven in vitro, nine in vivo and one clinical study identified through a structured literature search. In vitro investigations show that F. deltoidea inhibits α-glucosidase and α-amylase, stimulates insulin secretion in pancreatic β-cells via both K⁺-ATP channel-dependent and -independent pathways, enhances glucose uptake in hepatocytes and adipocytes, promotes adiponectin secretion and inhibits protein tyrosine phosphatase 1B (PTP1B). Vitexin and isovitexin, the predominant C-glycosyl flavonoids in F. deltoidea leaves, appear to be the main bioactive compounds responsible for these effects. Meanwhile, in vivo studies in streptozotocin-induced diabetic rodents report dose-dependent reductions in fasting blood glucose, improved glucose tolerance, restoration of pancreatic islet architecture, modulation of hepatic gluconeogenic and glucose-metabolic genes, and protection against diabetic nephropathy and bone loss. Inter-varietal differences in chemical composition and biological activity were observed, with var. trengganuensis and var. intermedia reported as the most active. The only available clinical trial in adults with prediabetes (1000 mg/day for 8 weeks) showed a reduction in LDL and total cholesterol but no significant change in fasting blood glucose or insulin. The discrepancy between preclinical and clinical findings highlights the need for standardised extracts, pharmacokinetic studies and adequately powered clinical trials in patients with established type 2 diabetes mellitus. Full article

High fructose intake rapidly induces protein glycation, oxidative stress, inflammation, and disturbances in the cultivable fraction of gut bacteria, contributing to early metabolic impairment. This study examined whether selected plant-derived bioactives and a prebiotic–probiotic formulation could mitigate fructose-induced biochemical and microbial alterations. Male Wistar rats were fed fructose for 45 days, and advanced glycation end product (AGE)-associated fluorescence, oxidative stress markers, and lipid peroxidation were measured to assess metabolic changes. Culture-dependent enumeration of intestinal and fecal bacteria was performed to evaluate shifts in cultivable aerobic and facultative bacterial counts, while limonene, eugenol, and emodin were tested for antibacterial activity against aerobic and facultative bacterial isolates obtained from fructose-fed rats during our previous study. The prebiotic–probiotic formulation was assessed alone and in combination with these bioactives. Fructose feeding increased protein glycation, oxidative stress, lipid peroxidation, and reduced counts of cultivable gut bacteria. Treatment with the bioactives and the formulation lowered glycation-related fluorescence, reduced oxidative stress, and decreased lipid peroxidation. The bioactives exhibited antioxidant and antiglycation activity and inhibited growth of selected cultivable bacterial isolates, including Corynebacterium stationis. While emodin contributed primarily through its known α-glucosidase inhibitory and antiglycation properties rather than antibacterial activity. Combined treatment partially restored cultivable bacterial counts and improved metabolic parameters. Overall, the interventions attenuated fructose-induced biochemical disturbances and modulated the cultivable gut bacterial counts, suggesting a complementary approach to managing early metabolic changes in rats associated with high fructose intake. Full article

Type 2 diabetes (T2D) remains a major public health challenge in Africa, where limited healthcare access and the high cost of conventional therapies sustain reliance on African traditional medicine (ATM). This systematic review and meta-analysis evaluated the efficacy, mechanisms of action, and safety of African polyherbal formulations for T2D management. This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines, following a protocol registered with PROSPERO (CRD420251168831). We searched PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar for studies published between 1 January 2011 and 31 December 2024. Seventeen studies met the inclusion criteria. Polyherbal formulations consistently improved glycaemic control, insulin sensitivity, antioxidant status, and lipid profiles. Meta-analysis of 10 preclinical studies demonstrated a significant reduction in fasting blood glucose compared with that of diabetic controls (SMD = −5.22, 95% CI: −5.55 to −4.89; p < 0.001; I² = 93.88%). Proposed mechanisms included β-cell protection, stimulation of insulin secretion, inhibition of α-amylase and α-glucosidase, and attenuation of oxidative stress. Safety data were limited and inconsistently reported. Human evidence was limited to one quasi-experimental clinical study and one acute human OGTT study. African polyherbal formulations demonstrate promising antidiabetic potential; however, methodological heterogeneity, limited phytochemical characterisation, inadequate safety assessment, and scarce clinical evidence highlight the need for standardised preclinical studies and well-designed clinical trials to support evidence-based integration into healthcare. 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

The global rise in obesity and associated metabolic disorders has fueled the demand for safe, multi-target therapeutics derived from natural sources. In this study, an artificial neural network combined with a genetic algorithm (ANN-GA), was employed to optimize the ultrasound-assisted extraction of loquat leaf extract (LLE). The optimal parameters—0.6% Tween 80, 328 W ultrasonic power, and 49 °C—enhanced extraction efficiency while minimizing energy consumption and surfactant use. In vitro, LLE exhibited potent dose-dependent inhibition of α-glucosidase (IC₅₀ = 3.75 μg/mL, 21.6-fold stronger than acarbose) and pancreatic lipase (IC₅₀ = 78.3 μg/mL), indicating strong inhibitory activity against these digestive enzymes. In high-fat diet-induced obese mice, LLE supplementation dose-dependently reduced body weight gain, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose while elevating high-density lipoprotein cholesterol (HDL-C). In addition, LLE ameliorated liver injury (decreased ALT/AST) and oxidative stress (lowered MDA, increased SOD). These findings highlight LLE as a promising multi-target natural product for managing obesity and related metabolic disorders. Full article