Search Results (447)

Annona cherimola is a plant species widely used in Mexican traditional medicine, particularly in the management of diabetes. This study aimed to investigate the antihyperglycemic properties of the petroleum ether extract of A. cherimola leaves (PEEAcL), as well as to evaluate their effects on glycated hemoglobin and toxicity. In addition, the work was directed to determine its potential as an SGLT-1 and α-glucosidase inhibitor. The effect as a potential SGLT-1 and α-glucosidase inhibitor of PEEAcL was evaluated utilizing intestinal glucose absorption (IGA), oral glucose tolerance (OGT), oral sucrose tolerance (OST) and intestinal sucrose hydrolysis (ISH) tests. PEEAcL administered at doses of 200 mg/kg showed significant antihyperglycemic activity after 1 h of treatment, and the maximum effect was seen at 4 h in male and female diabetic mice. In the OST, OLT, and OGT tests, PEEAcL generated a reduction in the postprandial glucose peak at 2 h after the administration of a carbohydrate load, showing an effect comparable to that of acarbose and canagliflozin. In the IGA trial, PEEAcL significantly reduced glucose uptake in the small intestine. Similarly, in the ISH, PEEAcL recorded a significant reduction in glucose concentration in the external aqueous medium. Taken together, these results suggest that the antihyperglycemic effect of PEEAcL could be mediated, at least in part, by inhibition of SGLT-1 and the enzyme α-glucosidase. Full article

Background/Objectives: Onion (Allium cepa) peems are an underutilized by-product rich in polyphenols. This study evaluated the physicochemical profile, and bioactive potential (antidiabetic, antimicrobial, antioxidant, and anticoagulant) of Moroccan red onion peels using integrated in vivo, in vitro, and in silico approaches. Methods: Moisture, pH, ash content, and mineral elements were determined, followed by phytochemical screening and three extractions: decoction E0, aqueous Soxhlet E1, and hydroethanolic Soxhlet E2 (70/30; ethanol/water, v/v). The measurement of polyphenols, flavonoids, and tannins was carried out using colorimetric methods, while the molecular profile was studied by high-performance liquid chromatography coupled to ultraviolet detection and electrospray ionization mass spectrometry (HPLC/UV-ESI-MS). Biological activities were determined using 2,2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and total antioxidant capacity assays (in vitro antioxidant); microdilution (antimicrobial); prothrombin time and activated partial thromboplastin time (anticoagulant); and α-amylase/α-glucosidase enzymatic inhibition and oral glucose tolerance tests on normoglycemic rats. Also, acute toxicity was evaluated, and molecular interactions between these proteins and ligands (docking, molecular dynamics, and MM-PBSA) were analyzed. Results: Physicochemical analyses showed an acidic pH (3.06) and high ash content (15.21%), with the concentration of regulated elements remaining within FAO/WHO limits. The extractive content was between 6.90% E0 and 19.18% E2. The E1 extract had the maximum amount of total polyphenols (178.95 mg GAE/g); on the other hand, E2 was the richest in flavonoids by 121.43 mg QE/g. The HPLC/ESI-MS analysis of E0 revealed 20 compounds, among which flavonoids (84.93%) were predominant, with isorhamnetin (30.26%), followed by quercetin and its glycosylated forms. E1 showed the most potent antioxidant effects (IC₅₀ DPPH, 22.38 µg/mL, as that of ascorbic acid). The antibacterial activity of E0 was especially potent towards Enterobacter cloacae and Pseudomonas aeruginosa (MIC 75 µg/mL). A mild dose-dependent anticoagulant effect was seen. Antidiabetic activity was found to be outstanding: α-amylase (IC₅₀ 62.75 µg/mL) and α-glucosidase (IC₅₀ 8.49 µg/mL, stronger than acarbose) inhibitions were corroborated in vivo by a considerable decrease in the glycemic area under the curve. The molecular docking study in silico demonstrated strong molecular interactions, especially for quercetin 4′-O-glucoside with good binding energies. Conclusions: A. cepa peels from Morocco can be considered a safe plant matrix containing bioactive flavonoids with strong antioxidant and selective antimicrobial activities and promising antidiabetic effects, supported by molecular modeling. Full article

Momordica balsamina Linn. is widely used in traditional medicine for the management of diabetes; however, the specific bioactive compounds responsible for this activity have not been fully isolated and structurally elucidated from South African populations. This study reports, for the first time, the isolation and comprehensive characterization of antidiabetic compounds from South African samples of M. balsamina. Crude extracts were obtained through sequential solvent extraction, followed by isolation and purification using vacuum liquid chromatography. Structural elucidation was achieved using HPLC, UPLC–MS, FTIR, and NMR spectroscopy. The antidiabetic potential of the isolated compounds was evaluated through inhibition assays against α-amylase, α-glucosidase, and β-glucosidase. Molecular docking was employed to examine binding interactions with these target enzymes, while cytotoxicity was assessed using the MTT assay against Vero and HEK-293 cell lines. Two compounds, DD26.27 and EAEA1.2, were successfully isolated from dichloromethane and ethyl acetate extracts, respectively. Both compounds demonstrated concentration-dependent inhibition of the tested enzymes. Notably, molecular docking revealed strong binding affinities and favorable interactions with key catalytic residues, surpassing the standard drug acarbose and corroborating the in vitro results. Cytotoxicity studies confirmed that, at lower concentrations, the compounds were non-toxic to the tested cell lines. Collectively, these findings provide novel scientific validation of the traditional use of M. balsamina in South Africa and identify promising lead compounds for further in vivo studies and antidiabetic drug development targeting postprandial hyperglycemia. Full article

In this study, the Box–Behnken Design (BBD) was adopted to optimize the ultrasound-assisted extraction (UAE) conditions of polyphenols from Hericium erinaceus (H. erinaceus) on the basis of single-factor experiments, with extraction time, solid–liquid ratio and ethanol concentration as the key investigation factors. The optimal extraction parameters were determined as follows: extraction time of 56.85 min, solid–liquid ratio of 1:56.71 g/mL and ethanol concentration of 44.64%, under which the actual yield of the total polyphenol crude extract (TPCE) reached 0.9985 ± 0.03%, which was highly consistent with the theoretical predicted value of 0.9960%, verifying the good fitting degree of the established model. Taking L-ascorbic acid as the positive control, the antioxidant activity of TPCE was evaluated by determining its scavenging capacity against ABTS·⁺, ·OH and DPPH· free radicals, and the half-maximal effective concentration (EC₅₀) values were measured to be 0.8850, 0.9490 and 4.198 mg/mL, respectively. With acarbose as the reference drug, the inhibitory effects of TPCE on α-amylase and α-glucosidase related to carbohydrate metabolism were assayed, and the corresponding half-maximal inhibitory concentration (IC₅₀) values were 0.0135 and 130.3 mg/mL, respectively. Furthermore, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was employed for the tentative identification of bioactive components in TPCE, and a total of 48 and 64 chemical constituents were characterized in negative and positive ion modes, respectively, providing a chemical basis for the biological activities of TPCE. This study confirmed that UAE is an efficient and feasible technology for extracting polyphenols from H. erinaceus, which lays a theoretical foundation for the development and utilization of its polyphenols, and also provides novel insights into the development of natural functional ingredients and potential therapeutic agents for the intervention of type 2 diabetes. Additionally, the findings further validate edible fungi as a valuable reservoir of natural bioactive substances, with promising application prospects in the research and development of functional foods and pharmaceuticals targeting metabolic diseases. Full article

Background/Objectives: Worldwide, diabetes is a 21st century disease with continuously increasing prevalence. Current medications often have long-term adverse effects, which is why new substances are needed to help combat these disadvantages. Methods: In this respect, the present study develops a series of compounds with potential antidiabetic activity, including synthesis, physicochemical–spectral characterization and in vitro–in silico evaluation. Results: The sulfonamide derivatives were obtained by condensation reactions of para-toluenesulfonamide (p-TSA) with two different isocyanates, directly or after the condensation reaction with urea. The spectroscopic methods, IR, ¹H-NMR, ¹³C-NMR, were used for the structural elucidation of the compounds to confirm the presence of the functional groups responsible for the antihyperglycemic action, namely amide, azomethine and sulfonyl groups. Cytotoxicity screening on NCTC fibroblasts confirmed the excellent safety profile of the most synthesized derivatives across the tested range (100–1500 μg/mL). In contrast, the p-TSA-c-d derivative showed a clear transition from a biocompatible profile at 100 μg/mL to a more cytotoxic phenotype at concentrations exceeding 750–1500 μg/mL. The synthesized derivatives, particularly p-TSA-c-d, exhibited remarkable antidiabetic potential by effectively inhibiting α-amylase and α-glucosidase, with IC₅₀ values as low as 46.54 μM, outperforming the standard reference acarbose. The molecular docking tests revealed different mechanisms for the inhibitory activity exerted by the p-TSA derivatives on the two targeted enzymes. Conclusions: Although these developed compounds can be considered promising antidiabetic agents, studies can be further deepened in the future by performing in vivo tests. Full article

The effects of static magnetic field (SMF) treatment on the solid-state culture of Sanghuangporus vaninii (SV) were investigated to enhance metabolite production and bioactivity. SMF parameters including intensity, exposure duration, and temperature were optimized, and treatment at 4 mT for 2 h per day produced the most pronounced effects, increasing total flavonoid (TFC), polyphenol (TPC), and triterpenoid (TTC) contents by 61–438% compared with the control. Ultrasonic extraction and semi-preparative chromatography enabled the isolation of three key compounds: D-(+)-trehalose (1), 5,7-dihydroxy-3,4′-dimethoxyflavone (2), and pinolenic acid (3), all of which were elevated following SMF treatment. Importantly, SMF exposure was associated with enhanced inhibitory activities against enzymes relevant to chronic metabolic disorders. The overall inhibitory activities against α-amylase, α-glucosidase, pancreatic lipase, and xanthine oxidase increased by 6–28% compared with the control, reaching a maximum inhibition of 97.60 ± 0.17%. Preliminary in vitro screening at 100 μg/mL showed that compounds 1 and 2 inhibited both α-amylase and α-glucosidase, whereas compound 3 selectively inhibited pancreatic lipase. Subsequent IC₅₀ analysis confirmed that compound 2 under SMF treatment exhibited inhibitory activity comparable to acarbose against α-amylase (45.62 μg/mL vs. 52.18 μg/mL) and α-glucosidase (38.74 μg/mL vs. 35.42 μg/mL). In addition, compound 3 showed moderate inhibition of pancreatic lipase with an IC₅₀ value of 42.15 μg/mL. These findings suggest that SMF treatment may enhance metabolite production and in vitro enzyme inhibitory activity in S. vaninii. However, these results are limited to in vitro assays, and further studies including cellular and in vivo validation, toxicity assessment, and pharmacokinetic evaluation, are required before any therapeutic or industrial applications can be considered. Full article

The present work set out to examine the antidiabetic capacity of Abelmoschus esculentus (okra) fruit extract through a combined experimental and computational framework. Enzyme inhibition assays were carried out against four metabolic targets, and IC₅₀ values stood at 7.66 ± 0.31 mg/mL for alpha-glucosidase, 5.21 ± 0.18 mg/mL for alpha-amylase, 2.11 ± 0.15 microg/mL for DPP-4, and 9.17 ± 0.54 mg/mL for pancreatic lipase. The extract showed moderate-to-weak activity relative to standard inhibitors acarbose, sitagliptin, and orlistat. Sixteen drug-like phytochemicals obtained from the IMPPAT 2.0 database were docked against the crystal structures of all four tested enzymes (PDB: 8CB1, 5E0F, 2ONC, 1LPB). Alpha-Carotene, Vitamin E, and Spiraeoside emerged as the top-ranked compounds across all targets, with alpha-Carotene recording the strongest binding affinity of −11.1 kcal/mol against pancreatic lipase, which was 4.2 kcal/mol more negative than the positive control orlistat (−6.9 kcal/mol). PLIP-based interaction profiling mapped out hydrogen bonds, hydrophobic contacts, pi-stacking, and salt bridges at the atomic level. Absorption, distribution, metabolism, and excretion (ADME) and toxicity screening of alpha-Carotene returned a favourable pharmacokinetic profile with predicted LD₅₀ of 1510 mg/kg (Class 4) and inactivity across most toxicity endpoints. A 100 ns molecular dynamics simulation of the pancreatic lipase-alpha–Carotene complex, alongside the orlistat control, showed stable root mean square deviation (RMSD) (0.15–0.22 nm), a consistent Rg (~1.97 nm), and sustained hydrogen bonding throughout the trajectory. Free-energy landscape analysis revealed a well-defined single energy basin for alpha-Carotene, suggesting a thermodynamically stable binding conformation. These findings lay the molecular basis for using okra phytochemicals as adjunctive agents in diabetes management, though in vivo validation remains necessary. Full article

By investigating the conditions for the C–C coupling reaction of p-terphenyls, we successfully synthesized C–C coupled dimeric p-terphenyls for the first time using a reaction system involving air, silica gel, and B(OH)₃. Additionally, we developed a novel method to synthesize furan-fused p-terphenyl dimers through solvent-free reactions by creatively applying rotary evaporation and heating. Compounds 6–12, 16, 20, and 22 demonstrated DPPH radical scavenging activity that was either stronger than or comparable to the positive control (vitamin C), with IC₅₀ values ranging from 0.14 to 4.61 μM. Compounds 4–22 also exhibited significant activity against α-glucosidase, with IC₅₀ values ranging from 0.37 to 17.9 μM, exceeding the efficacy of the positive control, acarbose. Moreover, compounds 6–14, 16–18, 21, and 22 demonstrated greater inhibitory activity against PTP1B compared with the positive control, oleanolic acid, with IC₅₀ values between 0.30 and 9.17 μM. These findings highlight their potential as promising leads or dietary supplements for the treatment and prevention of diabetes, as well as possible application as oxidative agents in food preservation. Full article

Background/Objectives: Loquat (Eriobotrya japonica) is widely cultivated for its fruit, while its aerial by-products remain largely underexploited despite increasing interest in plant-derived bioactive compounds and sustainable food systems. This study comprehensively investigates and compares the phenolic composition and in vitro bioactivities of loquat leaves and flowers to support their potential valorisation as functional ingredients. Methods: Extractable and non-extractable polyphenolic fractions were obtained and quantified, and the extractable fraction was further characterised using HPLC-ESI-QTOF-MS. In vitro bioactivity assessment included antioxidant capacity (FRAP and ABTS), glucose dialysis retardation index, and α-glucosidase inhibition. Results: Flowers contained significantly higher levels of both extractable and non-extractable polyphenols than leaves. Qualitative and semi-quantitative phenolic profiling, including multivariate analysis, revealed clear compositional differences between the two organs. Flowers showed a higher relative abundance of phenolic acids, as well as the presence of several compounds absent in leaves, such as kaempferol, naringenin-3-O-glucoside, and three glycosilated anthocyanins. Flower-derived fractions exhibited consistently higher antioxidant activity across all phenolic fractions than leaf-derived fractions, in agreement with their greater polyphenol content. Regarding antidiabetic activity, leaf samples showed a modest capacity to delay glucose diffusion, whereas this effect was not observed in flowers. In contrast, flower extracts displayed a strong inhibitory effect against α-glucosidase, exceeding that of the reference inhibitor acarbose, while this activity was not detectable in leaf extracts under the experimental conditions. Conclusions: These findings support the revalorisation of loquat by-products, particularly flowers, as sustainable sources of bioactive compounds with potential applications in functional foods and health-related products. Full article

Postprandial hyperglycemia represents a critical therapeutic target in type 2 diabetes mellitus (T2DM), requiring interventions that simultaneously address glycemic dysregulation and oxidative stress. This study evaluated the anti-hyperglycemic and antioxidant properties of Sclerocarya birrea leaf crude extract (CE) and biosynthesized silver nanoparticles (AgNPs). Phytochemical screening, nanoparticle characterization (UV–Vis, XRD, TEM, SEM, DLS, FTIR), enzyme inhibition assays (α-amylase, α-glucosidase, DPP-IV), glucose dynamics in Caco-2 cells, and antioxidant assays (DPPH, total antioxidant capacity, H₂O₂ cytoprotection) were performed. Phytochemical analysis identified flavonoids, tannins, alkaloids, and terpenoids as major constituents of Sclerocarya birrea leaf extract. AgNPs exhibited spherical morphology (36.8 ± 8.6 nm, n = 100 particles analyzed), face-centered cubic crystallinity (crystallite size: 32.1 nm), and characteristic surface plasmon resonance at 451 nm. Both formulations inhibited α-amylase (CE IC₅₀: 14 µg/mL; AgNPs IC₅₀: 14.07 µg/mL, n = 3) and α-glucosidase (CE IC₅₀: 15.96 µg/mL; AgNPs IC₅₀: 15.82 µg/mL, n = 3), showing substantial inhibition, though less potent than acarbose. Uniquely, AgNPs demonstrated selective DPP-IV inhibition (IC₅₀: 220.5 µg/mL, n = 3, p < 0.001 vs. CE), completely absent in CE. In antioxidant assays, DPPH scavenging potency was comparable between formulations (CE IC₅₀: 23.45 µg/mL; AgNPs IC₅₀: 22.26 µg/mL, n = 3), while CE achieved higher maximal scavenging at the tested concentrations. Conversely, AgNPs provided superior intracellular cytoprotection against H₂O₂-induced oxidative stress in kidney cells (80.2 ± 2.1% viability at 76 µg/mL vs. CE 69.8 ± 3.4% at 190 µg/mL, n = 3, p < 0.001), representing a 2.5-fold dose advantage. Neither formulation significantly altered glucose uptake or SGLT1 expression in intestinal epithelial cells (p > 0.05, two-way ANOVA, n = 3). These findings establish S. birrea-based formulations, particularly AgNPs, as promising multifunctional candidates for managing postprandial hyperglycemia and oxidative complications in T2DM. They also highlight nanotechnology-enhanced phytomedicine as an innovative therapeutic strategy. Full article

This study investigated the effect of solvent polarity on extraction yield, phytochemical composition, antioxidant activity, and α-amylase inhibition of Elaeagnus angustifolia L. leaf extracts to evaluate their antidiabetic potential. Extraction yields varied with solvent polarity, with the hydroethanolic extract showing the highest (18.00%) and n-hexane the lowest (0.05%) yield. The n-butanol and ethyl acetate fractions contained the most phenolics (309.05 and 290.97 mg GAE/g), ethyl acetate was the richest in flavonoids (102.11 mg QE/g), and tannins were concentrated in dichloromethane (66.24 mg CE/g). HPLC revealed solvent-specific profiles: rutin and gallic acid dominated in n-butanol, quercetin in ethyl acetate, and 4-hydroxybenzoic and ferulic acids in dichloromethane, while chicoric acid appeared in hydroethanolic and n-hexane extracts. Antioxidant assays (DPPH, ABTS, and FRAP) showed strong activity in polar extracts, particularly hydroethanolic and ethyl acetate fractions. The n-hexane extract exhibited the highest α-amylase inhibition (IC₅₀ = 36.70 µg/mL), surpassing acarbose (IC₅₀ = 126.14 µg/mL), while other fractions were inactive (IC₅₀ > 400 µg/mL). Molecular docking highlighted rutin, chlorogenic acid, and chicoric acid as potential enzyme binders. These findings demonstrate the chemical diversity and significant bioactivities of E. angustifolia leaves, supporting their potential as natural antidiabetic agents. Full article

Background/Objectives: This study aimed to evaluate the antidiabetic potential of five extracts/sub-extracts and five known cycloartane saponins [astragalosides (AST) I, II, III, IV, and cyclocanthoside E] from Astragalus noeanus (AN), using four specific diabetes-related molecular targets. Methods: Four diabetes-associated in vitro and in silico targets—protein tyrosine phosphatase 1B (PTP1B), dipeptidyl peptidase IV (DPP IV), α-amylase, and advanced glycation end-products (AGEs)—were employed to obtain comprehensive antidiabetic activity profiles. Additionally, the antioxidant and prebiotic capacities of the extracts/sub-extracts were assessed in vitro. A cycloartane saponin was isolated and structurally characterized. Quantitative analyses of total flavonoids, total saponins, and high-performance thin-layer chromatography (HPTLC) were performed to profile the chemical constituents of the plant material. Results: Among the extracts/sub-extracts, the aqueous extract (ANW) exhibited the highest inhibitory effects against all four diabetes-related targets, with inhibition percentages ranging from 83.70% to 93.49%. The methanol extract (ANM) demonstrated significant prebiotic activity comparable to standard controls on two Lactobacillus strains. The chloroform extract (ANC) showed the highest flavonoid content and exhibited the strongest antioxidant activity across all assays. ANM yielded the highest saponin content (3250 mg escin equivalent/g). HPTLC quantification revealed that AST IV was the predominant saponin in ANM (14.28 μg/mg) after cyclocanthoside E (117.27 ± 6.71 μg/mg). Among the saponins, AST IV displayed the most potent inhibition in diabetes-related enzyme assays, surpassing reference drugs acarbose and vildagliptin at equivalent concentrations. AST III also demonstrated considerable activity, ranking just below AST IV. Molecular docking studies identified AST II and AST III as the most promising ligands, exhibiting superior binding affinities and stronger hydrogen bonding and hydrophobic interactions with target proteins. Cyclocanthoside E was isolated from A. noeanus and evaluated for its antidiabetic effects for the first time, with its structure confirmed by NMR and LC-HRMS analyses. Conclusions: This study highlights Astragalus noeanus as a promising source for safe and effective antidiabetic agents. The potent activity of the aqueous extract, along with AST IV and AST III, warrants further investigation through clinical trials to validate their therapeutic potential in diabetes management. Full article

A novel series of benzothiazole scaffolds were presented to test their in vitro α-amylase and α-glucosidase activities for combating diabetes mellitus, which is one of the most rapidly growing diseases. The tested compounds were elucidated structurally by various spectroscopic techniques like ¹H NMR, ¹³C NMR and HRMS. All compounds exhibited a varied range of inhibitory activities against targeted α-amylase and α-glucosidase enzymes, with IC₅₀ values of 1.58 ± 1.20 to 7.54 ± 3.60 µM (α-amylase) and 2.10 ± 1.10 to 8.90 ± 4.10 (α-glucosidase), respectively. The obtained results were compared with the standard acarbose drug, with IC₅₀ values of 0.91 ± 0.20 µM (α-amylase) and 1.80 ± 1.10 µM (α-glucosidase). Specifically, methyl 2-amino-4-((6-methoxypyridin-3-yl)methoxy)benzo[d]thiazole-6-carboxylate (5c) and methyl 4-((6-methoxypyridin-3-yl)methoxy)-2-(thiazole-2-carboxamido)benzo[d]thiazole-6-carboxylate (6b) emerged as potent inhibitors of α-amylase and α-glucosidase enzymes. These potent compounds were further screened for in silico molecular docking studies to investigate possible binding interactions with active sites of targeted enzymes, and results obtained demonstrated that potent compounds exhibited stronger binding affinities toward anti-diabetic enzymes compared to the positive control acarbose. Full article

Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic metabolic diseases, and inhibition of α-glucosidase activity represents an effective therapeutic strategy. Chitin is the most abundant renewable polysaccharide in the ocean, with its monosaccharide being N-acetylglucosamine (NAG). To evaluate the potential of NAG glycosides as novel α-glucosidase inhibitors, three common phenolic compounds were modified via NAG glycosylation. Their inhibitory activities were assessed at both the enzymatic and cellular levels. In addition, density functional theory (DFT), molecular dynamics (MD) simulations, and molecular docking analyses were employed to systematically investigate the effects of NAG glycosylation on enzyme inhibition and the underlying mechanisms. Compared with the parent phenolic compounds, NAG glycosides exhibited significantly enhanced α-glucosidase inhibitory activity, with NAG introduction markedly improving their binding affinity to α-glucosidase. Among them, glycoside 3a displayed the optimal inhibitory effect, comparable to acarbose, and at the cellular level, its activity at high concentrations was comparable to or slightly higher than that of metformin. Circular dichroism (CD) and MD analyses indicated that glycoside 3a increased the conformational flexibility of key residues and enhanced the structural looseness of the enzyme, thereby inhibiting its activity. NAG glycosides constitute a promising class of marine-derived α-glucosidase inhibitors, warranting further structural optimization and rational design to enhance their activity and selectivity. Full article

Diabetes mellitus is a major global health concern associated with severe metabolic and cardiovascular complications. This study evaluated the antidiabetic and antioxidant activities of Oxalis corniculata L. aerial parts, with a focus on α-glucosidase and α-amylase inhibition, using a combination of in vitro assays and in silico analyses. Among the tested fractions, the ethyl acetate fraction exhibited the strongest inhibitory activity against both enzymes, with IC₅₀ values of 0.097 and 0.015 mg/mL for α-glucosidase and α-amylase, respectively, surpassing those of the reference drug, acarbose. This fraction also demonstrated potent antioxidant activity, with IC₅₀ values of 0.025 and 0.020 mg/mL in DPPH and ABTS assays, respectively. To elucidate the underlying mechanisms beyond digestive enzyme inhibition, bioactive constituents were screened and evaluated using network pharmacology, molecular docking, molecular dynamics simulations, and density functional theory (DFT) calculations. Molecular docking and dynamic simulations confirmed stable and energetically favorable interactions with α-glucosidase and α-amylase. Network pharmacology analysis revealed that the antidiabetic effects of O. corniculata involve modulation of insulin resistance-related pathways, particularly PI3K/Akt signaling, GLUT4 translocation, and inflammation-associated targets, alongside regulation of oxidative stress through redox-related enzymes. Complementary DFT analysis provided molecular-level insights into the antioxidant mechanisms, highlighting favorable electronic properties that support efficient radical scavenging. Overall, this integrated experimental–computational study provided valuable evidence of O. corniculata aerial parts as a promising multi-target phytotherapeutic candidate for diabetes management, extending its therapeutic relevance beyond α-glucosidase and α-amylase inhibition. Full article