The skipjack tuna (Katsuwonus pelamis) is one of the least commercially exploited tuna globally. The possible medicinal benefits of K. pelamis extract have not been explored. We investigated the 70% ethanol (EtOH) soluble fractions of skipjack tuna heart for the inhibition of protein-tyrosine phosphatase 1B (PTP1B) and α-glucosidase. The dichloromethane (CH2Cl2) fraction significantly inhibited the activities of PTP1B and α-glucosidase. Repeated column chromatography of the active CH2Cl2 fraction based on bioactivity-guided fractionation yielded cholesterol, cholesteryl myristate, and sn-1,3-dipalmitoyl-2-oleoylglycerol; the latter significantly inhibited PTP1B and α-glucosidase. Kinetic study revealed that sn-1,3-dipalmitoyl-2-oleoylglycerol showed mixed-type inhibition against PTP1B. Docking simulations showed that sn-1,3-dipalmitoyl-2-oleoylglycerol selectively inhibited PTP1B and α-glucosidase by targeting its active site and exhibited good binding affinity, with a docking score of -7.4 and -7.1 kcal/mol, respectively. Moreover, 70% EtOH, CH2Cl2 and EtOAc fractions, and sn-1,3-dipalmitoyl-2-oleoyl glycerol significantly inhibited ONOO-mediated albumin nitration. These results implicate tuna heart extract as a potential functional food ingredient for the prevention and treatment of diabetes and its associated complications.

Persicaria odorata (Lour.) contains considerable amounts of phytochemicals, including phenolics and essential oils, which have been reported to inhibit α-glucosidase activity. However, which bioactive compounds play a key role in inhibiting the α-glucosidase activity is unclear. To address this issue, the methanolic extract of P. odorata was assayed via in vitro studies, and forty-four compounds in P. odorata extracts were elucidated using in silico studies. The extract strongly inhibited yeast α-glucosidase with an IC50 value of 0.31 µg/mL, which was 450-fold more potent than acarbose (IC50 = 139.47 µg/mL), under experimental conditions. The Lineweaver-Burk plots indicated that the inhibition type of the extract on α-glucosidase is a noncompetitive inhibitor. Molecular docking demonstrated that procyanidin B (P9) and rutin (P19), which belong to the flavonoids, were predicted by computational approaches to be bioactive compounds that have more favorable binding interactions to yeast α-glucosidase residues compared to forty-four other compounds and acarbose. Molecular dynamics simulations revealed that P9 and P19 complexes with yeast α-glucosidase remained stable during the 500 ns simulations. Moreover, both P9 and P19 were predicted to qualify as α-glucosidase inhibitors with low toxicity. These findings suggest that P. odorata could be used as an alternative edible plant to manage postprandial hyperglycemia in T2DM, and could serve as basic scientific data. Further experimental studies of the pure bioactive compounds are necessary to support these findings.

Silybum marianum (SM) is a rich source of flavonolignans with promising antioxidant and antidiabetic properties; however, its therapeutic application is limited by poor stability and bioavailability. This study combined experimental and computational approaches to develop and evaluate SM-loaded chitosan nanoparticles (CS-SM nanoparticles). Microwave-assisted extraction followed by LC-MS/MS profiling identified eleven metabolites, including major flavonolignans characteristic of SM. Nanoparticles prepared by ionic gelation exhibited favorable physicochemical properties, including a particle size of 173-189 nm, a polydispersity index of 0.23, a zeta potential of +41.5 mV, an encapsulation efficiency of 98%, and a drug loading capacity of 50%, indicating the formation of a stable colloidal delivery system. CS-SM nanoparticles showed enhanced antioxidant, anti-inflammatory, and α-amylase inhibitory activities compared with crude extracts. The formulation exhibited an α-amylase IC50 value of approximately 0.40 mg/mL and maintained low hemolytic activity, suggesting favorable preliminary biocompatibility. Molecular docking demonstrated favorable interactions of neosilyhermin A, silibinin, and silyhermin with α-amylase and α-glucosidase active sites. Short-timescale molecular dynamics simulations revealed ligand-dependent behavior within the chitosan-TPP matrix, indicating different release tendencies among the investigated flavonolignans. Overall, the results support CS-SM nanoparticles as a promising platform for the delivery of bioactive phytochemicals with antioxidant and antidiabetic potential.

In this study, due to the side effect profiles and low efficacy of currently used inhibitors, novel benzimidazole-oxadiazole derivatives (6a-6e, 7a-7e) were synthesized as dual inhibitors of α-GLY and AR. Their structures were elucidated using [13]C-NMR and [1]H-NMR techniques. Their binding properties were investigated by molecular docking studies, and their ADME properties were screened in silico. AR and α-GLY inhibitory effects of the synthesized compounds were examined. The compounds were observed to exhibit partially similar inhibitory effects to the reference drug epalrestate (IC50: 0.78 nM; KI: 0.74 ± 0.0 nM) on AR inhibition. Among them, compounds 6a, 6b, and 6c showed the highest activity with KI values of 8.6 ± 0.4, 3.5 ± 0.3 and 6.3 ± 0.5 nM, respectively. Compounds 6a and 7e were found to have higher inhibitory activity against the α-GLY enzyme than the reference drug Acarbose (IC50: 128.4 µM; KI: 96.2 ± 5.7 µM) with KI values of 5.8 ± 0.4 and 7.9 ± 0.8 µM, respectively. Overall, the newly synthesized compounds demonstrated pronounced AR inhibitory activity and notable α-GLY inhibition. Nevertheless, further pharmacological and toxicity evaluations are required to confirm their therapeutic potential. Among the tested molecules, compounds 6a and 7e may therefore be considered potential candidates for further investigation as anti-diabetic agents.

Digestive enzymes such as pancreatic lipase (PL), α-glucosidase (AG), and α-amylase (AA) play key roles in the hydrolysis of dietary lipids and carbohydrates and are therefore relevant biochemical targets for evaluating compounds with potential to modulate postprandial metabolic responses. Neurolaena lobata (L.) R. Br. ex Cass. (Asteraceae) is a neotropical medicinal species traditionally used for several health-related conditions, including metabolic complaints. This study evaluated the in vitro inhibitory activity of the hydroalcoholic extract, selected VLC fractions, and isolated metabolites from N. lobata leaves against PL, AG, and AA. Enzyme inhibition screening of the extract and VLC fractions was used to select fractions for phytochemical investigation, affording six known metabolites: the sesquiterpene lactones neurolenin B (C1) and lobatin A (C2), the benzoic acid derivatives p-hydroxybenzoic acid (C3) and 3,4-dihydroxybenzoic acid (C4), and the flavonoids 6-hydroxykaempferol 3,7-dimethyl ether (C5) and quercetagetin 3,7-dimethyl ether (C6). The hydroalcoholic extract and the MeOAc and iPrOH fractions inhibited PL, AG, and AA. Among the isolated compounds, C1, C2, C5 and C6 inhibited PL and AG, with IC50 values ranging from 134 to 615 µM and from 170 to 639 µM, respectively, whereas all compounds showed weak AA inhibition. Exploratory kinetic analysis yielded apparent inhibition profiles mainly consistent with competitive behavior; C6 showed an apparent profile consistent with noncompetitive inhibition against AG under the assay conditions used. These findings expand the phytochemical and in vitro bioactivity profile of N. lobata and provide preliminary evidence of digestive enzyme modulation in isolated enzyme systems, without establishing therapeutic efficacy.

Agricultural and horticultural by-products represent an underexploited source of valuable bioactive compounds that can contribute to the development of more sustainable production systems. This study investigated the chemical composition and biological activities of the essential oil obtained from the horticultural byproducts of Artemisia dracunculus. The waste aerial biomass was subjected to steam distillation, and the essential oil was characterized by gas chromatography-mass spectrometry. Its antioxidant, α-amylase and α-glucosidase inhibitory, phytotoxic, antibacterial, and antibiofilm activities were subsequently evaluated. The essential oil was characterized as an estragole-rich chemotype (70.17%), with trans-β-ocimene and cis-β-ocimene as other main constituents. The essential oil showed moderate antioxidant activity and measurable enzyme inhibitory activity and, despite showing limited effects on seed germination, it significantly inhibited radical elongation in selected plant species. Furthermore, it demonstrated excellent antibiofilm activity, significantly reducing the metabolic activity of mature cells of bacteria associated with biofilm formation: Listeria monocytogenes, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae and Staphylococcus aureus. The results demonstrate how horticultural by-products from A. dracunculus maintain a chemical profile comparable to conventional plant material and represent a valuable source of bioactive compounds with promising potential for sustainable agri-food applications.

α-Glucosidase inhibitors (AGIs) significantly regulate blood glucose by delaying carbohydrate digestion and slowing glucose absorption, thus playing a critical role in glycemic control. Structurally, dihydromyricetin (Unless otherwise stated, the term dihydromyricetin used throughout this manuscript refers to trans-(2R,3R)-(+)-dihydromyricetin.) differs from myricetin in that the C2=C3 double bond in the C-ring is saturated, resulting in a dihydroflavonol instead of a flavonol. This study investigated the inhibition mechanism of α-glucosidase by the C2=C3 double bond structure using a set of integrated and multi-perspective approaches combining enzyme kinetics, multi-spectroscopic methods, molecular docking, isothermal titration calorimetry (ITC), and surface plasmon resonance (SPR). Myricetin (IC50 = 13.648 ± 0.157 μM) was found to be a more potent α-glucosidase inhibitor than dihydromyricetin (IC50 = 453.922 ± 1.643 μM). Enzyme kinetics indicated that myricetin acted as a competitive inhibitor, whereas dihydromyricetin functioned as a non-competitive inhibitor. To further examine these interactions, multi-spectroscopic analysis demonstrated that binding of myricetin caused significant changes in the microenvironment around fluorescent amino acids (such as tyrosine and tryptophan) in α-glucosidase, resulting in slight unfolding of the enzyme structure. Additionally, molecular docking provided a detailed molecular perspective, identifying hydrogen bonding and hydrophobic interactions as the primary forces driving the binding of two flavonoids to α-glucosidase. Delving deeper into the binding mechanism, ITC analysis provided thermodynamic evidence that myricetin (KD = 6.215 ± 0.022 μM) exhibited a stronger binding affinity to α-glucosidase than dihydromyricetin (KD = 232.648 ± 1.236 μM), with both interactions being enthalpy-driven and primarily mediated by hydrogen bonds. Building on this, SPR analysis offered additional insights into the binding process, showing that myricetin not only had a higher binding affinity (KD = 3.416 ± 0.015 μM) but also a faster association rate (ka = 1668 ± 23 M[-1] s[-1]) compared to dihydromyricetin (KD = 11.539 ± 0.056 μM, ka = 339.7 ± 17.1 M[-1] s[-1]). In conclusion, this study demonstrated that the C2=C3 double bond plays a key role in enhancing α-glucosidase/inhibitor interactions, providing a theoretical basis for the design of novel AGIs and proposing a new set of multi-perspective methods for elucidating these inhibition mechanisms.

Inhibiting α-glucosidase (AG) enzyme is recognized as a key therapeutic approach for diabetes treatment. Nine saturated anacardic acid derivatives (2-10) were synthesized, well-characterized, and evaluated for their inhibitory activity against AG. All six sulfonylhydrazide saturated anacardic acid analogues (5-10) were disclosed as novel compounds, and their structures were endorsed by NMR spectroscopy, X-ray crystallography, and mass spectrometry. They exhibited strong inhibition against AG with IC50 in a range of 0.24-6.01 µM, significantly surpassing the reference antidiabetic drug acarbose (IC50 = 817.38 µM). Notably, 10 was found to be a potent α-glucosidase inhibitor with an IC50 of 0.24 µM. The strong inhibitory effect of the side chain against AG was demonstrated through a comparison between 10 and a structurally similar salicylic acid analogue. Kinetic studies revealed that 10 functioned as a competitive inhibitor, binding to the free enzyme with an equilibrium constant Ki = 0.96 µM. Molecular docking studies further strengthened that compound 10 predominantly binds to the orthosteric site of AG with strong binding affinity and multiple stabilizing interactions, supporting its superior inhibitory activity compared to its precursor, the saturated anacardic acid 2. These findings contribute to the development of potent therapeutic agents for diabetes treatment.

Bioactive peptides are emerging functional ingredients for attenuating postprandial glycemia through the inhibition of carbohydrate-digesting enzymes. This study characterized the synthetically produced oat-derived octapeptide LQAFEPLR (LQ8) and its cyclized variant CLQAFEPLRC (CLQ8), and evaluated their α-glucosidase inhibitory properties and food application potential. Results revealed that both short peptides were highly soluble, thermally stable, and predicted to be non-toxic, although potential allergenicity was suggested based on sequence homology with oat proteins and warrants further validation. At a relatively low concentration (3.1 μg/mL), LQ8 and CLQ8 exhibited α-glucosidase inhibition of 26.4% and 25.0%, respectively. However, the weak dose-response relationship and kinetic observations suggested different inhibitory behaviors, with LQ8 showing a mixed or uncompetitive-like mode and CLQ8 displaying a non-classical modulatory effect against yeast maltase α-glucosidase. These differences may be related to their distinct binding profiles, as docking suggested that the peptides interacted with catalytic or near-catalytic residues through partial or alternative binding modes rather than fully occupying the catalytic pocket. When incorporated into biscuits, both peptides remained bioactive after baking at 160 °C, with biscuit digesta showing α-glucosidase inhibition of 39.3% for LQ8 and 46.9% for CLQ8. Furthermore, both peptides significantly reduced in vitro starch digestibility, as indicated by significantly lower incremental area under curve values for d-glucose release during simulated gastrointestinal digestion compared with the control biscuit. These findings suggest the potential of both peptides as non-toxic, thermally stable, α-glucosidase inhibitory ingredients for incorporation into bakery products aiming to attenuate postprandial glycemic responses.

The ethanol extract of H. capitata stems and flowers were prepared using the hot extraction method with 96% ethanol for chemical composition and biological analysis. GC-MS and LC-MS identified 71 compounds across both extracts. The flower extract contained the highest total phenolic content (TPC) (48.47 ± 2.03 mg GAE/g), while the stem extract showed higher total flavonoid content (TFC) (9.21 ± 0.10 mg QE/g), and total triterpenoid contents (TTC) (27.01 ± 1.06 mg OAE/g). The flower extract demonstrated stronger antioxidant activity than the stem extract, with IC50 values of 18.00 ± 0.28 µg/mL (DPPH) and 3.81 ± 0.04 µg/mL (ABTS). It also exhibited antifungal activity against four pathogenic fungal strains (MIC: 500-1000 µg/mL). In addition, both extracts showed α-glucosidase inhibitory activity, particularly the flower extract (IC50 = 5.87 ± 0.18 µg/mL), compared with the stem extract (IC50 = 23.27 ± 0.77 µg/mL), suggesting the presence of constituents associated with antidiabetic potential. Molecular docking suggested that key compounds-1,2-cyclohexanedicarboxylic acid bis(2-ethylhexyl) ester (stem) and 6β-acetoxy-5-epilimonin (flower)-may contribute to enzyme inhibition, with binding energies of -10.0 and -9.4 kcal/mol, respectively. Overall, these findings suggest that H. capitata, particularly its flowers, represents a promising source of bioactive compounds for further isolation and in vivo validation.

To discover novel potential enzyme inhibitors based on natural products, a series of N-acyl pregnane alkaloid ester derivatives were designed, synthesized, and evaluated for their inhibitory activity against acetylcholinesterase (AChE) and α-glucosidase. The bioassay test results revealed that the target compounds generally showed more potent inhibition against α-glucosidase than against AChE. Notably, compounds 6e and 6i demonstrated significant α-glucosidase inhibitory activity, with IC50 values of 29.85 µM and 38.11 µM (acarbose IC50: 16.49 µM), respectively, and exhibited low cytotoxicity toward Thle-2 cells, with IC50 values of 112.70 µM and 73.65 µM, respectively. Structure-activity relationship (SAR) analysis indicated that derivatives bearing an N-tigloyl group and nitro or pyridine substituents at the C-20 position contributed to enhanced α-glucosidase inhibition. Enzyme kinetics confirmed that 6e and 6i function as reversible, noncompetitive inhibitors of α-glucosidase. Molecular docking studies further illustrated that both compounds bind to the lateral surface of the α‑glucosidase through hydrogen bonds and hydrophobic interactions, rather than occupying the catalytic active site. These findings highlight that 6e and 6i exhibit certain inhibitory activity, providing a basis for the design of subsequent derivatives.

Diabetes mellitus caused 3.4 million deaths in 2024. Although α-glucosidase and DPP-IV inhibitors are utilised therapeutically, synthetic drugs cause side effects. Durio kutejensis was examined for antihyperglycemic potential. This study assessed the antihyperglycemic activity of the leaves and bark of D. kutejensis from four Kalimantan provinces and identified active compounds through untargeted metabolomic analysis. Ethanol extracts were tested for in vitro α-glucosidase and DPP-IV inhibitory activities, confirmed through in vivo, and followed by untargeted metabolomic via UHPLC-Q-Orbitrap-HRMS. Bark extracts suppressed α-glucosidase activity with IC50 values ranging from 1.65 to 15.10 µg/mL. A total of 44 metabolites were putatively identified; 12 were linked to α-glucosidase inhibition. In vivo, East Kalimantan bark extract (KT2) significantly improved glycemic control (p < 0.05), with a reduction in blood glucose of 24 mg/dL. These findings reinforce the therapeutic value of D. kutejensis bark as an antihyperglycemic agent.