Search Results (225)

This study describes the synthesis of heterocyclic derivatives containing multiple nitrogen atoms serving as important moieties for developing novel antidiabetics through a simple synthetic pathway. We herein describe the synthesis and characterization of novel pyrimidine derivatives using one-pot reactions in a catalyst-free and efficient manner through a two-stage process involving the synthesis of 2-amino-4-hydrazinyl-6-methoxy pyrimidine, followed by a reaction with phenyl isothiocyanate derivatives. The structures of all the new compounds were confirmed via physical and spectral analysis. Furthermore, we evaluated the synthesized pyrimidine derivatives’ biological activities in relation to their potential roles as novel anti-diabetic agents by testing their activity profiles against the enzymes α-glucosidase and α-amylase. Compound 4 expressed the highest level of activity against α-glucosidase and α-amylase, with a greater inhibitory concentration (IC₅₀ of 12.16 ± 0.12 µM and IC₅₀ 11.13 ± 0.12 µM) compared to that of acarbose (IC₅₀ = 10.60 ± 0.17 µM and IC₅₀ = 11.30 ± 0.12 µM), which is widely used as a standard antidiabetic drug. The primary structure activity relationship analysis identified the impact of an electron- withdrawing group, especially with respect to fluorine on inhibitory activity. This was further confirmed in molecular docking studies, which demonstrated that both compounds exhibited similar inhibition patterns and emphasized the significance of incorporating a lipophilic electron-withdrawing substituent on the phenyl ring, along with the 2,4-diaminopyrimidine scaffold. Full article

The current study investigates the chemical profiling, antioxidant activities, and enzyme inhibitory and cytotoxic potential of the water and methanolic extracts of different parts (flower, leaf, and bulb) of Muscari armeniacum. Chemical profiling was performed using UHPLC-MS/MS. At the same time, different in vitro assays were employed to support the results for antioxidant potential, such as DPPH, ABTS, FRAP, CUPRAC, metal chelation, and PBD, along with the measurement of total phenolic and flavonoid contents. Enzyme inhibition was investigated for cholinesterase (AChE and BChE), α-amylase, α-glucosidase, and tyrosinase enzymes. Additionally, the relative expression of NRF2, HMOX1, and YGS was evaluated by qPCR. LC-MS/MS analysis indicated the presence of some significant compounds, including apigenin, muscaroside, hyacinthacine A, B, and C, and luteolin. According to the results, the highest TPC and TFC were obtained with both extracts of the leaves, followed by the water extract (flower) and methanolic extract of the bulb. In contrast, the methanolic extract from the bulb exhibited the highest antioxidant potential using DPPH, ABTS, CUPRAC, and FRAP, followed by the extracts of leaves. In contrast, the leaf extracts had the highest values for the PBD assay and maximum chelation ability compared to other tested extracts. According to the enzyme inhibition studies, the methanolic extract from the bulb appeared to be the most potent inhibitor for all the tested enzymes, with the highest values obtained for AChE (1.96 ± 0.05), BChE (2.19 ± 0.33), α-amylase (0.56 ± 0.02), α-glucosidase (2.32 ± 0.01), and tyrosinase (57.19 ± 0.87). Interestingly, the water extract from the bulb did not inhibit most of the tested enzymes. The relative expression of NRF2 based on qPCR analysis was considerably greater in the flower methanol extract compared to the other extracts (p < 0.05). The relative expression of HMOX1 was stable in all the extracts, whereas YGS expression remained stable in all the treatments and had no statistical differences. The current results indicate that the components of M. armeniacum (leaves, flowers, and bulb) may be a useful source of natural bioactive compounds that are effective against oxidative stress-related conditions, including hyperglycemia, skin disorders, and neurodegenerative diseases. Complementary in silico approaches, including molecular docking, dynamics simulations, and transcription factor (TF) network analysis for NFE2L2, supported the experimental findings and suggested possible multi-target interactions for the selected compounds. Full article

Although α-amylase is crucial for postprandial glucose control, existing inhibitors present various side effects, necessitating the exploration of natural alternatives. The ability of sugarcane polyphenol (SP) to inhibit α-amylase remains unclear. This study assessed the inhibitory activity of SP via in vitro assays, circular dichroism (CD), fluorescence quenching, and stability analysis, while the mechanism of action was elucidated using molecular docking and molecular dynamics (MD). The results showed that the IC₅₀ of the SP was 0.841 ± 0.029 mg/mL, with proanthocyanidin-B1 (PC-B1) presenting the most potent effect (IC₅₀ = 0.504 ± 0.019 mg/mL). CD and barycentric mean (BCM) analysis indicated that the complexes might limit substrate binding. The mechanistic assessment showed that the polyphenols bonded to the active enzyme pockets to form stable complexes with reduced key residue fluctuations. In conclusion, SP, especially PC-B1, effectively inhibited α-amylase activity via structural regulation and molecular interactions, providing a theoretical basis for developing natural hypoglycemic agents. Full article

Natural deep eutectic solvents (NADESs) have emerged as a promising eco-friendly alternative to petrochemicals for extracting plant metabolites. Considering that the demand for sustainable “green” ingredients for industrial applications is growing, those solvents are purported to develop extracts with interesting phytochemical fingerprints and biological activities. Given the interest in flavonoids from Chenopodium quinoa Willd. leaves, an efficient “green” extraction method was developed by investigating eight NADESs with defined molar ratios, i.e., malic acid-choline chloride (chcl)-water (w) (1:1:2, N1), chcl-glucose-w (5:2:5, N2), proline-malic acid-w (1:1:3, N3), glucose-fructose-sucrose-w (1:1:1:11, N4), 1,2-propanediol-chcl-w (1:1:1, N5), lactic acid-glucose-w (5:1:3, N6), glycerol-chcl-w (2:1:1, N7), and xylitol-chcl-w (1:2:3, N8). Rheological measurements of all NADESs confirmed their pseudoplastic behaviors. To improve the extraction processes, differential scanning calorimetry (DSC) allowed us to determine the maximum amount of water that could be added to the most stable NADES (N1, N2, N3, and N4; 17.5%, 20%, 10%, and 10% w/w, respectively) to lower their viscosities without disturbing their eutectic environments. The phytochemical compositions of NADES extracts were analyzed using high-performance thin-layer chromatography (HPTLC), and their free radical scavenging and α-amylase inhibitory properties were assessed using HPTLC-bioautography. N2, diluted with 20% of water, and N7 presented the best potential for replacing methanol for an eco-friendly extraction of flavonoids, radical scavengers, and α-amylase inhibitors from quinoa leaves. Their biological properties, combined with a good understanding of both thermal behavior and viscosity, make the obtained quinoa leaf NADES extracts good candidates for direct incorporation in nutraceutical formulations. Full article

Obesity is a global health concern that elevates the risk of noncommunicable diseases (NCDs) such as type 2 diabetes, cardiovascular disease, and certain cancers. Phaseolus vulgaris (white bean) contains α-amylase inhibitors (αAIs) that can reduce carbohydrate digestion and absorption, potentially mitigating obesity and metabolic syndrome. This study investigated the impact of P. vulgaris extract (PVE) on obese rats. Male Wistar rats were fed either a standard diet (SD) or a cafeteria diet (CAF) for 17 weeks to induce obesity. Subsequently, rats in each dietary group were randomly assigned to receive a vehicle, low-dose PVE (200 mg/kg), high-dose PVE (300 mg/kg), or metformin (200 mg/kg) via an oral gavage for 6 weeks. The CAF group exhibited significantly greater weight gain compared to the SD group. In the CAF group, a low dose of PVE lowered postprandial glycemia during an oral glucose tolerance test (OGTT) at 60 and 120 min and decreased food and energy intake during weeks 17–20 and 18–19, respectively. In the SD group, a high dose of PVE reduced glycemia at 90 min in the OGTT, as well as body weight gain, food intake, and energy intake during week 17. However, the overall areas under the glucose curves in the OGTT were not significantly different across treatment groups (p > 0.05), and while individual time points showed changes, the overall glucose exposure (AUC) was not significantly altered. In conclusion, the αAIs present in P. vulgaris demonstrate the potential to reduce body weight, weight gain, glycemia, total cholesterol, and triglycerides in vivo, but in the CAF group, neither PVE dose significantly altered the TC or TG. This study provides strong support for further exploring Phaseolus vulgaris extract as a valuable functional ingredient in the food industry, particularly for developing products that aid in weight management and glycemic control. Full article

Global wheat and maize production, which reached two billion tonnes in 2021, generates significant agricultural waste with largely untapped potential. This study investigates the bioactive properties of ethanol extracts from wheat and maize harvest residues, their ethyl acetate fractions, and their principal compounds. In vitro assays (DPPH, ABTS, FRAP, and TRC) revealed variable antioxidant capacities among the samples, with ferulic acid demonstrating the strongest free-radical scavenging and reducing effects, often surpassing those of standard antioxidant controls. Enzyme inhibition assays identified the flavonoid tricin as the most effective inhibitor of α-glucosidase, acetylcholinesterase, and butyrylcholinesterase, while the flavonolignan mixture of salcolins A and B showed the highest inhibitory activity against α-amylase and tyrosinase. Antimicrobial testing using the broth microdilution method resulted in minimum inhibitory concentrations (MICs) ranging from 31.25 µg/mL to >1000 µg/mL. Gram-positive bacteria showed the highest susceptibility, Candida albicans exhibited variable sensitivity, and Gram-negative bacteria were resistant in the tested concentration range. Bioactivity increased in the order of extracts, fractions, and then individual compounds. These findings suggest that wheat and maize residues possess notable bioactive properties, highlighting their potential as sources of valuable and pharmacologically active compounds. Full article

Hypertension, type 2 diabetes (T2D), and obesity raise an individual’s risk of suffering from diseases associated with metabolic syndrome (MS). In humans, enzymes that play a role in the prevention and development of MS include angiotensin converting enzyme (ACE-1) associated with hypertension, α-amylase associated with T2D, and lipase linked to the development of obesity. Seaweeds are a rich source of bioactives consisting of proteins/peptides, polysaccharides, and lipids. This study examined the potential of seaweed-derived bioactives from Alaria esculenta, Ulva lactuca, and Palmaria palmata as inhibitors of ACE-1, α-amylase, and lipase. In vitro enzyme inhibitory assays were used to quantify the bioactivity of the seaweed extracts and compare their half-maximal inhibitory (IC₅₀) values to recognised positive control enzyme inhibitory drugs captopril© (an ACE-1 inhibitor), acarbose (an α-amylase inhibitor), and orlistat (a lipase inhibitor). Three seaweed extracts displayed enzyme inhibitory activities equal to, or more effective than, the reference positive control drugs. These were P. palmata peptides (ACE-1 IC₅₀ 94.29 ± 3.07 µg/mL, vs. captopril© 91.83 ± 2.68 µg/mL); A. esculenta polyphenol extract (α-amylase IC₅₀ 147.04 ± 9.72 µg/mL vs. acarbose 185.67 ± 12.48 µg/mL, and lipase IC₅₀ 106.21 ± 6.53 µg/mL vs. orlistat 139.74 ± 9.33 µg/mL); and U. lactuca polysaccharide extract (α-amylase IC₅₀ 168.06 ± 10.53 µg/mL vs. acarbose 185.67 ± 12.48 µg/mL). Proximate analysis also revealed that all three seaweeds were a good source of protein, fibre, and polyunsaturated essential fatty acids (PUFAs). These findings highlight the potential of these seaweeds in the management of diseases associated with MS and as foods. Full article

The present study aimed to qualitatively assess the influence of Chenopodium quinoa Willd. varieties (INIAP-Tunkahuan, INIAP-Pata de Venado varieties and Chimborazo genotype), phenological stages (40, 60, and 80 days), and places of cultivation (Pichincha and Chimborazo Ecuadorian provinces) on the leaf and seed phenolic composition and biological properties. Their nutraceutical potential was assessed through qualitative analyses of (i) their polyphenols by high-performance thin-layer chromatography (HPTLC); and (ii) their free radical scavenging (quenching of 2,2-diphenyl-1-picrylhydrazyl free radical, DPPH^•) and α-amylase inhibitory properties (iodine visualization of starch hydrolysis) by HPTLC–bioautography. Compared to seeds, the quinoa leaf methanolic extracts present a high content of polyphenols with free radical scavenging activity, and compounds with an α-amylase inhibitory property; both biological activities indicate a remarkable potential of quinoa leaves, which may be relevant for the treatment of diabetes but also for the chemoprevention and/or treatment of pathologies related to oxidative stress. In quinoa leaves harvested after 80 days of cultivation, regardless of the place of production and the variety, a high content of bioactive compounds was observed. Future research is undoubtedly needed to further promote quinoa leaves as a dietary vegetable or to develop them into a nutritional supplement. This would empower quinoa smallholders in Andean regions to promote the sustainable development of this culture in its places of origin. Full article

The increase in the incidence of hyperglycemia and diabetes poses the challenge of finding cost-effective natural inhibitors of starch digestion enzymes. Among natural compounds, phenolics have been considered as promising candidates. The aims of this study were as follows: (a) to investigate the effectiveness of the inhibition of different winemaking byproducts towards intestinal brush border α-glucosidase and pancreatic α-amylase in vitro; (b) to calculate an efficacy index relative to the standard acarbose for the phenolic pool of winemaking byproducts, as well as for isolated phenolic compounds and for the phenolic pools of different plants studied in the literature, in order to rank winemaking byproducts with respect to the reference drug and other natural alternatives. Among winemaking byproducts, red grape skins showed the highest inhibitory activities towards both α-glucosidase and α-amylase, which were, on average, 4.9 and 2.6 µg acarbose equivalents/µg total phenolics (µg Ac eq/µg GAE), respectively. A correlation was observed between the total phenolic contents of red grape skins and their inhibitory effectiveness, which is useful for standardizing the efficacy of phenolic extracts obtained from different winemaking processes. In general, the inhibitory activity of the phenolic pool of grape skins was higher than those of isolated phenolic compounds, namely anthocyanins and monomeric and polymeric flavanols and flavonols, probably due to synergistic effects among compounds. Hence, bioactive phenolic fractions could be produced with the focus on functionality rather than purity, in line with the principles of sustainable processing. Based on the efficacy index developed to compare different phenolic compounds and phenolic-rich plants studied in the literature as starch digestion enzyme inhibitors, red grape skins proved to be cost-effective candidates. Full article

In search of novel antidiabetic agents, we synthesized a new series of chalcones with benzimidazole scaffolds by an efficient ‘one-pot’ nitro reductive cyclization method and evaluated their α-glucosidase and α-amylase inhibition studies. The ‘one-pot’ nitro reductive cyclization method offered a simple route for the preparation of benzimidazoles with excellent yield and higher purity compared to the other conventional acid- or base-catalyzed cyclization methods. ¹H, ¹³C NMR, IR, and mass spectrum data were used to characterize the compounds. Single-crystal XRD data confirmed the 3D structure of compound 7c, which was crystalized in the P$\overline{1}$ space group of the triclinic crystal system. Hirshfeld surface analysis validates the presence of O-H..O, O-H…N, and C-H…O intermolecular hydrogen bonds. From the DFT calculations, the energy gap between the frontier molecular orbitals in 7c was found to be 3.791 eV. From the series, compound 7l emerged as a potent antidiabetic agent with IC₅₀ = 22.45 ± 0.36 µg/mL and 20.47 ± 0.60 µg/mL against α-glucosidase and α-amylase enzymes, respectively. The in silico molecular docking studies revealed that compound 7l has strong binding interactions with α-glucosidase and α-amylase proteins. Molecular dynamics studies also revealed the stability of compound 7l with α-glucosidase and α-amylase proteins. Full article

This work aimed to propose the reuse of processing waste from the Sicilian almond (Prunus amygdalus Batsch.) cultivar Tuono for the formulation of a new functional baked product (muffin) that is gluten- and lactose-free. Muffins were prepared using orange juice, rice flour, extra virgin olive oil, and enriched almond skin (3% and 6% w/w). The chemical-physical parameters, total phenols, and flavonoids (TPC and TFC), as well as the biological properties of the ingredients and muffins, were evaluated. Sensory analyses were also conducted. DPPH, ABTS, β-carotene bleaching, and FRAP tests were applied to measure the antioxidant potential. Muffin extracts were also tested against α-amylase and α-glucosidase enzymes. Muffins enriched with 6% almond skin (M6) showed the highest TPC and TFC with values of 26.96 mg gallic acid equivalent (GAE)/g and 24.12 mg quercetin equivalent (QE)/g, respectively. M6 exerted a promising antioxidant activity as an inhibitor of lipid peroxidation, with an IC₅₀ of 15.44 μg/mL at 30 min incubation. Moreover, muffin M6 showed a promising α-glucosidase inhibitory effect (IC₅₀ of 51.82 μg/mL). Based on the obtained results and supported by sensory analysis, muffins enriched with almond skin should be proposed as a promising example of upcycling for the development of a new functional bakery product. Full article

The inhibition of the alpha-amylase digestive enzyme impedes starch digestion by blocking access to the active site of the enzyme, thereby playing a role in the prevention of obesity and type 2 diabetes. Plant-derived alpha-amylase inhibitors (αAIs) are promising nonpharmacological alternatives for the prevention of these diseases. Alpha-amylase inhibitor-1 (αAI-1) present in common bean (Phaseolus vulgaris) is derived from a precursor protein. In this study, the effect of digestion on the digestibility, immune reactivity, and bioactivity of αAI-1 was assessed from four varieties of Hungarian common bean (Phaseolus vulgaris), with special regard to the precursor protein. For this purpose, αAI-1 was tested in both matrix (native flour and cooked flour) and purified forms under in vitro and acute rat in vivo digestion experiments. The effect of digestion on αAI-1s was monitored by lab-on-a-chip (LOC) electrophoresis, SDS-PAGE/immunoblot, and inhibitory activity analyses by native PAGE. After both in vitro and in vivo digestion, we established that αAI-1 was not degraded even after 60 min gastric digestion and showed immune-reactive properties as well. Although the activity of the purified αAI-1 was lost, that of αAI-1 in the flour matrix (noncooked and cooked) was retained in the stomach. Presumably, in the beans, αAI-1 polypeptides became active due to the pepsin digestion of the precursor protein. The latter samples were also tested in vivo in the small intestine and their resistance and immune reactivity were observed, but αAI-1 did not show activity, as αAI-1 polypeptides were probably complexed by pancreatic amylases. From these results, we can assume that the αAI-1-rich bean protein preparation can affect the carbohydrate metabolism; thus, it could be a promising ingredient for weight loss purposes. Full article

In this study, the production of functional beverages of Zuccagnia punctata Cav. (jarilla), a native medicinal plant from Argentina, and Vaccinium corymbosum (blueberry), with lemon honey as a sweetener, is described. The beverage was formulated by using jarilla extract and blueberry juice with maltodextrin as an encapsulant material. The beverage was dried by both spray-drying and freeze-drying. Both beverages showed high water solubility with adequate features for handling, transport, and storage. The chromatic parameters indicate tones of mauve. Both the total polyphenol and flavonoid contents were retained after being spray-dried (92 and 100%, respectively). The anthocyanins were less stable under spray-dried conditions (58% retained). Both beverages showed high scavenger capacity on ABTS^•+, HO^•, and H₂O₂ (SC₅₀ between 3.56 and 36.90 µg GAE/mL) and exhibited in vitro inhibitor potential of α-glucosidase, α-amylase, and lipase activities (IC₅₀ of between 2.97 and 27.19 µg GAE/mL). The powdered beverage obtained by spray-drying presented the greatest preference in sensory tests. The beverages were neither toxic nor mutagenic in the concentration range with biological activity. During short-term storage, both beverages showed stability. The results obtained would support the use of a powdered beverage made from an Argentinean native plant and blueberries as a functional food. Full article

Investigations into the phenolic constituents of the butanolic fraction of Crataegus monogyna were optimized using LC-ESI-MS/MS analysis, identifying and quantifying at least 23 fingerprint phytochemical compounds. The major phenolic compounds were epicatechin (99.916 ± 2.208 mg/g), isoquercetrin (53.31 ± 1.172 mg/g), chlorogenic acid (47.457 ± 1.010 mg/g), quinic acid (37.819 ± 1.406 mg/g), rutin (29.98 ± 0.740 mg/g), hesperidin (5.296 ± 0.177 mg/g, detected for the first time in the C. monogyna species), astragalin (1.774 ± 0.020 mg/g), and nicotiflorin (1.482 ± 0.016 mg/g). The antioxidant properties of the lyophilized butanolic fraction were evaluated using DPPH, GOR, ABTS, CUPRAC, and reducing power assays, all of which demonstrated that there was strong activity. Additionally, the neuroprotective effect was evaluated in vitro, showing a potent inhibitory effect on acetylcholinesterase (AChE) with an IC50 of 43.65 ± 2.10 µg/mL. The antidiabetic effect was investigated through α-amylase inhibition (IC50 = 91.19 ± 0.10 µg/mL), showing high inhibitory activity. In addition, the butanolic extract exhibited significant urease inhibition with an IC50 of 26.36 ± 0.05 µg/mL. These results suggest that Algerian C. monogyna has potential as a therapeutic agent for managing diabetes complications and as a natural source of AChE inhibitors, making it a promising subject for the treatment of urease-related conditions. Its high concentrations of natural antioxidants, such as epicatechin, isoquercetrin, chlorogenic acid, quinic acid, rutin, hesperidin, and astragalin, make it suitable for integration into medicine, pharmaceuticals, cosmetics, and the food sector. Full article

The aim of this study was to compare the concentration of phenolic compounds, glucosinolates, proteins, sugars and vitamin C between kohlrabi (Brassica oleracea var. acephala gongylodes), Savoy cabbage (B. oleracea sabauda), Brussels sprouts (B. oleracea gemmifera), cauliflower (B. oleracea botrytis), radish (Raphanus sativus) and garden cress (Lepidium sativum) microgreens for their antioxidant and hypoglycemic potential. In addition, we applied an in vitro-simulated system of human digestion in order to track the bioaccessibility of the selected phenolic representatives, and the stability of the microgreens’ antioxidant and hypoglycemic potential in terms of α-amylase and α-glucosidase inhibition after each digestion phase. Using spectrophotometric and RP-HPLC methods with statistical analyses, we found that garden cress had the lowest soluble sugar content, while Savoy cabbage and Brussels sprouts had the highest glucosinolate levels (76.21 ± 4.17 mg SinE/g dm and 77.73 ± 3.33 mg SinE/g dm, respectively). Brussels sprouts were the most effective at inhibiting protein glycation (37.98 ± 2.30% inhibition). A very high positive correlation (r = 0.830) between antiglycation potential and conjugated sinapic acid was recorded. For the first time, the antidiabetic potential of microgreens after in vitro digestion was studied. Kohlrabi microgreens best inhibited α-amylase in both initial and intestinal digestion (60.51 ± 3.65% inhibition and 62.96 ± 3.39% inhibition, respectively), and also showed the strongest inhibition of α-glucosidase post-digestion (19.22 ± 0.08% inhibition). Brussels sprouts, cauliflower, and radish had less stable α-glucosidase than α-amylase inhibitors during digestion. Kohlrabi, Savoy cabbage, and garden cress retained inhibition of both enzymes after digestion. Kohlrabi antioxidant capacity remained unchanged after digestion. The greatest variability was seen in the original samples, while the intestinal phase resulted in the most convergence, indicating that digestion reduced differences between the samples. In conclusion, this study highlights the potential of various microgreens as sources of bioactive compounds with antidiabetic and antiglycation properties. Notably, kohlrabi microgreens demonstrated significant enzyme inhibition after digestion, suggesting their promise in managing carbohydrate metabolism and supporting metabolic health. Full article