Α-glucosidase Inhibitors Research Articles

Profiling of Potential Anti-Diabetic Active Compounds in White Tea: An Integrated Study of Polyphenol-Targeted Metabolomics, Network Pharmacology, and Computer Simulation.

Diabetes remains a critical global public health challenge, posing a growing threat to human health and well-being. White tea is a lightly fermented tea and one of the six traditional tea categories in China. Owing to its rich content of bioactive compounds such as catechins and alkaloids, it has demonstrated potential anti-diabetic properties. However, its precise bioactive components, mechanisms of action, and relevant molecular targets require further investigation. In this study, an integrated approach combining polyphenol-targeted metabolomics, in vitro antioxidant assays, α-glucosidase inhibition tests, network pharmacology analysis, GEO database exploration, molecular docking, and molecular dynamics simulations was employed to identify the potential anti-diabetic compounds, targets, and mechanisms of white tea. The findings revealed that white tea is particularly abundant in 10 bioactive compounds, including epigallocatechin gallate, epicatechin gallate, and catechin, all of which exhibit significant anti-diabetic potential. These compounds were found to exert their effects by interacting with core molecular targets, namely cathepsin V (CTSV) and nucleotide-binding oligomerization domain-containing protein 1 (NOD1), and engaging in pathways related to signal transduction, apoptosis, and immune responses. This study establishes a strong theoretical basis for advancing white tea research and underscores new opportunities for applying natural products in diabetes therapy.

Synthesis of newly designed hydrazones, in vitro and in silico studies, and structure-activity relationship

Herein, new N'-(substituted benzylidene)-3,5-dihydroxybenzohydrazide (1–13) series were synthesized, and their antioxidant, anticholinesterase, anti-tyrosinase, anti-urease, and antidiabetic activities were investigated together with in silico studies. The synthesized derivates were characterized using molecular spectroscopy, and the structure-activity relationships (SAR) were discussed for all tested biological assays. According to activity results, compound 3 exhibited excellent antioxidant activity in all tests, while compound 1 demonstrated the best acetylcholinesterase (AChE) inhibitory and butyrylcholinesterase (BChE) inhibitory activities. On the other hand, compound 11 showed excellent tyrosinase inhibitory (IC50:3.02±0.10 mM) and urease inhibitory (IC50:9.21±0.27 µM) activity. Moreover, among the synthesized compounds, compound 6 was detected as the best antidiabetic compound by inhibiting α-amylase (IC50:30.68±0.94 µM) and α-glycosidase (IC50:41.35±0.03 µM) enzymes, which were related with the antidiabetic activity. Molecular docking analysis confirmed AChE, BChE, tyrosinase, urease, α-amylase, and α-glucosidase inhibitory activities. In line with the findings obtained from in vitro bioactivity results and molecular docking analysis, hydrazone compounds are a suitable class of organic compounds for developing acetylcholinesterase, butyrylcholinesterase, urease, α-amylase, and α-glucosidase inhibitors.

Chemical Composition and Biological Activity of Hypericum Species-H. hirsutum, H. barbatum, H. rochelii.

St. John's wort (Hypericum perforatum, Hypericaceae) is the most well-known species in the genus Hypericum, which comprises several hundred species. This study investigates the biological and phytochemical potential of the under-researched Hypericum species, H. hirsutum, H. barbatum, and H. rochelii. A high level of similarity between the chemical profiles of H. hirsutum and H. barbatum and the official source of the herbal drug (H. perforatum) was shown, but a higher content of quercetin and rutin was also found in all three evaluated species (116-230 µg/g dry herb). The highest amount of phenolics (195 mg GAE/g) was recorded in H. hirsutum extract, while the highest amount of flavonoids (47 mg QE/g) was recorded in H. barbatum extract. The evaluated species were excellent scavengers of DPPH, OH, and NO radicals, as well as strong ferric ion reducers in the FRAP test. Prominent monoamine oxidase A and α-glucosidase inhibition was observed, compared to modest inhibition of monoamine oxidase B, α-amylase, and acetylcholinesterase. High activity against Gram-positive MRSA S. aureus was demonstrated for the tested species, with MIC/MBC values recorded at 12.5 µg/mL. Antifungal activity against Candida strains was not observed. The obtained results emphasize the need for further investigation of species of the genus Hypericum to discover potentially new sources of biologically active compounds.

Exploring the 3,5-Dibromo-4,6-dimethoxychalcones and Their Flavone Derivatives as Dual α-Glucosidase and α-Amylase Inhibitors with Antioxidant and Anticancer Potential.

The rising levels of type 2 diabetes mellitus (T2DM) and the poor medical effects of the commercially available antidiabetic drugs necessitate the development of potent analogs to treat this multifactorial metabolic disorder. It has been demonstrated that targeting two or more biochemical targets associated with the onset and progression of diabetes along with oxidative stress and/or cancer could be a significant strategy for treating complications related to this metabolic disorder. The 3,5-dibromo-4,6-dimethoxychalcones (2a-f) and the corresponding flavone derivatives (3a-f) were synthesized and characterized using spectroscopic (NMR, HR-MS and FT-IR) techniques. The inhibitory effect of both series of compounds against α-glucosidase and α-amylase was evaluated in vitro through enzymatic assays. Selected compounds were also evaluated for potential to activate or inhibit superoxide dismutase. Compound 3c was selected as a representative model for the flavone series and evaluated spectrophotometrically for potential to coordinate Cu(II) and/or Zn(II) ions implicated in the metal-catalyzed free radical generation. A plausible mechanism for metal-chelation of the test compounds is presented. Furthermore, the most active compounds from each series against the test carbohydrate-hydrolyzing enzymes were selected and evaluated for their antigrowth effect on the human breast (MCF-7) and lung (A549) cancer cell lines and for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The parent chalcone 2a and flavone derivatives 3a, 3c and 3e exhibited relatively high inhibitory activity against the MCF-7 cells with IC50 values of 4.12 ± 0.55, 8.50 ± 0.82, 5.10 ± 0.61 and 6.96 ± 0.66 μM, respectively. The chalcones 2a and 2c exhibited significant cytotoxicity against the A549 cells with IC50 values of 7.40 ± 0.67 and 9.68 ± 0.80 μM, respectively. Only flavone 3c exhibited relatively strong and comparable cytotoxicity against the MCF-7 and A549 cell lines with IC50 values of 6.96 ± 0.66 and 6.42 ± 0.79 μM, respectively. Both series of compounds exhibited strong activity against the MCF-7 and A549 cell lines compared to the analogous quercetin (IC50 = 35.40 ± 1.78 and 35.38 ± 1.78 μM, respectively) though moderate compared to nintedanib (IC50 = 0.53 ± 0.11 and 0.74 ± 0.15 μM, respectively). The test compounds generally exhibited reduced cytotoxicity against the Vero cells compared to this anticancer drug. Molecular docking revealed strong alignment of the test compounds with the enzyme backbone to engage in hydrogen bonding interaction/s and hydrophobic contacts with the residues in the active sites of α-glucosidase and α-amylase. The test compounds possess favorable drug-likeness properties, supporting their potential as therapeutic candidates against T2DM.

Hypoglycemic Properties of Leccinum scabrum Extracts-An In Vitro Study on α-Glucosidase and α-Amylase Inhibition and Metabolic Profile Determination.

Type-2 diabetes affects an increasing percentage of the world's population and its control through dietary management, involving the consumption of health-promoting foods or their derived supplements, is a common strategy. Several mushroom species have been demonstrated to be endowed with antidiabetic properties, resulting from their ability in improving insulin sensitivity and production, or inhibiting the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase. This study aimed to investigate for the first time the hypoglycemic properties of the edible mushroom Leccinum scabrum (Bull.) Gray. Mushroom extracts were prepared through the microwave-assisted extraction (MAE) technique using green solvents with different polarity degrees. The inhibition activity of all the obtained extracts on both α-glucosidase and α-amylase was evaluated and the highest activity was observed for the EtOAc extract which showed an IC50 value about 60-fold lower than the reference compound 1-deoxynojirimycin (DNJ) on α-glucosidase (0.42 ± 0.02 and 25.4 ± 0.6 µg/mL, respectively). As expected on the basis of the literature data concerning both α-glucosidase and α-amylase inhibition, a milder inhibition activity on pancreatic α-amylase was observed. Preliminary in vivo tests on Drosophila melanogaster carried out on the most active obtained extract (EtOAc) confirmed the in vitro observed hypoglycemic activity. Finally, the EtOAc extract metabolic profile was determined through GC-MS and HRMS analyses.

Epicatechin Isolated from Litchi chinensis Sonn. (Litchi) Fruit Peel Ethyl Acetate Extract Modulated Glucose Uptake in Chang Cells and Suppressed ROS Production in RAW 264.7 Macrophages.

Bioactive flavonoid epicatechin has been reported in the peel of litchi fruit but isolated from its hydroalcoholic extracts. This study isolated epicatechin with cellular glucose uptake modulatory and ROS production inhibitory properties from the ethyl acetate (EtOAc) extract using a bioassay-guided approach. The fruit peel was defatted with hexane and sequentially extracted using dichloromethane (DCM), EtOAc, methanol (MeOH) and water. In vitro phytochemical models, namely antioxidant (Fe3+ reducing, radical scavenging and anti-linoleic acid peroxidative) and glycaemic control (α-glucosidase and α-amylase inhibitory and glucose uptake modulatory), were employed for the bioassay-guided isolation, while the isolated compound was characterised using NMR and mass spectrometry and assessed for dose-dependent inhibition of α-glucosidase and lipopolysaccharide (LPS)-induced cellular ROS production, as well as modulation of cellular glucose uptake. Relative to the other extracts, the EtOAc extract had appreciable phenol and flavonoid contents, which perhaps influenced its potent anti-lipid peroxidative (65.0%) and α-glucosidase inhibitory (52.4%) effects. The α-glucosidase inhibitory potency of the fractions (1-8) from the EtOAc extracts correlated with their flavonoid contents, with fraction 5 outperforming other fractions. The fraction comprised a pool of fractions obtained from the DCM:MeOH:water (7:3:0.281 v/v/v) solvent system. LC-MS revealed the predominant presence of epicatechin in fraction 5, which was later isolated from one of the sub-fractions (sub-fraction 4) of fraction 5. This sub-fraction had stronger anti-lipid peroxidative (65.5%), α-glucosidase inhibitory (65.8%) and glucose uptake modulatory (38.2%) effects than the other sub-fractions from fraction 5, which could have been influenced by the isolated epicatechin. Moreover, the isolated epicatechin inhibited α-glucosidase (IC50 = 35.3 µM), modulated cellular glucose uptake (EC50 = 78.5 µM) and inhibited LPS-induced ROS production in RAW 264.7 macrophages in a dose-dependent fashion [IC50 = 18.9 µM; statistically comparable (p > 0.05) to ascorbic acid, IC50 = 9.57 µM]. Epicatechin from litchi peel EtOAc extract could potentiate glucose uptake modulatory, α-glucosidase inhibitory and ROS suppressive capacities, which could be influential in the use of litchi fruit peel for managing diabetes and associated oxidative damage.

Potent α-glucosidase inhibitors with benzimidazole-propionitrile hybridization; synthesis, bioassay and docking study.

Background: Diabetes is characterized by a lack of insulin and insensitivity to insulin. In 2013, the global diabetes population was 382million, with 90% of them having type 2 diabetes (non-insulin-dependent). It is predicted that this number will increase to 592million by 2035.Aim: Here, we aimed to synthesize a series of benzimidazole-based derivatives B1-B32 with α-glucosidase inhibition potential as antidiabetic agents.Methods: Compounds B1-B32 were prepared in three three-step reactions, and the structures were elucidated using spectroscopic methods, namely 1H NMR, 13C NMR, MS and IR. Enzyme inhibition and kinetic study were done using commercial assay kits, and molecular docking study using autodock4.Results: Bioassay data showed that twenty-four out of the thirty-two tested compounds exhibited IC50 values ranging from 44 to 745μM, surpassing the standard molecule, acarbose (IC50: 750μM). it was determined that the best compound, B10, functions as a competitive inhibitor. Additionally, a molecular docking study provided insights into the interactions between the four most promising compounds (B5, B6, B10 and B28) and the active site residues within the enzyme.Conclusion: The tested compounds are interesting α-glucosidase inhibitors, which indicates the benefit of more bioassay studies, especially in vivo studies.

Characterization, biological activity and photodegradation efficacy of synthesized tryptophan capped silver nanoparticles

Tryptophan capped Silver nanoparticles (AgNPs) were synthesized through a sonochemical method, utilizing tryptophan as a biocompatible and non-toxic capping agent. Based on UV–visible spectra, the optical band gap of the nanoparticles was found to be roughly 3.01 eV. The TEM and XRD measurements of the particle sizes showed a range of 10–22 nm. Under sun irradiation, these nanoparticles showed notable photocatalytic activity, destroying Methylene Blue (MB) dye by more than 79.4 %. With a pseudo-first-order apparent rate constant of 1.5×10−2min-1, the degradation kinetics were observed. The photocatalysis of MB dye was investigated using liquid chromatography in conjunction with electrospray ionization time-of-flight mass spectrometry (LC-ESI-TOF-MS) to determine the products generated and to clarify the degradation processes. Additionally, the antibacterial, anticancer potential showed thate the nanoparticles exhibited good antibacterial and notable anticancer properties. Furthermore, the antidiabetic activity was investigated through α-glucosidase inhibition, demonstrating a significant inhibition rate of 53.98 %. Antioxidant capabilities were also tested using ABTS and DPPH assays, revealing antioxidant activities of 73.9 % and 52.04 %, respectively. Overall, the synthesized tryptophan-capped AgNPs show promising applications in environmental remediation, as well as potential therapeutic uses.

Effect of Complexation with Different Molecular Weights of Oat β-Glucan and Sea Buckthorn Flavonoid on the Digestion of Rice Flour.

The complex of oat β-glucan (OBG) and flavonoids hampered the digestion of starch-based food and retarded the blood glucose response; however, its effect on gastric emptying and its relative mechanism have not been thoroughly investigated. By using Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), antioxidant ability, and enzymic inhibitory tests for the characterization and in vitro semi-dynamic digestion of complexes of OBG (high and low molecular weights) and sea buckthorn flavonoids, we found that the higher molecular weight complex (FU) exhibited stronger ABTS and DPPH radical scavenging abilities and higher α-glucosidase and α-amylase inhibition rates. Mice fed with rice flour with FU addition exhibited the slowest gastric emptying and intestinal propulsion rates and blood glucose rise and had the lowest activity of digestive enzymes and levels of insulin, ghrelin, motilin (MTL), and relevant gene (ghrelin and GHSR mRNA) expression than those in the control and low-molecular-weight groups. This study provided scientific data for the development of foods with delayed gastric rate and hypoglycemic index for specific populations.

Stevia By-product Fraction has Antioxidant Capacity and has been Evaluated for its Antihyperglycemic and Antilipid Potential

Introduction/Objective: The ethanolic pretreatment of stevia leaves is considered ecologically favorable and increases its yield, purity level, and sensory profile of sweeteners. We investigated the by-product generated so that we can provide a viable and applicable destination to effectively contribute to the production and industrial chain of stevia sweeteners. Recently, an antioxidant and antidiabetic fraction was obtained through stevia methanolic extraction. However, this process is costly, has a low yield, and is non-green. In this study, we got an antioxidant fraction of stevia from its pretreatment by-product, the ethanolic extract, characterized its bioactive compounds – mainly phenolic acids and flavonoids – and evaluated its antidiabetic and antilipid capacity. Methods: The ethanolic extract was fractionated, then the ethyl acetate fraction was microencapsulated. Physicochemical, Mass Spectrometry (UHPLC/MS-MS), scanning electron microscopy, microencapsulation efficiency, and antioxidant capacity analyses were carried out. The antioxidant capacity was evaluated. Antihyperglycemic capacity was assessed by inhibition of α-glucosidase and α-amylase. For antilipid potential, inhibition of pancreatic lipase was measured. Results: Antioxidant potential was observed mainly in the fraction. Microencapsulation improved the stability of the fraction. Mass spectrometry allowed comparison with phenolic and flavonoid compounds from the methanolic and ethanolic fractions of the by-product. Many compounds were coincident, which may explain the similar antioxidant capacity found. The samples showed more than 90% inhibition of alpha-glucosidase, which may indicate potential antidiabetic activity. All samples showed inhibition of the pancreatic lipase enzyme higher than 80%, reaching 91.05% for the free fraction. Conclusion: This study represented the recovery of a by-product and showed that this antioxidant fraction deserves further investigation for its bioactive potential, especially antioxidant, antidiabetic, and anti-lipid.

Exploring synergistic inhibitory mechanisms of flavonoid mixtures on α-glucosidase by experimental analysis and molecular dynamics simulation

The study was the first to evaluate the synergistic interaction of luteolin + quercetin, luteolin + 3-O-methylquercetin, and quercetin + 3-O-methylquercetin mixtures on α-glucosidase and the binding mechanisms were explored using both experimental and theoretical approaches. The results showed that three flavonoid mixtures exhibited a mixed type of inhibition and demonstrated the most potent synergistic effects on α-glucosidase inhibition at 6:4 ratio, with interaction index (γ) of 0.85, 0.78 and 0.73, respectively. The three mixtures had a great influence on α-glucosidase secondary structures. Molecular simulation further demonstrated that three flavonoid mixtures formed hydrophobic interactions and hydrogen bonds with amino acid residues at different sites of α-glucosidase. Collectively, luteolin + quercetin, luteolin + 3-O-methylquercetin and quercetin + 3-O-methylquercetin were found to inhibit α-glucosidase in a synergistic manner and can be potentially used for the development of hypoglycemic food products.

A Comprehensive Review of Moroccan Medicinal Plants for Diabetes Management.

Moroccan flora, renowned for its diverse medicinal plant species, has long been used in traditional medicine to manage diabetes. This review synthesizes ethnobotanical surveys conducted during the last two decades. Among these plants, 10 prominent Moroccan medicinal plants are evaluated for their phytochemical composition and antidiabetic properties through both in vitro and in vivo studies. The review encompasses a comprehensive analysis of the bioactive compounds identified in these plants, including flavonoids, phenolic acids, terpenoids, and alkaloids. Phytochemical investigations revealed a broad spectrum of secondary metabolites contributing to their therapeutic efficacy. In vitro assays demonstrated the significant inhibition of key enzymes α-amylase and α-glucosidase, while in vivo studies highlighted their potential in reducing blood glucose levels and enhancing insulin secretion. Among the ten plants, notable examples include Trigonella foenum-graecum, Nigella Sativa, and Artemisia herba-alba, each showcasing distinct mechanisms of action, such as enzymatic inhibition and the modulation of glucose metabolism pathways. This review underscores the necessity for further chemical, pharmacological, and clinical research to validate the antidiabetic efficacy of these plants and their active compounds, with a view toward their potential integration into therapeutic practices.

α-GLUCOSIDASE AND TYROSINASE INHIBITORY GUIDED ISOLATION, IDENTIFICATION OF MAJOR COMPOUND AND IN SILICO STUDY FROM EDIBLE MUSHROOM COPRINUS COMATUS

Coprinus comatus is an edible and medicinal mushroom. The crude hexane, EtOAc and methanol extracts were extracted successively from C. Comatus. All the crude extracts were evaluated for anti-a-glucosidase and tyrosinase. The results showed that %inhibition valued for the crude hexane, EtOAc and methanol extracts of anti-a-glucosidase were 98.58 ± 0.09, 98.90 ± 0.21, and 6.68 ± 0.79, respectively. The anti-tyrosinase for the crude hexane, EtOAc and methanol extracts were 97.31 ± 2.77, 97.31 ± 3.34 and 64.94 ± 3.34, respectively. Notably, the bioassay-guided showed that the crude hexane and EtOAc were the highest for anti-a-glucosidase and tyrosinase activities, which led to the interest in purifying the major compound. The isolation and purification were successively done using chromatographic techniques. The pure compounds were determined by spectroscopic analysis (UV, FTIR, and NMR) and comparison with previously reported. The isolation led to three compounds (1-3), ergosterol (1), indole-3-carbaldehyde (2), and 4-hydroxybenzoic acid (3). The molecular docking of compounds 1-3, reported as α-glucosidase and tyrosinase inhibitors, was done by the AutoDockTools 1.5.6 (ADT) software. The results revealed that ergosterol (1) provides the highest binding free energy (-9.91 kcal/mol) to the active site of a-glucosidase, indicating that it is quite specific to this enzyme. Moreover, ergosterol (1) has strong binding energy (-9.64 kcal/mol) to tyrosinase but not significant tyrosinase specificity. This evidence supports that C. Comatus would be applicable for a functional food for controlling glucose blood levels.

Investigating the efficacy of naphthalene-thiazole hybrid hydrazones as α-glucosidase inhibitors

In this study, a series of hydrazone derivatives containing naphthalene and thiazole hybrids were synthesized through the condensation of (E)-4-methyl-2-(2-(naphthalen-1-ylmethylene)hydrazineyl) thiazole-5-carbohydrazide with various carbonyl compounds, including aldehydes and ketones, whether carbocyclic aromatic or heterocyclic, using a grinding method with drops of acetic acid. The elucidation of the structures of the synthesized hydrazone derivatives was achieved through the analysis of NMR, IR, and mass spectrometry data. All the newly prepared compounds were assessed for their in vitro α-glucosidase inhibition profiles and the results revealed a diverse range of inhibitory potentials, ranging from 9.3 ± 1.0 to 70.5 ± 1.8 μM, in contrast to the reference acarbose (with an IC50 value of 45.2 ± 1.3 μM). In an attempt to explain the observed inhibitions of synthesized naphthalene containing thiazole compounds, molecular docking was performed to determine the binding modes between the synthesized compounds from one side and the active residues of α-glucosidase from the other side. Compounds 4d, 4e, 4c, and 8 demonstrated the strongest binding affinities, with binding energies of -10.5, -9.8, -9.6, and -9.5 kcal/mol, respectively.

In vitro Anti-Diabetic and Antioxidant Potential of the Siddha formulation Mega Sanjeevi Chooranam

Background: The increasing prevalence of type 2 diabetes mellitus (T2DM) presents a significant public health challenge due to its long-term complications and its role as a primary risk factor for cardiovascular diseases, which have both economic and social implications. Plant-derived antidiabetic drugs are being extensively studied due to their safety and efficacy. The main objective of the present study is to evaluate the anti-diabetic and anti-oxidant potential of the formulation Mega Sanjeevi Chooranam (MSC) through in-vitro investigation. Materials and Methods: The in vitro investigation of traditional siddha formulation MSC were performed to ascertain its inhibitory potential against α-amylase and α-glucosidase enzymes along with antioxidant analysis. Results: The MSC displayed the highest activity against α-amylase enzyme, with a percentage inhibition of 73.44 ± 6.87% (IC50, 299.4 ± 27.27 μg/ml), followed by a moderate level of α-glucosidase inhibition at 48.89 ± 13.38% (IC50, 402.2 ± 86 μg/ml). Furthermore, the MSC exhibited the strongest antioxidant activity in quenching ABTS● radicals (IC50, 110.1 ± 18.6 μg/ml), followed by DPPH● (IC50, 144.4 ± 36.8 μg/ml), H2O2● (IC50, 172.7 ± 39.3 μg/ml), and NO● radicals (IC50, 238.4 ± 58.56 μg/ml). Conclusion: In conclusion the formulation MSC demonstrated the significant antioxidant activity and effectively inhibited α-amylase and α-glucosidase enzyme activities. Further study is needed to isolate bioactive phytoconstituents and determine the molecular mechanism behind their antidiabetic effect.

In vivo anti-diabetic and anti-lipidemic evaluations of an excellent synthetic α-glucosidase inhibitor with dihydropyrano[3,2-c]quinoline skeleton

In vivo anti-diabetic and anti-lipidemic evaluations of an excellent synthetic α-glucosidase inhibitor with dihydropyrano[3,2-c]quinoline skeleton

Design, synthesis and enzymatic inhibition evaluation of novel 4-hydroxy Pd–C-Ⅲ derivatives as α-glucosidase and PTP1B dual-target inhibitors

A library of 4-Hydroxy Pd–C-Ⅲ derivatives (5a-5p and 8a-8h) as α-glucosidase inhibitors was prepared and the activity of these compounds against α-glucosidase was evaluated. The outcomes displayed that most of the derivatives had moderate to potent α-glucosidase inhibition with IC50 values ranging from 66.3 ± 2.4 to 299.7 ± 6.0 μM. Amongst these compounds, 8a had the strongest α-glucosidase inhibition than others with an IC50 value of 66.3 ± 2.4 μM. Therefore, 8a was chosen to detect the inhibitory activities on PTP1B and α-amylase, the results revealed that 8a had the potential to be PTP1B (IC50 = 47.0 ± 0.5 μM) and α-amylase (IC50 = 30.62 ± 2.13 μM) inhibitor. Additionally, the enzyme kinetic study displayed that 8a was a mixed-type inhibitor. Moreover, the results of the spectroscopy experiments proved that 8a could quench the fluorescence intensity of α-glucosidase in a dose-dependent manner, destroy the secondary structure of α-glucosidase and change the conformation of the enzyme. Significantly, the investigation of cellular thermal shift assay exhibited that 8a could target the PTP1B protein, and the in vitro cytotoxicity discovered compound 8a had no significant toxicity to normal HEK-293 cells. Additionally, the results of molecular docking found that 8a could both bind the active sites of the α-glucosidase and PTP1B. Importantly, the in vivo sucrose-loading test displayed 8a had potential to reduce the postprandial blood glucose. All results proved that compound 8a had great potential as a dual-target inhibitor in treating Type 2 diabetes mellitus.

Extraction, Structural Characterization, and Physicochemical and Biological Properties of Water-Soluble Polysaccharides from Adlay Bran.

Adlay bran, often discarded or used as animal feed, holds untapped potential. This study explores the beneficial properties of water-soluble polysaccharides (ABPs), extracted using a hot water method, with the aim of transforming what is commonly regarded as waste into a valuable resource. The response surface methodology (RSM) was employed to fine-tune the extraction parameters, establishing conditions at 80.0 °C, 2.5 h, and a water-to-material ratio of 31.6 mL/g. Structural studies showed that ABPs consist of different monosaccharides, including rhamnose, arabinose, glucosamine, glucose, galactose, xylose, mannose, and glucuronic acid, with respective molar ratios of 2.12%, 2.40%, 0.52%, 77.12%, 7.94%, 3.51%, 2.55%, and 3.82%. The primary component of these polysaccharides has a molecular weight averaging 12.88 kDa. The polysaccharides feature eight distinct linkage types: →3,4)-Rhap-(1→ at 5.52%, →4)-Glcp-(1→ at 25.64%, Glcp-(1→ at 9.70%, →3,4)-Glcp-(1→ at 19.11%, →4)-Xylp-(1→ at 7.05%, →3)-Glcp-(1→ at 13.23%, →3,4)-Galp-(1→ at 9.26%), and →4,6)-Gclp-(1→ at 12.49%. The semi-crystalline properties of ABPs and their shear-thinning characteristics were validated by X-ray diffraction and rheology tests. In vitro assays highlighted the strong antioxidant activities of ABPs, as evidenced by DPPH and ABTS hydroxyl radical scavenging tests, along with significant metal chelating and reducing powers. Additionally, ABPs showed significant inhibition of α-glucosidase and α-amylase, making them attractive as versatile additives or as agents with antioxidant and blood-sugar-lowering properties in both the food and pharmaceutical sectors. These findings support the utilization of adlay bran for higher-value applications, harnessing its bioactive components for health-related benefits.

Antioxidant, antibacterial, and α-glucosidase inhibition potential of three Allium species (Amaryllidaceae) from Iran

Introduction: Wild species of the genus Allium have high potential for use as medicine due to their essential secondary metabolites with antioxidant activity. This study explored the antioxidant, antibacterial, and α-glucosidase inhibition activities of three Allium species: Allium tripedale, Allium hooshidaryae, and Allium stipitatum. Methods: The antioxidant potentials of the plant methanol extracts were evaluated using the ferric reducing antioxidant power (FRAP) and the 2,2-diphenyl-1picrylhydrazil (DPPH) radical scavenging test. Total phenolic content (TPC), total flavonoid content (TFC) and α-glucosidase inhibition were also evaluated. Antibacterial assessments were done employing disk diffusion and microdilution methods to determine inhibition zone and minimum inhibitory concentration (MIC), respectively against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. Results: Allium hooshidaryae displayed high TPC (70.24 ± 0.0039 mg gallic acid equivalent/g extract), while A. tripedale had the highest TFC (87 ± 0.013 mg Quercetin equivalent/g extract). A. hooshidaryae showed superior antioxidant capacity (DPPH IC50: 724.4 ± 0.31 µg/mL; FRAP: 36.87 mg ascorbic acid equivalent/g extract) and stronger α-glucosidase inhibition (IC50 = 2.59 mg/mL vs. 4.33 mg/mL for A. tripedale and 6.41 mg/mL for A. stipitatum). Qualitative tests confirmed phenolic, flavonoid, and glycoside compounds in all three species. A. stipitatum uniquely contained saponin and tannin. A. hooshidaryae and A. stipitatum inhibited the bacterial strains effectively, especially at the higher concentration (400 µg/mL). A. stipitatum showed inhibition against all strains, particularly against S. aureus (MIC: 12.5 µg/mL). Conclusion: This study highlights the antidiabetic and antibacterial potential of three Allium species, emphasizing their values as rich sources of bioactive compounds.

Employing Machine Learning Models to Predict Potential α-Glucosidase Inhibitory Plant Secondary Metabolites Targeting Type-2 Diabetes and Their In Vitro Validation.

The need for new antidiabetic drugs is evident, considering the ongoing global burden of type-2 diabetes mellitus despite notable progress in drug discovery from laboratory research to clinical application. This study aimed to build machine learning (ML) models to predict potential α-glucosidase inhibitors based on the data set comprising over 537 reported plant secondary metabolite (PSM) α-glucosidase inhibitors. We assessed 35 ML models by using seven different fingerprints. The Random forest with the RDKit fingerprint was the best-performing model, with an accuracy (ACC) of 83.74% and an area under the ROC curve (AUC) of 0.803. The resulting robust ML model encompasses all reported α-glucosidase inhibitory PSMs. The model was employed to predict potential α-glucosidase inhibitors from an in-house 5810 PSM database. The model identified 965 PSMs with a prediction activity ≥0.90 for α-glucosidase inhibition. Twenty-four predicted PSMs were subjected to in vitro assay, and 13 were found to inhibit α-glucosidase with IC50 ranging from 0.63 to 7 mg/mL. Among them, seven compounds recorded IC50 values less than the standard drug acarbose and were investigated further to have optimal drug-likeness and medicinal chemistry characteristics. The ML model and in vitro experiments have identified nervonic acid as a promising α-glucosidase inhibitor. This compound should be further investigated for its potential integration into the diabetes treatment system.