Screening of Potential α-Glucosidase Inhibitors from the Roots and Rhizomes of Panax Ginseng by Affinity Ultrafiltration Screening Coupled with UPLC-ESI-Orbitrap-MS Method.

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening.

Antioxidant and hypoglycemic potential of phytogenic cerium oxide nanoparticles.

Plants provide humans with more than just food and shelter; they are also a major source of medications. The purpose of this research was to investigate the antioxidant and hypoglycemic potential of green synthesized CeONPs using Mentha royleana leaves extract. The morphological and physicochemical features of CeONPs were evaluated by UV-Visible spectrophotometry, Scanning Electron Microscopy, Energy Dispersive X-rays and Fourier-transform infrared spectrometry, Dynamic light scattering, Atomic Force Microscopy, Zeta Potential. The average size range of synthesized CeONPs diameter between 46 and 56 nm, crystalline in shape, with Polydispersity index value of 0.2 and subatomic particles mean diameter was 4.5-9.1 nm. The antioxidant capability of CeONPs was assessed using DPPH, ABTS+, hydrogen peroxide, hydroxyl radical scavenging, and reducing power tests. The hypoglycemic potential of CeONPs was investigated using alpha-amylase, alpha-glucosidase, glucose absorption by yeast cells, and antisucrase. The effective concentrations were 500 and 1000 µg/ml found good in suppressing radical species. To explore the hypoglycemic potential of CeONPs, alpha-amylase, alpha-glucosidase, glucose absorption by yeast cell, and antisucrase assays were performed. Glucose absorb by yeast cells assay was tested for three distinct glucose concentrations: 5 mmol/L, 10 mmol/L, and 25 mmol/L. Green synthesize CeONPs showed a dose-dependent response, higher concentrations of CeONPs imposed a stronger inhibitory impact on the catalytic site of enzymes. This study suggest that CeONPs could possibly binds to the charge carrying species and act as competitive inhibitor which slow down the enzyme substrate reaction and prevents enzymatic degradation. The study's findings were outstanding, which bodes well for future medicinal applications of CeONPs.

Assessment of the antidiabetic potential of extract and novel phytoniosomes formulation of Tradescantia pallida leaves in the alloxan-induced diabetic mouse model.

Diabetes inflicts health and economic burdens on communities and the present antidiabetic therapies have several drawbacks. Tradescantia pallida leaves have been used as a food colorant and food preservative; however, to our knowledge antidiabetic potential of the leaves of T. pallida has not been explored yet. The current study aimed to investigate the antidiabetic potential of T. pallida leaves extract and its comparison with the novel nisosome formulation of the extract. The leaves extract and phytoniosomes of T. pallida in doses of 15, 25 and 50 mg/kg were used to assess the oral glucose loaded, and alloxan-induced diabetic mice models. The biological parameters evaluated were; change in body weight, blood biochemistry, relative organ to body weight ratio and histopathology of the liver, pancreas and kidney. Results revealed that the extract 50 mg/kg and phytoniosomes 25 and 50 mg/kg remarkably reduced the blood glucose level in all hyperglycemic mice by possibly inhibiting α-amylase and α-glucosidase production. Body weight and blood biochemical parameters were considerably improved in phytoniosomes 50 mg/kg treated group. The relative body weight was similar to those of healthy mice in extract 50 mg/kg, phytoniosomes 25 mg/kg, and phytoniosomes 50 mg/kg treated groups. Histopathology showed the regeneration of cells in the CHN50 treated group. Hyphenated chromatographic analysis revealed potent metabolites, which confirmed the antidiabetic potential of the extract by inhibiting α-amylase and α-glucosidase using in silico analysis. The present data suggested that phytoniosomes have shown better antidiabetic potential than crude extract of these leaves.

Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease.

The survival of infantile-onset Pompe disease (IOPD) patients has improved dramatically since the introduction of enzyme replacement therapy (ERT) with a1glucosidase alfa. However, long-term IOPD survivors on ERT demonstrate motor deficits indicating that current therapy cannot completely prevent disease progression in skeletal muscle. We hypothesized that in IOPD, skeletal muscle endomysial stroma and capillaries would show consistent changes that could impede the movement of infused ERT from blood to muscle fibers. We retrospectively examined 9 skeletal muscle biopsies from 6 treated IOPD patients using light and electron microscopy. We found consistent ultrastructural endomysial stromal and capillary changes. The endomysial interstitium was expanded by lysosomal material, glycosomes/glycogen, cellular debris, and organelles, some exocytosed by viable muscle fibers and some released on fiber lysis. Endomysial scavenger cells phagocytosed this material. Mature fibrillary collagen was seen in the endomysium, and both muscle fibers and endomysial capillaries showed basal laminar reduplication and/or expansion. Capillary endothelial cells showed hypertrophy and degeneration, with narrowing of the vascular lumen. Ultrastructurally defined stromal and vascular changes likely constitute obstacles to movement of infused ERT from capillary lumen to muscle fiber sarcolemma, contributing to the incomplete efficacy of infused ERT in skeletal muscle. Our observations can inform approaches to overcoming these barriers to therapy.

Synthesis and structure-activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors.

In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC50 value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC50 value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors.

Phytochemical profile and antioxidant capacity, α-amylase and α-glucosidase inhibitory activities of Oxalis pes-caprae extracts in alloxan-induced diabetic mice.

Diabetes and its complications are closely correlated with chronic hyperglycemia, causing severe oxidative stress and leading to glycation reaction with formation of advanced glycation end products. However, medicinal plants are still a source of inspiration for the discovery of new treatments of several diseases, including diabetes. The present study was aimed to evaluate the antioxidant and antidiabetic properties of Oxalis pes-caprae flowers extract in alloxan-induced diabetic mice. The phytochemical and antioxidant activities of both aqueous and methanolic extracts were assessed by in-vitro testing such as free radical scavenging assays (DPPH and ABTS+), ferrous ions (Fe2+) chelating activity and reducing power assay. Additionally, the detection of Amadori products and advanced glycation end products was used to determine the antiglycation potential. α-glucosidase and α-amylase inhibitory assessment was employed to determine the antidiabetic effect, while alloxan-induced diabetic mice were used to measure the in-vivo activities of antioxidants and carbohydrates enzymes. The effect of the methanolic extract on body weight and blood glucose level of extract-treated diabetic mice were also investigated. Among the tested extract, the methanolic extract was the richest in phenolic compounds which is directly related with their remarkable antioxidant, enzyme inhibitory and antiglycation activity. The oral administration of the two doses of Oxalis pes-caprae flowers (150 mg/kg and 250 mg/kg) daily for 3 weeks resulted in hypoglycemic effect compared to the reference drug, glibenclamide (10 mg/kg). Furthermore, the extract was shown to significantly increase the activities of antioxidants and glycolysis enzymes in the liver, kidney and spleen of diabetic mice, compared to diabetic control group. Therefore, Oxalis pes-caprae extract effectively exhibited hypoglycemic and antidiabetic effects as indicated by in-vitro and in-vivo studies, confirming the protective effects on hyperglycemia and oxidative damage.

Transcriptomic characterization of clinical skeletal muscle biopsy from late-onset Pompe patients.

Pompe disease is a rare lysosomal storage disorder arising from recessive mutations in the acid α-glucosidase gene and resulting in the accumulation of glycogen, particularly in the cardiac and skeletal muscle. The current standard of care is administration of enzyme replacement therapy in the form of alglucosidase alfa or the recently approved avalglucosidase alfa. In order to better understand the underlying cellular processes that are disrupted in Pompe disease, we conducted gene expression analysis on skeletal muscle biopsies obtained from late-onset Pompe disease patients (LOPD) prior to treatment and following six months of enzyme replacement with avalglucosidase alfa. The LOPD patients had a distinct transcriptomic signature as compared to control patient samples, largely characterized by perturbations in pathways involved in lysosomal function and energy metabolism. Although patients were highly heterogeneous, they collectively exhibited a strong trend towards attenuation of the dysregulated genes following just six months of treatment. Notably, the enzyme replacement therapy had a strong stabilizing effect on gene expression, with minimal worsening in genes that were initially dysregulated. Many of the cellular process that were altered in LOPD patients were also affected in the more clinically severe infantile-onset (IOPD) patients. Additionally, both LOPD and IOPD patients demonstrated enrichment across several inflammatory pathways, despite a lack of overt immune cell infiltration. This study provides further insight into Pompe disease biology and demonstrates the positive effects of avalglucosidase alfa treatment.

Synthesis and biological evaluation of 2,5-disubstituted furan derivatives containing 1,3-thiazole moiety as potential α-glucosidase inhibitors.

α-Glucosidase, which is involved in the hydrolysis of carbohydrates to glucose and directly mediates blood glucose elevation, is a crucial therapeutic target for type 2 diabetes. In this work, 2,5-disubstituted furan derivatives containing 1,3-thiazole-2-amino or 1,3-thiazole-2-thiol moiety (III-01 âˆ¼ III-30) were synthesized and screened for their inhibitory activity against α-glucosidase. α-Glucosidase inhibition assay demonstrated that all compounds had IC50 in the range of 0.645-94.033 µM and more potent than standard inhibitor acarbose (IC50 = 452.243 ± 54.142 µM). The most promising inhibitors of the two series were compound III-10 (IC50 = 4.120 ± 0.764 µM) and III-24 (IC50 = 0.645 ± 0.052 µM), respectively. Kinetic study and molecular docking simulation revealed that compound III-10 (Ki = 2.04 ± 0.72 µM) is a competitive inhibitor and III-24 (Ki = 0.44 ± 0.53 µM) is a noncompetitive inhibitor against α-glucosidase. Significantly, these two compounds showed nontoxicity towards HEK293, RAW264.7 and HepG2 cells, suggesting that compounds may be considered as a class of potential candidates for further developing novel antidiabetic drugs.

Design and Synthesis of Sulfonium Derivatives: A Novel Class of α-Glucosidase Inhibitors with Potent In Vivo Antihyperglycemic Activities.

We report the first attempt of double-spot structural modification on a side-chain moiety of sulfonium-type α-glucosidase inhibitors isolated from genus Salacia. A series of sulfonium salts with benzylidene acetal linkage at the C3' and C5' positions were designed and synthesized. In vitro enzyme inhibition evaluation showed that compounds with a strong electron-withdrawing group attached at the ortho position on the phenyl ring present stronger inhibitory activities. Notably, the most potent inhibitor 21b (1.0 mpk) can exhibit excellent hypoglycemic effects in mice, which can still compete with those of acarbose (20.0 mpk). Molecular docking of 21b demonstrated that besides conventional interacting patterns, the newly introduced benzylidene acetal moiety plays an important role in anchoring the whole molecule in a concave pocket of the enzyme. The successful identification of 21b as a lead compound for new drug discovery may provide a means for structure modification and diversification of the distinguished sulfonium-type α-glucosidase inhibitors.

Inhibitory Potential of α-Amylase, α-Glucosidase, and Pancreatic Lipase by a Formulation of Five Plant Extracts: TOTUM-63.

Controlling post-prandial hyperglycemia and hyperlipidemia, particularly by regulating the activity of digestive enzymes, allows managing type 2 diabetes and obesity. The aim of this study was to assess the effects of TOTUM-63, a formulation of five plant extracts (Olea europaea L., Cynara scolymus L., Chrysanthellum indicum subsp. afroamericanum B.L.Turner, Vaccinium myrtillus L., and Piper nigrum L.), on enzymes involved in carbohydrate and lipid absorption. First, in vitro inhibition assays were performed by targeting three enzymes: α-glucosidase, α-amylase, and lipase. Then, kinetic studies and binding affinity determinations by fluorescence spectrum changes and microscale thermophoresis were performed. The in vitro assays showed that TOTUM-63 inhibited all three digestive enzymes, particularly α-glucosidase (IC50 of 13.1 µg/mL). Mechanistic studies on α-glucosidase inhibition by TOTUM-63 and molecular interaction experiments indicated a mixed (full) inhibition mechanism, and higher affinity for α-glucosidase than acarbose, the reference α-glucosidase inhibitor. Lastly, in vivo data using leptin receptor-deficient (db/db) mice, a model of obesity and type 2 diabetes, indicated that TOTUM-63 might prevent the increase in fasting glycemia and glycated hemoglobin (HbA1c) levels over time, compared with the untreated group. These results show that TOTUM-63 is a promising new approach for type 2 diabetes management via α-glucosidase inhibition.

Identification of yeast α-glucosidase inhibitors from Pueraria lobata by ligand fishing based on magnetic mesoporous silicon combined with knock-out/knock-in technology.

In this study, a ligand fishing technique based on magnetic mesoporous silicon was established and used to screen α-glucosidase inhibitors from Pueraria lobata. To clarify quantity-activity relationships in a holistic view, the knock-out/knock-in technology was used to analyse the interactions of several active constituents in P. lobata. Magnetic mesoporous silicon with a large specific surface area and better biocompatibility was synthesised. Subsequently, α-glucosidase was immobilised on -NH2-modified magnetic mesoporous silicon, and the compounds in the crude extract of P. lobata were screened across enzyme binding. The structures of the ligands were elucidated using UPLC-Q-TOF-MS/MS, and their activities were verified by knock-out/knock-in experiments and molecular docking. Daidzein and puerarin showed α-glucosidase inhibitory activities with an IC50 of 0.088 ± 0.003 mg mL-1 and 0.414 ± 0.005 mg mL-1, respectively. Among them, puerarin, which accounted for more than 40% of the total content, showed synergistic effects with other components and was the main contributor to the α-glucosidase inhibitory activity of P. lobata.

Identification, characterization and in vitro activity of hypoglycemic peptides in whey hydrolysates from rubing cheese by-product.

The by-product of Chinese rubing cheese is rich in whey protein. Whey hydrolysates exhibit good hypoglycemic activity, but which specific peptide components are responsible for this effect have not yet been investigated. Herein, the α-glucosidase inhibitory activity of the ultrafiltered fraction (<3 kDa) of rubing cheese whey hydrolysates was evaluated with the inhibition rate of 37.89 %. In addition, peptide identification was conducted using LC-MS/MS, and three peptides YPVEPF, VPYPQ, and LPYPY were identified. Among these, YPVEPF had higher α-glucosidase inhibitory activity (IC50 = 3.52 mg/mL) and interacted with α-glucosidase via hydrogen bonding and hydrophobic forces. YPVEPF was characterized as an amphipathic peptide rich in antiparallel (50.50 %) and random coil (35.20 %) structures, as well as showed good tolerance to gastrointestinal digestion and incubation under the temperature range of 20-80 °C. Notably, YPVEPF activity increased in the presence of Al3+ and Fe3+, as well as within the pH range of 2.0-6.0. Furthermore, YPVEPF had negligible hemolytic activity at a concentration of 1.0 mg/mL, no toxicity at concentrations below 0.5 mg/mL, and significantly promoted glucose consumption in HepG2 cells (p < 0.0001). Collectively, these findings indicate the potential of YPVEPF to be used as a novel hypoglycemic peptide in functional foods.

Probiotic fermented whey-milk beverages: Effect of different probiotic strains on the physicochemical characteristics, biological activity, and bioactive peptides.

The effect of probiotic strains (Lactobacillus acidophilus La-03 (La-03); Lactobacillus acidophilus La-05 (La-05); Bifidobacterium Bb-12 (Bb-12) or Lacticaseibacillus casei-01 (L. casei-01)) on the characteristics of fermented whey-milk beverages during storage (4 °C, 30 days) was evaluated. The products were assessed for biological and antioxidant activities, physicochemical characteristics, and bioactive peptides. Probiotic addition increased α-amylase and α-glucosidase inhibition and antioxidant activities, mainly at 15 days of storage. L. casei-01 showed higher metabolic activity (higher titratable acidity and lower pH values) and the presence of anti-hypertensive peptides, while La-5 and Bb-12 showed higher α-glucosidase inhibition, improvements in the high saturated hypercholesterolemic index, and peptides with ACE-inhibitory, antimicrobial, immunomodulatory, and antioxidant activities. Our findings suggest that probiotic fermented whey-milk beverages may exert antidiabetic and antioxidant properties, being suggested La-5 or Bb-12 as probiotics and 15 days of storage.

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches.

Type II diabetes mellitus (T2DM) is a global health issue with high rate of prevalence. The inhibition of α-glucosidase enzyme has prime importance in the management of T2DM. This study was established to synthesize Schiff bases of 1,3-dipheny urea (3a-y) and to investigate their in vitro anti-diabetic capability via inhibiting α-glucosidase, a key player in the catabolism of carbohydrates. The structures of all compounds were confirmed through various techniques including, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and mass-spectrometry (MS) methods. Interestingly all these compounds displayed potent inhibition IC50 values in range of 2.14-115 µM as compared to acarbose used as control. Additionally, all the compounds were docked at the active site of α-glucosidase to predict their mode of binding. The docking results indicates that Glu277 and Asn350 play important role in the stabilization of these compounds in the active site of enzyme. These molecules showed excellent predicted pharmacokinetics, physicochemical and drug-likeness profile. The anti-diabetic potential of these molecules signifies their medical importance and provide insights into prospective therapeutic options for the treatment of T2DM.

Structure-Based Design of Potent Iminosugar Inhibitors of Endoplasmic Reticulum α-Glucosidase I with Anti-SARS-CoV-2 Activity.

Enveloped viruses depend on the host endoplasmic reticulum (ER) quality control (QC) machinery for proper glycoprotein folding. The endoplasmic reticulum quality control (ERQC) enzyme α-glucosidase I (α-GluI) is an attractive target for developing broad-spectrum antivirals. We synthesized 28 inhibitors designed to interact with all four subsites of the α-GluI active site. These inhibitors are derivatives of the iminosugars 1-deoxynojirimycin (1-DNJ) and valiolamine. Crystal structures of ER α-GluI bound to 25 1-DNJ and three valiolamine derivatives revealed the basis for inhibitory potency. We established the structure-activity relationship (SAR) and used the Site Identification by Ligand Competitive Saturation (SILCS) method to develop a model for predicting α-GluI inhibition. We screened the compounds against SARS-CoV-2 in vitro to identify those with greater antiviral activity than the benchmark α-glucosidase inhibitor UV-4. These host-targeting compounds are candidates for investigation in animal models of SARS-CoV-2 and for testing against other viruses that rely on ERQC for correct glycoprotein folding.

Alkaloids and Styryl lactones from Goniothalamus ridleyi King and Their α-Glucosidase Inhibitory Activity.

Gonioridleylactam (1), a new compound, is a unique dimeric aristolactam isolated from the EtOAc extract of the twigs of Goniothalamus ridleyi King. The structure of gonioridleylactam (1) consists of two different aristolactams linked together with two methylenedioxy bridges at C-3/C-3' and C-4/C-4', generating a ten-membered ring of [1,3,6,8]tetraoxecine. A new natural product, gonioridleyindole (3-hydroxymethyl-1-methyl-1H-benz[f]indole-4,9-dione, 2), together with eight known compounds (3-10) were also isolated from this plant. Their structures were extensively characterized by spectroscopic methods and comparisons were made with the literature. Compounds 1-4, 7, and 9 were evaluated for their α-glucosidase inhibitory activity. Of these, 3,5-demethoxypiperolide (7) displayed the highest α-glucosidase inhibitory activity, with an IC50 value of 1.25 µM.

New Succinimide-Thiazolidinedione Hybrids as Multitarget Antidiabetic Agents: Design, Synthesis, Bioevaluation, and Molecular Modelling Studies.

Diabetes mellitus (DM) is a metabolic disorder majorly arising from the pathophysiology of the pancreas manifested as a decline in the insulin production or the tissue's resistance to the insulin. In this research, we have rationally designed and synthesized new succinimide-thiazolidinedione hybrids for the management of DM. In a multistep reaction, we were able to synthesize five new derivatives (10a-e). All the compounds were new containing a different substitution pattern on the N-atom of the succinimide ring. Initially, all the compounds were tested against the in vitro α-glucosidase, α-amylase, PTP1B, and DPP4 targets. In all of these targets, the compound 10d was observed to be the most potential antidiabetic agent. Based on this, the antidiabetic activity of the compound 10d was further investigated in experimental animals, which overall gave us encouraging results. The molecular docking studies of the compound 10d was also performed against the target enzymes α-glucosidase, α-amylase, PTP1B, and DPP4 using MOE. Overall, we observed that we have explored a new class of compounds as potential antidiabetic agents.

Discovery, Validation, and Target Prediction of Antibacterial and Antidiabetic Components of Archidendron clypearia Based on a Combination of Multiple Analytical Methods.

Archidendron clypearia (A. clypearia), a Fabaceae family member, is widely used as an anti-inflammatory herbal medicine; however, its antibacterial and antidiabetic properties have not been extensively investigated. This study aimed to systematically analyze the antibacterial and antidiabetic components of A. clypearia by utilizing a combination of analytical methods. First, ten different polarity extracts were analyzed through ultra-performance liquid chromatography (UPLC), and their antibacterial and antidiabetic activities were evaluated. Then the spectrum-effect relationship between the biological activity and UPLC chromatograms was analyzed by partial least squares regression and gray relational analysis, followed by corresponding validation using isolated components. Finally, network pharmacology and molecular docking were implemented to predict the main antibacterial target components of A. clypearia and the enzyme inhibition active sites of α-amylase and α-glucosidase. P15, P16, and P20 were found to be the antibacterial and antidiabetic active components. The inhibitory effect of 7-O-galloyltricetiflavan (P15) on six bacterial species may be mediated through the lipid and atherosclerosis pathway, prostate cancer, adherens junctions, and targets such as SRC, MAPK1, and AKT1. The molecular docking results revealed that 7-O-galloyltricetiflavan and 7,4'-di-O-galloyltricetiflavan (P16/P20) can bind to α-amylase and α-glucosidase pockets with binding energies lower than -6 kcal/mol. Our study provides guidance for the development of antibacterial and antidiabetic products based on A. clypearia and can be used as a reference for the evaluation of bioactivity of other herbs.

A Comprehensive Approach to Derivatization: Elemental Composition, Biochemical, and In Silico Studies of Metformin Derivatives Containing Copper and Zinc Complexes.

The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1-MCu9) and Zn II (MZn1-MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives' biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski's rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development.

Polyphenol Profile and In Vitro Antioxidant and Enzyme Inhibitory Activities of Different Solvent Extracts of Highland Barley Bran.

Five different solvent extracts of highland barley bran were analyzed and compared for their polyphenol profile, antioxidant activity, and α-glucosidase and α-amylase inhibitory activities. The highland barley bran acetone extract had the highest total phenolic content, total flavonoid content, and antioxidant capacity. It was followed by the methanol and ethanol extracts, while n-butanol and ethyl acetate extracts exhibited lower measured values. Diosmetin, luteolin, protocatechuic acid, vanillic acid, ferulic acid, phlorogucinol, diosmin, isoquercitrin, catechin, and isovitexin were among the most abundant phenolic compounds identified in different solvent extracts, and their concentrations varied according to the solvent used. The highest α-glucosidase and α-amylase inhibitory activity were observed in the ethyl acetate extract of highland barley bran, followed by the acetone and methanol extracts. In contrast, n-butanol and ethanol extracts exhibited lower measured values. The different solvent extracts were effective inhibitors for α-glucosidase and α-amylase with activity reaching to 34.45-94.32% and 22.08-35.92% of that of positive control acarbose, respectively. There were obvious correlations between the phenolic content and composition of different solvent extracts and their in vitro antioxidant activity, α-glucosidase inhibition activity and α-amylase inhibition activity. Black barley bran is an excellent natural raw material for developing polyphenol-rich functional foods and shows good antioxidant and hypoglycemic potential to benefit human health.