Α-glucosidase Activity Research Articles

Use of Various Sugarcane Byproducts to Produce Lipid Extracts with Bioactive Properties: Physicochemical and Biological Characterization.

Sugarcane, a globally cultivated crop constituting nearly 80% of total sugar production, yields residues from harvesting and sugar production known for their renewable bioactive compounds with health-promoting properties. Despite previous studies, the intricate interplay of extracts from diverse sugarcane byproducts and their biological attributes remains underexplored. This study focused on extracting the lipid fraction from a blend of selected sugarcane byproducts (straw, bagasse, and filter cake) using ethanol. The resulting extract underwent comprehensive characterization, including physicochemical analysis (FT-IR, DSC, particle size distribution, and color) and chemical composition assessment (GC-MS). The biological properties were evaluated through antihypertensive (ACE), anticholesterolemic (HMG-CoA reductase), and antidiabetic (alpha-glucosidase and Dipeptidyl Peptidase-IV) assays, alongside in vitro biocompatibility assessments in Caco-2 and Hep G2 cells. The phytochemicals identified, such as β-sitosterol and 1-octacosanol, likely contribute to the extract's antidiabetic, anticholesterolemic, and antihypertensive potential, given their association with various beneficial bioactivities. The extract exhibited substantial antidiabetic effects, inhibiting α-glucosidase (5-60%) and DPP-IV activity (25-100%), anticholesterolemic potential with HMG-CoA reductase inhibition (11.4-63.2%), and antihypertensive properties through ACE inhibition (24.0-27.3%). These findings lay the groundwork for incorporating these ingredients into the development of food supplements or nutraceuticals, offering potential for preventing and managing metabolic syndrome-associated conditions.

A New Potent Inhibitor against α-Glucosidase Based on an In Vitro Enzymatic Synthesis Approach.

Inhibiting the activity of intestinal α-glucosidase is considered an effective approach for treating type II diabetes mellitus (T2DM). In this study, we employed an in vitro enzymatic synthesis approach to synthesize four derivatives of natural products (NPs) for the discovery of therapeutic drugs for T2DM. Network pharmacology analysis revealed that the betulinic acid derivative P3 exerted its effects in the treatment of T2DM through multiple targets. Neuroactive ligand-receptor interaction and the calcium signaling pathway were identified as key signaling pathways involved in the therapeutic action of compound P3 in T2DM. The results of molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations indicate that compound P3 exhibits a more stable binding interaction and lower binding energy (-41.237 kcal/mol) with α-glucosidase compared to acarbose. In addition, compound P3 demonstrates excellent characteristics in various pharmacokinetic prediction models. Therefore, P3 holds promise as a lead compound for the development of drugs for T2DM and warrants further exploration. Finally, we performed site-directed mutagenesis to achieve targeted synthesis of betulinic acid derivative. This work demonstrates a practical strategy of discovering novel anti-hyperglycemic drugs from derivatives of NPs synthesized through in vitro enzymatic synthesis technology, providing potential insights into compound P3 as a lead compound for anti-hyperglycemic drug development.

A colorimetric sensing strategy based on chitosan-stabilized platinum nanoparticles for quick detection of α-glucosidase activity and inhibitor screening.

α-Glucosidase (α-Glu) is implicated in the progression and pathogenesis of type II diabetes (T2D). In this study, we developed a rapid colorimetric technique using platinum nanoparticles stabilized by chitosan (Ch-PtNPs) to detect α-Glu activity and its inhibitor. The Ch-PtNPs facilitate the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) into oxidized TMB (oxTMB) in the presence of dissolved O2. The catalytic hydrolysis of 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G) by α-Glu produces ascorbic acid (AA), which reduces oxTMB to TMB, leading to the fading of the blue color. However, the presence of α-Glu inhibitors (AGIs) hinders the generation of AA, allowing Ch-PtNPs to re-oxidize colorless TMB back to blue oxTMB. This unique phenomenon enables the colorimetric detection of α-Glu activity and AGIs. The linear range for α-Glu was found to be 0.1-1.0 U mL-1 and the detection limit was 0.026 U mL-1. Additionally, the half-maximal inhibition value (IC50) for acarbose, an α-Glu inhibitor, was calculated to be 0.4769mM. Excitingly, this sensing platform successfully detected α-Glu activity in human serum samples and effectively screened AGIs. These promising findings highlight the potential application of the proposed strategy in clinical diabetes diagnosis and drug discovery.

Preparation of sea buckthorn (Hippophae rhamnoides L.) seed meal peptide by mixed fermentation and its effect on volatile compounds and hypoglycemia.

This study employed mixed bacterial strains to ferment seabuckthorn seed meal into peptides, and conducted a comprehensive evaluation of the growth adaptive conditions, molecular weight distribution, volatile compounds, and in vitro hypoglycemic activity required for fermentation. Results showed that when the amount of maltose was 1.1% and MgSO4·7H2O was added at 0.15 g/L, the peptide yield reached 43.85% with a mixed fermentation of Lactobacillus fermentum, Bacillus subtilis, Lactobacillus casei, Lactobacillus rhamnosus, and Lactobacillus acidophilus. Components with a molecular weight below 1 kDa were found to be more effective in inhibiting the activity of α-amylase and α-glucosidase, with the identified sequence being FYLPKM. Finally, SPME/GC-MS results showed that 86 volatile components were detected during the fermentation of seabuckthorn seed meal, including 22 alcohols, 9 acids, 7 ketones, 14 alkanes, 20 esters, and 14 other compounds. With prolonged fermentation time, the content of acids and esters increased significantly.

Dominant lignan profiles and antidiabetic activity of thermally treated and non-treated burdock seeds

Burdock seeds (Fructus arctii) are used as a traditional medicine for cough, inflammation, detoxification, cancer and diabetes, usually as decoction obtained with seeds subjected to thermal pre-treatment. The present work aimed to perform the phytochemical characterization of the stir-baked and non-baked seeds of various Arctium lappa populations from nine localities. Arctiin was dominant compound in non-baked seeds ranging from 40.6–92.6 mg/g. Thermal treatment resulted in a significant transformation of phenolic compounds and arctigenin was prevalent in the baked samples with the content from 25.2–57.4 mg/g. The antidiabetic potential of baked and non-baked burdock seed extracts was further evaluated in vitro by inhibition of α-amylase and α-glucosidase activity, while molecular docking analysis was used to reveal the main molecular interactions underlying the inhibitory effects on these enzymes. In vitro study showed that stir-baked burdock seed extracts were stronger inhibitors of both enzymes compared to non-baked. The several extracts showed strong inhibition of both enzymes by almost or more than 60%, which was lower compared to acarbose (82.99% at a concentration of 1 mg/mL). Arctin and arctigenin were individually significantly stronger inhibitors of α-amylase and particularly α-glucosidase compared to burdock extracts and acarbose, and their activity was concentration dependent. Moreover, antidiabetic activity for the most active sample was determined in vivo using animals on high-fat and sucrose diet, where promising results were obtained. Briefly, after three months of administration of the stir-baked seed extract (100 mg/kg body weight), complete recovery from a hyperglycemic state was achieved. According to the obtained results A. lappa stir-baked seed extract is a potential drug with hypoglycemic action as indicated by in vitro, in vivo and in silico studies.

Undescribed Triterpenes from the Leaves of Syzygium myrsinifolium with Their α-Glucosidase and α-Amylase Inhibition Activity.

Two undescribed triterpenes, syzyfolium A (1) and syzyfolium B (2), together with twelve known compounds, terminolic acid (3), actinidic acid (4), piscidinol A (5), threo-dihydroxydehydrodiconiferyl alcohol (6), lariciresinol-4-O-β-D-glucoside (7), icariol A2 (8), 14β,15β-dihydroxyklaineanone (9), garcimangosone D (10), (+)-catechin (11), myricetin-3-O-α-L-rhamnopyranoside (12), quercitrin (13), and 3, 4, 5-trimethoxyphenyl-(6'-O-galloyl)-O-β-D-glucopyranoside (14) were isolated from the leaves of Syzygium myrsinifolium. Their chemical structures were determined by IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 3 and 4 inhibited significantly α-glucosidase with IC50 values of 23.99 and 36.84, respectively, and compounds 1 and 2 inhibited significantly α-amylase with IC50 values of 35.48 and 43.65 μM, respectively.

Polyphenol-rich extract of Chinese sumac (Rhus chinensis Mill.) fruits and its main component decrease in vitro starch digestibility of bread: Exploring the potential mechanisms from the perspective of molecular interactions

This study intended to examine whether the polyphenol-rich extract of Chinese sumac fruits (PREF) and its main component quercitrin can delay the in vitro starch digestibility of bread and unravel the underlying mechanisms. The findings indicated that PREF or quercitrin fortification, especially a high dose of PREF (50 g/kg of flour), altered the texture and surface morphology of bread and reduced its digestibility. In vitro inhibiting starch digesting enzymes and in silico analyses were performed to unveil the underlying mechanisms. Both PREF and quercitrin significantly inhibited the activities of α-glucosidase and α-amylase, which could be attributed to the fact that quercitrin can effectively enter the active site of enzymes and form a stable complex. Moreover, the major polyphenols in PREF formed a stable complex with the starch chain, which reduced its digestibility. These encouraging results signify that PREF fortification may be used to develop new healthy bread products for patients with diabetes.

Probiotic Yogurt Supplemented with Lactococcus lactis R7 and Red Guava Extract: Bioaccessibility of Phenolic Compounds and Influence in Antioxidant Activity and Action of Alpha-amylase and Alpha-glucosidase Enzymes.

The industry has increasingly explored the development of foods with functional properties, where supplementation with probiotics and bioactive compounds has gained prominence. In this context, the study aimed to evaluate the influence of in vitro biological digestion on the content of phenolic compounds, antioxidant activity, and inhibition of α-amylase and α-glucosidase activities of probiotic yogurt supplemented with the lactic acid bacteria Lactococcus lactis R7 and red guava extract (Psidium cattleianum). A yogurt containing L. lactis R7 (0.1%) and red guava extract (4%) was characterized for the content of phenolic compounds, antioxidant activity, and potential for inhibition of digestive enzymes after a simulated in vitro digestion process. After digestion, the caffeic and hydroxybenzoic acids remained, and sinapic acid only in the last digestive phase. Antioxidant activity decreased during digestion by 28.93, 53.60, and 27.97% for DPPH, nitric oxide and hydroxyl radicals, respectively, and the inhibition of the α-amylase enzyme decreased only 4.01% after the digestion process. α-glucosidase was more efficient in intestinal digestion, demonstrating an increase of almost 50% in probiotic yogurt with red guava extract before digestion. Possibly, the phenolics change their conformation during digestion, generating new compounds, reducing antioxidant activity, and increasing the inhibitory activity of α-glucosidase digestive enzymes. It was concluded that the probiotic yogurt formulation supplemented with red guava extract could interfere with the concentration of phenolic compounds and the formation of new compounds, suggesting a positive and effective inhibition of the digestive enzymes, even after the digestive process.

Unleashing the potential of short-chain fatty acids: Alginate-degrading consortium boosts anaerobic sludge fermentation

To enhance the production of short-chain fatty acids (SCFAs) from waste activated sludge (WAS), we introduced an alginate-degrading microbial consortium (ADC) and investigated its impact across different dosage levels on anaerobic WAS fermentation. At ADC dosages of 5%, 10%, and 20% (v/v), the soluble chemical oxygen demand (SCOD) content increased by 0.99-fold, 1.19-fold, and 1.78-fold, respectively, compared to the control. Concurrently, there was a substantial rise in the acetate ratio from 34.11% to 63.70%− 66.6%. Following ADC supplementation, the activities of protease and α-glucosidase were significantly enhanced, and hydrophobicity markedly reduced, facilitating the release of organic compounds from WAS. Microbial analysis pinpointed Tetrasphaera, Tessaracoccus, Brooklawnia, and Bacteroidetes_vadinHA17 as primary contributors to the hydrolysis of polysaccharide fraction. Metabolic analysis unveiled an overexpression of functional metabolisms in the ADC groups, which promoted the increased utilization of proteins, amino acids, and other macromolecular organics, thereby stimulating ammonia emission and SCFAs production.

In Vitro Inhibitory Effects of Some Antiviral, Antidiabetic, and Non-Steroidal Anti-Inflammatory Drug Active Compounds on α-Glucosidase and Myeloperoxidase Activities

In recent decades, interest in enzyme inhibition, such as myeloperoxidase (MPO) and glycosidases, has dramatically increased, mainly because these enzymes play a vital role in many biological processes. Based on the biological potential associated with these enzymes, instead of several glycosidase and myeloperoxidase (MPO) inhibitors that have been developed, there are not enough studies on the inhibition effects of widely used types of antivirals (aciclovir, tenofovir), oral antidiabetics (glibenclamide, glibornuride, glurenorm, met-formin), and non-steroidal anti-inflammatory drugs (NSAIDs) active substances (benzydamine HCl, diclofenac, indomethacin, ketorolac tromethamine, paracetamol, salicylic acid) today. For that reason, the aim of our study is to investigate the inhibition effects of these 12 different drug active substances on α-glucosidase and MPO activities. According to the obtained results, the screened drug active substances acyclovir, glibornuride, and paracetamol inhibited α-glucosidase with the lowest IC50 value, while similarly low values for MPO were found by tenofavir, glurenorm, and indomethacin. In our study, we can suggest that these active pharmaceu-tical ingredients may contribute to the pharmaceutical industry due to their inhibitory effects on α-glucosidase and MPO in vitro.

In vitro α-amylase/α-glucosidase, cytotoxicity and radical scavenging potential of Hypoxishemerocallidea synthesized magnesium oxide nanoparticles

The prevalence of diabetes has continued to increase over the past decade. Medicinal extract-synthesized nanoformulations incorporating trace elements found in the body have emerged as alternative therapeutic technology for the treatment of diabetes. In this study, magnesium oxide (MgO) nanoparticles were prepared using Hypoxishemerocallidea (HH) and investigated for their cytotoxicity, antioxidant, and antidiabetic potentials. MgO NPs were characterized by transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, and zeta-potential techniques. TEM analysis confirmed the 2D nanosheet-like morphology of the nanoparticles with particle size (diameter; 300 nm and length of about 1 µm) while the FTIR spectra showed functional groups correlating to the bioactive compounds of HH in the MgO NPs. Moderate antioxidant activity of MgO NPs was observed against DPPH (IC50 = 57.35 ± 0.28 µg/mL) and ABTS (IC50 = 52.08 ± 0.24 µg/mL). The nanoparticles were shown to be less toxic to normal embryonic (HEK293) and human liver (HEPG2) cell lines, with IC50 of 48.63 ± 0.73 and 32.39 ± 0.95 µg/mL, respectively compared to a known cytotoxic drug, doxorubicin which exhibited IC50 of 2.70 ± 0.32 and 8.62 ± 0.57 µg/mL respectively. Besides, the anti-hyperglycemic potential of the MgO NPs as demonstrated by α-amylase and α-glucosidase activities were significantly high with IC50 values of 33.03 ± 1.43 and 52.38 ± 3.06 µg/mL, respectively. These results were compared with an FDA-approved antidiabetic reference standard Acarbose, which exhibited IC50 values of 24.54 ± 1.55 and 6.54 ± 0.27 µg/mL. The results indicated that the HH bioinspired MgO NPs are capable of inhibiting meditators of diabetes and oxidative stress. This study further suggests that the MgO NPs synthesized using HH could be a good candidate for the management of diabetes and other inflammatory diseases due to their strong enzyme inhibition, efficient antioxidant properties, and biocompatibility.

Smartphone-assisted ratiometric fluorescence sensor for sensitive and portable α-glucosidase activity detection and inhibitor screening

α-Glucosidase (α-Glu) is an enzyme that plays an essential role in the digestion of carbohydrates, and its activity detection and inhibitor screening are crucial for the therapy of diseases and development of new drugs. In this study, α-Glu can catalyze the hydrolysis of α-arbutin to produce hydroquinone (HQ), and HQ can regulate the in-situ synthesis of polymer carbon dots (PCDs) with ethylenediamine (EDA). PCDs and tetraphenylporphyrin tetrasulphonic acid (TPPS) are separately designed as green and red fluorescent sensing units. With the increase of α-Glu concentration, the number of PCDs is gradually increased, resulting in enhancement of green fluorescence and quenching of red fluorescence. Conversely, when α-Glu inhibitors (AGIs) are present, the activity of α-Glu is inhibited, leading to weak green fluorescence and strong red fluorescence. Thus a ratiometric fluorescence sensor was designed for the determination of α-Glu activity and screening of AGIs. The developed ratiometric sensor exhibits a linear relationship between fluorescence intensity ratios and α-Glu concentrations (0.01 to 0.04 U/mL) with limit of detection of 0.184 mU/mL, which is much lower than the single fluorescence model. In addition, rapid and portable detection of α-Glu can be achieved using a smartphone with a color picking software installed as a signal detection device, which greatly reduces the cost and time of detection and provides a promising method for qualitative identification and quantitative analysis of α-Glu in the resource-limited areas. Moreover, the method is very promising for high-throughput screening AGIs from natural products.

Inhibitory mechanism of chrysin and diosmetin to α-glucosidase: insights from kinetics, multispectroscopy and molecular docking investigations

Inhibition of α-glucosidase activity is a promising method to prevent postprandial hyperglycemia. The inhibitory effect and interaction of chrysin and diosmetin on α-glucosidase were studied in this study. The results of inhibition kinetics showed that chrysin and diosmetin reversibly inhibited α-glucosidase activity with IC50 value of 26.445 ± 1.406 μmol L−1 and 18.380 ± 1.264 μmol L−1, respectively. Further research revealed that chrysin exhibited a mixed-type inhibitory pattern against α-glucosidase, while diosmetin was noncompetitive inhibitory with Ki value of (2.6 ± 0.04) ×10−4 mol L−1. Fluorescence spectroscopy showed that both chrysin and diosmetin could quench the intrinsic fluorescence of α-glucosidase, the maximum emission wavelength of tyrosine (Tyr) and tryptophan (Trp) were not moved by chrysin, but red shifted by diosmetin. UV-Vis, fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) measurements showed that the secondary structure and microenvironment of α-glucosidase were changed by chrysin and diosmetin. Further analysis of molecular docking showed that chrysin and diosmetin could bind with α-glucosidase and might cause the decrease of α-glucosidase activity. The results of molecular dynamics (MD) simulation showed that the stability of chrysin (or diosmetin)-α-glucosidase complex system was changed during binding process. In conclusion, chrysin and diosmetin are good α-glucosidase inhibitors. Communicated by Ramaswamy H. Sarma

In vitro study on antioxidant and lipid-lowering activities of tobacco polysaccharides

Tobacco polysaccharides were extracted by hot water extraction, and purified and separated using DEAE-52 cellulose chromatography columns, and three purified polysaccharide fractions, YCT-1, YCT-2, and YCT-3, were finally obtained. The physicochemical properties of the three fractions were analyzed by ultraviolet spectroscopy, high-performance liquid chromatography and high-performance gel chromatography. The in vitro antioxidant activity of tobacco polysaccharides was compared among different fractions by using DPPH radical, hydroxyl radical scavenging assay and potassium ferricyanide method. The in vitro hypoglycemic activity was compared using α-amylase and α-glucosidase activity inhibition assay. And the in vitro hypolipidemic activity were investigated by using pancreatic lipase activity inhibition assay and HepG-2 intracellular lipid accumulation assay. All the results showed that the constituent monosaccharides of the three tobacco polysaccharide fractions were similar, but the molar percentages of each monosaccharide were different. The average molecular weights of the three components were 27,727 Da, 27,587 Da, and 66,517 Da, respectively, and the scavenging activities on DPPH radicals and hydroxyl radicals were at a high level with good quantitative-effect relationships. The reducing power were much lower than that of the positive control VC, and the three polysaccharide fractions had a weak inhibitory ability on α-amylase activity, but showed excellent inhibitory ability on α-glucosidase and pancreatic lipase activity. In addition, the results of cellular experiments showed that all three fractions were able to inhibit lipid over-accumulation in HepG-2 cells by increasing the mRNA expression levels of PPAR-α, CPT-1A, and CYP7A1 genes, and the tobacco polysaccharide YCT-3 showed the best effect. The mechanism by which YCT-3 ameliorated the over-accumulation of intracellular lipids in HepG-2 cells was found to be related to its influence on the expression of miR-155-3p and miR-17-3p in the exosomes of HepG-2 cells.Graphical

Multienzyme cascades analysis of α-glucosidase by oxygen deficient MoO3-x

BackgroundRecently, the enzymatic cascade reactions during the cellular process are widely used for fabricating robust biosensors and they have attracted extensive attention in analyzing various clinical biomarkers. The enzymatic cascades analysis is commonly based on the peroxidase (POD)/oxidase coupled system. However, the requirement of harsh acidic environment, poor stability and interference from the oxidase further limit their analytical practicability. Herein, novel chromogenic nanomaterials with H2O2 sensitive features are urgently required to replace the POD nanozyme in enzymatic cascades based bioanalysis. ResultsHerein, oxygen deficient MoO3-x with H2O2 sensitive features and near-infrared (NIR) absorption band have been ultra-fast synthesized and utilized for the enzymatic cascades analysis of α-Glucosidase's activity, and inhibitors screening. With the addition of 4-nitrophenyl-α-d-glucopyranoside, the simultaneous presence of α-Glucosidase and glucose oxidase (GOx) would fade their dark blue color and decrease the NIR absorption. The α-Glucosidase's activity can be analyzed by the absorption at 770 nm, and their limit of detection is 8 × 10−5 U/mL, indicating the superior performance of the proposed colorimetric assay. Moreover, this proposed α-Glucosidase assay is further utilized for inhibitors screening. Moreover, the activity of α-Glucosidase can also be analyzed by the smartphone and microplate reader through the agarose-based colorimetric portable kit. SignificanceThis MoO3-x involved enzymatic cascades assay would facilitate for the development of bio-analysis related to H2O2 generation or consumption. Moreover, this bio-analysis strategy will contribute to the development of other H2O2 sensitive chromogenic nanomaterials for the analysis of certain biomolecules and biological enzymes.

Identification of the characteristic chemical constituents in fermented Toona sinensis buds and exploration of their hypoglycemic efficacy by widely targeted metabolomics

Toona sinensis is a unique perennial deciduous tree in China, and its buds are popular vegetables with unique flavors and high nutritional value. In this study, we produced fermented T. sinensis buds using a commercial strain of Lactiplantibacillus plantarum and utilized widely targeted metabolomics to investigate the effect of each Lactobacillus fermentation method on the metabolite composition of fermented T. sinensis buds. Multivariate analysis revealed a significant difference in the metabolic profile between each fermented T. sinensis bud group and the control group. The metabolite profiles of T. sinensis buds fermented for 48 h and 68 h were similar, but both differed significantly from the metabolite profiles of T. sinensis buds fermented for 0 h. Compared with the control group, the T. sinensis buds fermented for 48 h and 68 h had high levels of flavonoids, alkaloids and lipids. In addition, the hypoglycemia test data showed that fermentation significantly increased the ability of T. sinensis buds to inhibit α-amylase and α-glucosidase activities, and the extract of fermented T. sinensis buds significantly improved glucose uptake by IR-HepG2 cells. This study suggests that metabolomics is an effective approach for revealing the differences in metabolite profiles in T. sinensis buds fermented for different durations and is useful for clarifying the mechanism by which fermented T. sinensis buds enhance hypoglycemic activity.

Luminescent solid-state carbon dots synthesized based on the one-step hydrothermal method for the immobilization of α-glucosidase and imaging screening of enzyme inhibitors

Modern pharmacology studies have demonstrated that α-glucosidase is closely associated with a variety of metabolic disorders. Natural herbs have emerged as possible sources of α-glucosidase inhibitors (AGIs) in recent years. Thus far, highly selective screening of biologically active chemicals in complicated mixtures using ligand fishing approaches has not been able to achieve biomedical imaging, which is critical for real-time identification. Hence, this paper presented a novel technique for screening potential AGIs in Scutellaria baicalensis by utilizing fluorescent carbon dots that have been immobilized with α-glucosidase (α-glu-NH2-CDs). The synthesized carbon dots materials exhibited excellent fluorescence properties, biocompatibility, and an abundance of functional groups, as demonstrated by the utilization of several techniques. The activity of α-glucosidase covalently linked to the material under ideal immobilization conditions was 86.81% of that of the free form. The immobilized α-glucosidase also exhibited great temperature stability, pH stability and reusability according to an examination of its enzymatic characteristics. As a result, three ligands were identified as potential AGIs, i.e., baicalein, wogonin and scullcapflavone II by UPLC-MS/MS. The molecular docking and enzyme inhibition test indicated that the isolated compounds exhibited significant α-glucosidase inhibitory activities. Moreover, the proliferation inhibitory activity of the screened ligands on HCT-116 cells was further verified morphologically using in situ imaging technique. These results strongly suggested that the established method, which combined ligand fishing with in situ visual imaging, not only screen and separate the potential AGIs in Scutellaria baicalensis quickly and effectively, but also provide an effective platform for screening bioactive compounds on different receptors.

Analysis of Polyphenol Extract from Hazel Leaf and Ameliorative Efficacy and Mechanism against Hyperuricemia Zebrafish Model via Network Pharmacology and Molecular Docking.

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.

Alpha-glucosidase inhibitory and hypoglycemic effects of imidazole-bearing thioquinoline derivatives with different substituents: In silico, in vitro, and in vivo evaluations

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels. It was shown that modulating the activity of α-glucosidase, an enzyme involved in carbohydrate digestion and absorption, can improve blood sugar control and overall metabolic health in individuals with T2DM. As a result, in the current study, a series of imidazole bearing different substituted thioquinolines were designed and synthesized as α-glucosidase inhibitors. All derivatives exhibited significantly better potency (IC50 = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with Ki = 9.66 µM. Also, the most potent derivative was subjected to molecular docking and molecular dynamic simulation against α-glucosidase to determine its mode of action in the enzyme and study the complex's behavior over time. In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. Additionally, in a diabetic rat model, treatment with 8g significantly reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose, a standard drug used for blood sugar control. The findings suggest that the synthesized compound 8g holds promise as an α-glucosidase inhibitor for improving blood sugar control and metabolic health.

In vitro α-amylase and α-glucosidase inhibition study of dihydropyrimidinones synthesized via one-pot Biginelli reaction in the presence of a green catalyst

A green catalyst WELPSA-catalyzed three-component condensation (Biginelli) process involving an aldehyde, barbituric/thiobarbituric/1,3-dimethylbarbituric acid, and urea/thiourea/guanidine hydrochloride in a single pot in presence of a green solvent for the production of DHPM have been presented. The catalyst is reusable and this methodology is scalable. By using the in vitro experiments, the antidiabetic potentiality of synthesized compounds that inhibit α-amylase along with α-glucosidase efficiencies was assessed. All the synthesized compounds except for 4a and 4e, showed the most significant inhibition for α-amylase and α-glucosidase activities. Among the synthesized DHPM compounds, 4c and 4b exhibited significant inhibition profiles compared to the standard antidiabetic drug acarbose. Furthermore, synthesized substances' energy-minimized structures, 3D structures, and DFT calculations were performed using Gaussian 09 software, hybrid models, and MM2 force approaches. Strong hydrogen bonds with amino acid residues Arg-672, Arg-600, Trp-613, Asp-404, Asp-282, and Asp-616 indicate that an α-glucosidase-inhibitory peptide may have hypoglycemic efficacy confirmed by the molecular docking study of the synthesized DHPM.