The α-amylase and α-glucosidase inhibitory activities of the dichloromethane extracts and constituents of Ferulago bracteata roots

Context: Ferulago (Apiaceae) species have been used since ancient times for the treatment of intestinal worms, hemorrhoids, and as a tonic, digestive, aphrodisiac, or sedative, as well as in salads or as a spice due to their special odors.

Objectives: This study reports the α-amylase and α-glucosidase inhibitory activities of dichloromethane extract and bioactive compounds isolated from Ferulago bracteata Boiss. &; Hausskn. roots.

Materials and methods: The isolated compounds obtained from dichloromethane extract of Ferulago bracteata roots through bioassay-guided fractionation and isolation process were evaluated for their in vitro α-amylase and α-glucosidase inhibitory activities at 5000–400?µg/mL concentrations. Compound structures were elucidated by detailed analyses (NMR and MS).

Results: A new coumarin, peucedanol-2′-benzoate (1), along with nine known ones, osthole (2), imperatorin (3), bergapten (4), prantschimgin (5), grandivitinol (6), suberosin (7), xanthotoxin (8), felamidin (9), umbelliferone (10), and a sterol mixture consisted of stigmasterol (11), β-sitosterol (12) was isolated from the roots of F. bracteata. Felamidin and suberosin showed significant α-glucosidase inhibitory activity (IC₅₀ 0.42 and 0.89?mg/mL, respectively) when compared to the reference standard acarbose (IC₅₀ 4.95?mg/mL). However, none of the tested extracts were found to be active on α-amylase inhibition.

Discussion and conclusions: The present study demonstrated that among the compounds isolated from CH₂Cl₂ fraction of F. bracteata roots, coumarins were determined as the main chemical constituents of this fraction. This is the first report on isolation and characterization of the bioactive compounds from root extracts of F. bracteata and on their α-amylase and α-glucosidase inhibitory activities.     

Inhibitory activity of α-amylase and α-glucosidase by plant extracts from the Brazilian cerrado

Diabetes mellitus is the most common disease in the world. One therapeutic approach for treating diabetes is inhibition of α-amylase and α-glucosidase activities to reduce postprandial blood glucose levels. In vitro tests showed that several plant extracts from Brazilian cerrado species can inhibit the activity of α-amylase and α-glucosidase. The extracts of Eugenia dysenterica, Stryphnodendron adstringens, Pouteria caimito, Pouteria ramiflora, and Pouteria torta showed strong α-amylase and α-glucosidase inhibitory activity. Eugenia dysenterica, P. caimito, P. ramiflora, and P. torta aqueous extracts exerted the highest activity against α-amylase (IC??) values of 14.93, 13.6, 7.08, and 5.67 μg/mL, respectively) and α-glucosidase (IC?? values of 0.46, 2.58, 0.35, and 0.22 μg/mL, respectively). Stryphnodendron adstringens ethanol extract also exhibited inhibitory activity against both enzymes (IC??) 1.86 μg/mL against α-amylase and 0.61 μg/mL against α-glucosidase). The results suggest that the activity of these cerrado plants on α-amylase and α-glucosidase represents a potential tool for development of new strategies for treatment of diabetes.     

Rapid investigation of α-glucosidase inhibitory activity of Phaleria macrocarpa extracts using FTIR-ATR based fingerprinting

Phaleria macrocarpa, known as “Mahkota Dewa”, is a widely used medicinal plant in Malaysia. This study focused on the characterization of α-glucosidase inhibitory activity of P. macrocarpa extracts using Fourier transform infrared spectroscopy (FTIR)-based metabolomics. P. macrocarpa and its extracts contain thousands of compounds having synergistic effect. Generally, their variability exists, and there are many active components in meager amounts. Thus, the conventional measurement methods of a single component for the quality control are time consuming, laborious, expensive, and unreliable. It is of great interest to develop a rapid prediction method for herbal quality control to investigate the α-glucosidase inhibitory activity of P. macrocarpa by multicomponent analyses. In this study, a rapid and simple analytical method was developed using FTIR spectroscopy-based fingerprinting. A total of 36 extracts of different ethanol concentrations were prepared and tested on inhibitory potential and fingerprinted using FTIR spectroscopy, coupled with chemometrics of orthogonal partial least square (OPLS) at the 4000–400 cm⁻¹ frequency region and resolution of 4 cm⁻¹. The OPLS model generated the highest regression coefficient with R²Y = 0.98 and Q²Y = 0.70, lowest root mean square error estimation = 17.17, and root mean square error of cross validation = 57.29. A five-component (1+4+0) predictive model was build up to correlate FTIR spectra with activity, and the responsible functional groups, such as –CH, –NH, –COOH, and –OH, were identified for the bioactivity. A successful multivariate model was constructed using FTIR-attenuated total reflection as a simple and rapid technique to predict the inhibitory activity.     

In vitro α-amylase and pancreatic lipase inhibitory activity of Cornus mas L. and Cornus alba L. fruit extracts

Less-common fruits from Cornus spp. (Cornaceae), also named dogwoods, have shown antidiabetic, antibacterial and anti-allergic properties and are thus considered a source of phytochemicals that are beneficial to human health. The study aimed to compare the chemical compositions of the aqueous and ethanolic extracts of lyophilized fresh-picked and commercially available dried fruits of Cornus mas (Cm, cornelian cherry) and Cornus alba (Ca) fruits using HPLC-DAD-MS/MS method. Simultaneously, the α-amylase and pancreatic lipase (PL) inhibitory activities of the prepared extracts were compared by in vitro fluorescence assay based on the kinetic hydrolysis of starch or oleate ester of 4-methylumbelliferone (MUO), respectively. Additionally, a bio-assay guided identification of compounds potentially responsible for the inhibition of pancreatic enzymes was performed. Iridoids (loganic acid, cornuside) and anthocyanins (pelargonidin 3-O-galactoside) were identified in the Cm fruit extracts. Flavonoids, such as quercetin and kaempferol derivatives, were detected in the Ca fruit extracts. The chromatographic separation of the constituents of Ca fruit provided a fraction containing phenolic acids derivatives, which inhibited PL activity by 69.9 ± 4.5% at a concentration of 7.5 μg·mL^?1. The IC₅₀ of hydroxytyrosol glucoside, isolated from the most active Ca fraction, was 0.99 ± 0.10 mg·mL^?1 indicating other constituents responsible for the fraction activity. The most active subfraction from Cm fruit (7.5 μg·mL^?1), which inhibited PL activity by 28.3 ± 1.5%, contained pelargonidin 3-O-galactoside. Loganic acid and cornuside in highly pure form did not inhibit lipase activity. The phytochemical constituents of Cm, and particularly of Ca fruit extracts, can inhibit pancreatic enzymes and thus might be considered effective preparations in the prevention and control of hyperlipidemia related diseases.     

Inhibitors of α-glucosidase and α-amylase from Cyperus rotundus

Context: A methanol extract of Cyperus rotundus L. (Cyperaceae) rhizomes showed inhibitory activity against α-glucosidase and α-amylase, two enzymes involve in carbohydrate digestion.

Objective: Identification of compounds from C. rotundus rhizomes responsible for the inhibition of α-glucosidase and α-amylase.

Materials and methods: Compounds were identified by a phytochemical investigation using combined chromatographic and spectroscopic methods. α-glucosidase and α-amylase inhibitory activities were evaluated by in vitro enzyme inhibition assays.

Results: A new (2RS,3SR)-3,4′,5,6,7,8-hexahydroxyflavane (1), together with three known stilbene dimers cassigarol E (2), scirpusin A (3) and B (4) were isolated. Compound 2 inhibited both α-glucosidase and α-amylase activities while the flavane 1 only showed effect on α-amylase, and compounds 3 and 4 were active on α-glucosidase. All four compounds showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity.

Discussion: The inhibitory activities against α-amylase and α-glucosidase of the C. rotundus rhizomes were reported for the first time. Stilbene dimers are considered as potent inhibitors of α-glucosidase and promising antihyperglycemic agents.

Conclusion: The isolated compounds may contribute to the antidiabetic property of C. rotundus.     

Antioxidant and α-glucosidase inhibitory activities of Achillea tenorii

Abstract

Context: There is a need for the discovery of novel natural remedies to prevent and treat metabolic disorders such as hyperglycemia, type II non-insulin-dependent diabetes mellitus, and obesity. Several Achillea species have been utilized for centuries all around the world and are generally considered effective as hypoglycemic.

Objective: Considering the ethnobotanical uses of Achillea genus, we evaluated the in vitro inhibitory activity of Achillea tenorii Grande (Asteraceae) extract on α-glucosidase, which is a valuable target to prevent and treat metabolic disorders. We also tested its antioxidant activity. Moreover, the phytochemical profile was discussed from a chemotaxonomic point of view.

Materials and methods: In vitro α-glucosidase inhibition of crude ethanolic extract obtained from the aerial parts was assayed as well as the in vitro antioxidant activity (ABTS, DPPH, and FRAP-FZ tests) was measured. The extract was characterized from a phytochemical point of view by means of spectroscopic analysis.

Results: The extract results endowed with α-glucosidase inhibitory activity (IC₅₀ 32?µg/mL) with a particular mechanism of action definable as un-competitive, which differed from the mechanism observed for the best-known α-glucosidase inhibitor (acarbose and miglitol). In addition, a considerable antioxidant potential has been found for A. tenorii extract, which resulted mainly constituted by phenolic compounds such as caffeoylquinic acids and flavonoids.

Discussion and conclusions: These results suggest the potential of A. tenorii as a possible natural remedy to prevent and treat metabolic disorders of carbohydrates.     

New steroids from Anemarrhena asphodeloides rhizome and their α-glucosidase inhibitory activity

Two new steroids were isolated from acid hydrolysis residue of the rhizomes of Anemarrhena asphodeloides. Their structures were identified on the basis of several spectroscopic analysis approaches including 1D, 2D-NMR techniques, and MS data, and by the comparison of spectral data of the known compounds. The biological activities of these two isolated compounds were explored on α-glucosidase. Compound 1 displayed 4.7 folds inhibitory activity against α-glucosidase compared with the positive control acarbose.     

Two new phragmalin-type limonoids from Chukrasia tabularis and their α-glucosidase inhibitory activity

Phytochemical investigation on the stems of C. tabularis (Meliaceae) led to the isolation of two new phragmalin-type limonoids, named tabularisins S and T (1–2), along with five known ones (3–7). The structures of the new limonoids were established by spectroscopic methods including UV, IR, HRESIMS, and 1D and 2D NMR. All the compounds were evaluated for α-glucosidase inhibitory activity in vitro. Compounds 2 and 3 exhibited significant inhibitory activity against α-glucosidase with IC₅₀ values of 0.15 and 0.03 mM, respectively (acarbose as positive control, IC₅₀ 0.95 mM).     

Constituents from the testas of Castanea mollissima Blume with α-glucosidase inhibitory activity

In the screening of biologically active constituents from medicinal plants, the 75% EtOH extract of the testas of Castanea mollissima Blume showed potent α-glucosidase inhibitory activity. By means of various chromatographic methods, the extract gave a new dammarane-type triterpene 1 along with 17 known compounds. The structure of 1 was determined to be 3β-acetoxy-20-oxo-21-nordammaran-23-oic acid by HRMS and NMR studies including 2D NMR experiments. The new compound and some known compounds showed potent α-glucosidase inhibitory activity with acarbose as a positive control.     

Antioxidant and α-amylase inhibitory activities of extract and isolates from Zygogynum pancheri subsp. arrhantum

One new sesquiterpenoid (5R^*,8R^*,9R^*,10R^*)-cinnamolide (8), and seven known compounds, 5-hydroxy-7-methoxyflavonone (1), 8-hydroxy-3-(4′-hydroxyphenyl)-6,7-(2″,2″-dimethylchromene)-tetralone (2), 8-hydroxy-3-(3′,4′-dihydroxyphenyl)-6,7-(2″,2″-dimethylchromene)-tetralone (3), 1β-E-O-p-methoxycinnamoyl-bemadienolide (4), 1β-O-(E-cinnamoyl)-6α-hydroxy-9-epi-polygodial (5), 1β-O-(E-cinnamoyl)-6α-hydroxypolygodial (6), and 1β-O-E-cinnamoylpolygodial (7) were isolated from the ethyl acetate extract of barks of Zygogynum pancheri subsp. arrhantum (Winteraceae). The structures of these molecules were assigned predominantly based on spectral data. The structure of compound 8 was confirmed by X-ray crystallographic analysis. Compounds 2 and 3 exhibited significant antioxidant activity, whereas compounds 1 and 4–7 showed significant α-amylase inhibitory activity.     

In vitro α-glucosidase inhibitory activity of phenolic constituents from aerial parts of Polygonum hyrcanicum

Background and the purpose of the study

The early stage of diabetes mellitus type 2 is associated with postprandial hyperglycemia. Hyperglycemia is believed to increase the production of free radicals and reactive oxygen species, leading to oxidative tissue damage. In an effort of identifying herbal drugs which may become useful in the prevention or mitigation of diabetes, biochemical activities of Polygonum hyrcanicum and its constituents were studied.

Methods

Hexane, ethylacetate and methanol extracts of P. hyrcanicum were tested for α-glucosidase inhibitory, antioxidant and radical scavenging properties. Active constituents were isolated and identified from the methanolic extract in an activity guided approach.

Results

A methanolic extract from flowering aerial parts of the plant showed notable α-glucosidase inhibitory activity (IC₅₀ = 15 μg/ml). Thirteen phenolic compounds involving a cinnamoylphenethyl amide, two flavans, and ten flavonols and flavonol 3-O-glycosides were subsequently isolated from the extract. All constituents showed inhibitory activities while compounds 3, 8 and 11 (IC₅₀ = 0.3, 1.0, and 0.6 μM, respectively) were the most potent ones. The methanol extract also showed antioxidant activities in DPPH (IC₅₀ = 76 μg/ml) and FRAP assays (1.4 mmol ferrous ion equivalent/g extract). A total phenol content of 130 mg/g of the extract was determined by Folin-Ciocalteu reagent.

Conclusion

This study shows that P. hyrcanicum contains phenolic compounds with in vitro activity that can be useful in the context of preventing or mitigating cellular damages linked to diabetic conditions.     

The α-glucosidase inhibitory activity of avicularin and 4-O-methyl gallic acid isolated from Syzygium myrtifolium leaves

Diabetes Mellitus is the main cause of death on a global scale. In 2019, there were 463 million people with diabetes, and WHO predicts that by 2030, there will be 578 million. As an antidiabetic agent, α-glucosidase inhibitors are one of the methods employed to reduce the prevalence of diabetes. Diabetes is traditionally treated with Syzygium as a primary material, medicine, fruit, ornamental plant, and source of carpentry. This investigation aimed to examine the inhibitory effect of seven species of Syzygium against α-glucosidase enzyme using an in vitro assay and isolate active substances and ascertain their concentrations in each sample. As a solvent, ethanol was used in maceration to extract the substance. Afterward, the extract underwent a series of fractionation techniques, including liquid–liquid extraction, vacuum liquid chromatography, column chromatography, and preparative Thin Layer Chromatography (TLC) for purification and isolation. The compound's structures were elucidated using TLC, UV–Visible spectrophotometry, and nuclear magnetic resonance (NMR) spectroscopy. Based on concentrations of 100 and 200 µg/mL, Syzygium myrtifolium exhibited the most significant inhibitory effect, followed by other species of Syzygium. The proportion of ethyl acetate had the strongest activity (IC₅₀ 0.40 ± 0.02 µg/mL) contrasted to positive control acarbose (IC₅₀ 55.39 ± 0.67 g/mL) and quercitrin (IC₅₀ 6.47 ± 0.40 µg/mL). Avicularin and 4-O-methyl gallic acid were discovered in the ethyl acetate fraction of Syzygium myrtifolium with IC₅₀ values of 17.05 ± 0.75 µg/mL and 25.19 ± 0.21 µg/mL, respectively. As α-glucosidase inhibitory, the results of this study indicate Syzygium myrtifolium can be used as a dietary supplement to manage hyperglycemia.     

Bioevaluation of synthetic pyridones as dual inhibitors of α-amylase and α-glucosidase enzymes and potential antioxidants

Herein, a library of novel pyridone derivatives 1–34 was designed, synthesized, and evaluated for α-amylase and α-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1–34 were synthesized via a one-pot multi-component reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1–34 were structurally characterized by different spectroscopic techniques. Most of the tested compounds showed more promising inhibition potential than the standard acarbose (IC₅₀ = 14.87 ± 0.16 µM) but compounds 13 and 12 were found to be the most potent compounds with IC₅₀ values of 9.20 ± 0.14 µM and 3.05 ± 0.18 µM against α-amylase and α-glucosidase enzymes, respectively. Compounds 1–34 also displayed moderate antioxidant potential in the range of IC₅₀ = 96.50 ± 0.45 to 189.98 ± 1.00 µM in comparison to the control butylated hydroxytoluene (BHT) (IC₅₀ = 66.50 ± 0.36 µM), in DPPH radical scavenging activities. Additionally, all synthetic derivatives were subjected to a molecular docking study to investigate the interaction details of compounds 1–34 (ligands) with the active site of enzymes (receptors). These results indicate that the newly synthesized pyridone class may serve as promising lead candidates for controlling diabetes mellitus and as antioxidants.     

Kinetics of α-glucosidase inhibition by different fractions of three species of Labiatae extracts: a new diabetes treatment model

Context: Glucosidases are a group of enzymes playing crucial roles in digestion of carbohydrates. Glucosidase inhibitors can reduce carbohydrate digestion rate and have the potential to prevent development of type 2 diabetes. The Labiatae is one of the largest plant families grown globally and many studies that have isolated new pharmaceutical compounds. In folk medicine, some of Labiatae plants such as Zataria multiflora Boiss, Salvia mirzayanii Rech. F. &; Esfand, and Otostegia persica Boiss are consumed for the treatment of diabetes.

Objectives: This study investigates the inhibitory effects of different fractions of three mentioned species extracts on α-glucosidase.

Materials and methods: Ethanol extracts of these plants leaves were fractionated using petroleum ether, chloroform, ethyl acetate, and n-butanol solutions. The duration of this study was 12?months. To measure enzyme inhibition, 5?μL of the enzyme, 20?μL of substrate and samples were used and for evaluation mode of inhibition, constant amounts of α-glucosidase were incubated with rising concentrations of substrate (PNPG).

Results: The results revealed that the ethyl acetate fraction of Zataria multiflora (IC₅₀ =?0.35?±?0.01?mg/mL) and petroleum ether fraction of Salvia mirzayanii (IC₅₀ =?0.4?±?0.11?mg/mL) were the most potent inhibitors of α-glucosidase in comparison with the other samples and acarbose as the standard (IC₅₀ =?7?±?0.19?mg/mL). All of the samples exhibited noncompetitive-uncompetitive inhibition.

Discussion and conclusion: It can be inferred from this study that α-glucosidase inhibitory potential of the studied extracts may be a marker of antidiabetic potential of these extracts.     

Antioxidant and α-glucosidase inhibitory compounds from Pimpinella candolleana Wight et Arn.

EtOAc and MeOH different extracts of Pimpinella candolleana Wight et Arn. have shown the α-glucosidase inhibitory and antioxidant activities when they were assayed in vitro. Chemical constituents of both extracts were isolated by column chromatography, and identified by MS and NMR spectroscopic data. Nine compounds were isolated, including 3 sterols, 2 flavones, 1 triterpene, 1 glucoside, 1 phenol derivatives, and 1 other compound. Their structures were identified as ursolic acid (1), luteolin (2), urea (3), stigmasta-5,22-dien-3-ol acetate (4), erythrol (5), isovitexin (6), 1-(4-hydroxyphenyl)-1,2-ethanediol (7), daucosterol (8), and β-sitosterol (9). Compound 1 (IC₅₀?=?4.42?μg?ml^?1), 2 (IC₅₀?=?5.96?μg?ml^?1), 4 (IC₅₀?=?67.43?μg?ml^?1) and 6 (IC₅₀?=?68.71?μg?ml^?1) showed α-glucosidase inhibitory activity. Compound 2 (IC₅₀?=?0.99?μg?ml^?1) had antioxidant activity. All compounds except for 1 and 9 were isolated from this genus for the first time.     

Evaluation of silver-doped indium oxide nanoparticles as in vitro α-amylase and α-glucosidase inhibitors

Pristine and 2 % silver-doped indium oxide (In₂O₃) nanoparticles, synthesized by solution combustion method, yielded spherical nanoparticles in the range of 20–30 nm. The nanoparticles were stabilized in cubic bixbyite structure as revealed from X-ray diffraction study. In order to evaluate the potential of these nanoparticles to modulate enzyme activity, α-amylase and α-glucosidase were used as model enzymes. Pristine and 2 % silver-doped In₂O₃ nanoparticles demonstrated dose-dependent inhibition of α-amylase and α-glucosidase activities. Pristine In₂O₃ nanoparticles demonstrated 26.4 % (300 µg/mL) and 65.3 % (300 µg/mL) inhibition against α-amylase and α-glucosidase, respectively. In contrast, silver-doped In₂O₃ nanoparticles depicted 94.1 % (300 µg/mL) and 99.6 % (0.18 µg/mL) inhibition against α-amylase and α-glucosidase, respectively. In comparison with acarbose, a standard anti-diabetic drug that depicted absolute inhibition of α-glucosidase activity at 300 µg/mL, 2 % silver-doped In₂O₃ nanoparticles completely inhibited α-glucosidase at a very low concentration (0.18 µg/mL). In view of our results, the activity of α-amylase and α-glucosidase, which are targets for treatment of type 2 diabetes, can be modulated using silver-doped In₂O₃ nanoparticles in the concentration-dependent manner. Therefore, silver-doped In₂O₃ has a potential to be used as a prospective starch blocker.     

Antidiabetic potential and enzyme kinetics of benzothiazole derivatives and their non-bonded interactions with α-glucosidase and α-amylase

Benzothiazole derivatives were synthesized and their antidiabetic potential evaluated using α-glucosidase, α-amylase, non-enzymatic glycosylation of hemoglobin and advanced glycation end product inhibition assays. Compound 3l showed low IC₅₀ values of 0.31, 0.98, 0.59 and 0.19 mM in α-amylase, α-glucosidase, non-enzymatic glycosylation of hemoglobin and AGE inhibition assays, respectively, and outperformed the standard acarbose. Enzyme kinetic studies revealed that it has a K _i of 0.39 and 1.5 mM for α-amylase and α-glucosidase, respectively. The non-bonded interactions of 3l with α-amylase (3OLD) and α-glucosidase (2ZE0) showed that it binds in the active site pocket and is surrounded by residues Asp197, Glu233, Asp300 in 3OLD and Asp199, Glu256, Asp326 in 2ZE0.