Management Of Postprandial Hyperglycemia Research Articles

Discovery of triazole tethered thymol/carvacrol-coumarin hybrids as new class of α-glucosidase inhibitors with potent in vivo antihyperglycemic activities

Keeping in view the inhibitory potential of monoterpenes thymol and carvacrol as well as coumarin nucleus against α-glucosidase, novel series of thymol/carvacrol-coumarin hybrids was designed, synthesized and evaluated for α-glucosidase inhibitory potential. Among the series of hybrid molecules, AS14 with IC50 value of 4.32 ± 0.11 μM was selective α-glucosidase inhibitor over α-amylase (IC50 = 37.36 ± 0.84 μM). AS14 was non-toxic toward mouse normal fibroblast cells (L929: IC50 > 100 μM). Molecular docking and dynamic simulation studies confirmed desired interactions of AS14 with α-glucosidase responsible for the inhibition of its catalysis capabilities. Acute oral toxicity study confirmed AS14 as safer molecule for in vivo pharmacological investigations with LD50 value of 300 mg/kg. AS14 also showed acute hypoglycaemic effects [reduction in blood glucose levels at 1 hr of administration in maltose loading test (at 10 and 20 mg/kg by 62.65 % and 70.12 %) and sucrose loading test (at 10 and 20 mg/kg by 59.65 % and 60.23 %), respectively] as well as long term (28 days) fasting blood glucose reduction (At day 28: 10 mg/kg = 54.69 % and 20 mg/kg = 62.23 % reduction in fasting blood glucose levels) capabilities in streptozotocin induced diabetic rats. Overall study represents, AS14 as potential α-glucosidase inhibitor with adequate efficacy and safety profile and act as an effective hit lead for the further development of potent and safer α-glucosidase inhibitors for the management of postprandial hyperglycemia in diabetic patients.

Curbing Key Digestive Enzymes by Three Plant Extracts for Sustainable Management of Postprandial Hyperglycemia

Background: Diabetes mellitus is a chronic metabolic condition marked by persistently elevated blood sugar levels. Key digestive enzymes viz. α-amylase and α-glucosidase, hydrolyze consumed carbohydrates into glucose which raises the postprandial blood glucose level in a diabetic patient. So, the development of α-amylase and α-glucosidase inhibitors procured from medicinal plants to retard starch digestion is an alternative approach for controlling type 2 diabetes mellitus. Objective: The current study aimed to evaluate the inhibitory potentials of the key digestive enzymes viz. α-amylase and α-glucosidase by the extracts of three medicinal plants; red dragon fruit (Hylocereus polyrhizus) pulp and peel, bamboo (Bambusa vulgaris) shoot, turnip (Brassica rapa L.) shoot and leaf by performing α-amylase and α-glucosidase inhibition assays in vitro. Methods: Inhibition of α-amylase activity was conducted using 3,5-dinitrosalicylic acid method, and 4-Nitrophenyl-α-D-glucopyranoside was used as a substrate to perform α-glucosidase inhibition assay in vitro. Results: Among all the selected sample extracts, red dragon fruit pulp expressed the highest percentage of α-amylase inhibition (59.73±4.33%) at the concentration of 1000 μg/mL which is comparable to standard antidiabetic drug Acarbose (70.59±2.64%), whereas the lowest inhibition was observed in turnip shoot extract (42.48±2.10%) at the same concentration. In terms of α-glucosidase inhibition activity, again, red dragon fruit pulp extract demonstrated the maximum inhibition rate (56.42±2.38%) at 1000 μg/mL concentration. This is respectable in comparison to the reference Acarbose (66.45±1.78%). In contrast, turnip shoot extracts displayed the lowest α-glucosidase inhibition activity (38.27±2.21%) at the same concentration. Conclusion: The current study demonstrated that the red dragon fruit pulp extract possesses substantial antihyperglycemic activity (α-amylase inhibition: 59.73±4.33%, α-glucosidase inhibition: 56.42±2.38%) in vitro, which could be a putative nutraceutical to manage postprandial hyperglycemia.

Restraint of Starch-hydrolyzing Enzyme in the Management of Postprandial Blood Glucose Level: An Alternative Approach

Background: Diabetes is a multifaceted metabolic condition defined by postprandial hyperglycemia with perturbances in the majority of the metabolic systems in the human body. α-amylase is a key enzyme present in pancreatic juice and saliva that converts one of the common food sources i.e., starch molecules into absorbable molecules and raises plasma glucose levels. Reducing starch digestion by the inhibitors of starch hydrolyzing enzymes could be an intriguing strategy for improved postprandial hyperglycemia management. Objective: The present research work was undertaken to evaluate the inhibition potential of natural inhibitors of α-amylase from Trichosanthes dioica (pointed gourd) and Moringa oleifera (moringa leaves) extracts in vitro. Furthermore, in vivo cytotoxicity assessment was also conducted through brine shrimp lethality bioassay. Methods: Different organic solvents (namely acetone, ethanol, and methanol) were used to isolate plant extracts. DNS (3,5-dinitrosalicylic acid) was used to conduct the α-amylase inhibition assay. The safety of the natural inhibitors was determined by the most common technique i.e, brine shrimp lethality bioassay. Results: Among all the different organic solvent extracts, pointed gourd and its peel exhibited the highest α-amylase inhibition activity (64.03±7.33–69.40±9.38%) which is very close to standard α-amylase inhibitor acarbose (72.34±4.23%) whereas moringa leaves showed moderate inhibition activities (59.10±5.25–62.03±1.77%). The cytotoxicity of pointed gourd and its peel was higher while moringa leaves demonstrated lower toxicity. Conclusion: Considering the inhibition rate and cytotoxicity, pointed gourd ethanol extract (Inhibition: 67.43±11.80%; Cytotoxicity: 209.98 μg/mL) would be the best candidate for managing postprandial hyperglycemia.

Parsing structural fragments of thiazolidin-4-one based α-amylase inhibitors: A combined approach employing in vitro colorimetric screening and GA-MLR based QSAR modelling supported by molecular docking, molecular dynamics simulation and ADMET studies

α-Amylase (EC.3.2.1.1) is a ubiquitous digestive endoamylase. The abrupt rise in blood glucose levels due to the hydrolysis of carbohydrates by α-amylase at a faster rate is one of the main reasons for type 2 diabetes. The inhibitors prevent the action of digestive enzymes, slowing the digestion of carbs and eventually assisting in the management of postprandial hyperglycemia. In the course of developing α-amylase inhibitors, we have screened 2-aryliminothiazolidin-4-one based analogs for their in vitro α-amylase inhibitory potential and employed various in silico approaches for the detailed exploration of the bioactivity. The DNSA bioassay revealed that compounds 5c, 5e, 5h, 5j, 5m, 5o and 5t were more potent than the reference drug (IC60 value = 22.94 ± 0.24 μg mL−1). The derivative 5o with –NO2 group at both the rings was the most potent analog with an IC60 value of 19.67 ± 0.20 μg mL−1 whereas derivative 5a with unsubstituted aromatic rings showed poor inhibitory potential with an IC60 value of 33.40 ± 0.15 μg mL−1. The reliable QSAR models were developed using the QSARINS software. The high value of R2ext = 0.9632 for model IM-9 showed that the built model can be applied to predict the α-amylase inhibitory activity of the untested molecules. A consensus modelling approach was also employed to test the reliability and robustness of the developed QSAR models. Molecular docking and molecular dynamics were employed to validate the bioassay results by studying the conformational changes and interaction mechanisms. A step further, these compounds also exhibited good ADMET characteristics and bioavailability when tested for in silico pharmacokinetics prediction parameters.

Inhibition Kinetics and Theoretical Studies on Zanthoxylum chalybeum Engl. Dual Inhibitors of α-Glucosidase and α-Amylase.

Compounds from Zanthoxylum chalybeum Engl. were previously reported for inhibitory activities of amylase and glucosidase enzymatic action on starch as a preliminary study toward the establishment of a management strategy against postprandial hyperglycemia, however, the inhibitory kinetics and molecular interaction of these compounds were never established. A study was thus designed to establish the inhibitory kinetics and in silico molecular interaction of α-glucosidase and α-amylase with Z. chalybeum metabolites based on Lineweaver-Burk/Dixon plot analyses and using Molecular Operating Environment (MOE) software, respectively. Skimmianine (5), Norchelerythrine (6), 6-Acetonyldihydrochelerythrine (7), and 6-Hydroxy-N-methyldecarine (8) alkaloids showed mixed inhibition against both α-glucosidase and α-amylase with comparable Ki to the reference acarbose (p > 0.05) on amylase but significantly higher activity than acarbose on α-glucosidase. One phenolic 2,3-Epoxy-6,7-methylenedioxyconiferol (10) showed a competitive mode of inhibition both on amylase and glucosidase which were comparable (p > 0.05) to the activity of acarbose. The other compounds analyzed and displayed varied modes of inhibition between noncompetitive and uncompetitive with moderate inhibition constants included chaylbemide A (1), chalybeate B (2) and chalybemide C (3), fagaramide (4), ailanthoidol (9), and sesame (11). The important residues of the proteins α-glucosidase and α-amylase were found to have exceptional binding affinities and significant interactions through molecular docking studies. The binding affinities were observed in the range of -9.4 to -13.8 and -8.0 to -12.6 relative to the acarbose affinities at -17.6 and -20.5 kcal/mol on α-amylase and α-glucosidase residue, respectively. H-bonding, π-H, and ionic interactions were noted on variable amino acid residues on both enzymes. The study thus provides the basic information validating the application of extracts of Z. chalybeum in the management of postprandial hyperglycemia. Additionally, the molecular binding mechanism discovered in this study could be useful for optimizing and designing new molecular analogs as pharmacological agents against diabetes.

Inhibitory effect of gallic acid from Thunbergia mysorensis against α-glucosidase, α-amylase, aldose reductase and their interaction: Inhibition kinetics and molecular simulations

In this exploration, we assessed the antihyperglycaemic properties of methanol extract of flowers of Thunbergia mysorensis (MeT) against α-glucosidase, α-amylase and aldose reductase enzymes for the effective management of postprandial hyperglycemia. Hyperglycemia occurs when the body lacks enough insulin or is unable to correctly utilize it. MeT inhibited both the carbohydrate digestive enzymes (α-glucosidase and α-amylase) and aldose reductase, which are vital for the therapeutic control of postprandial hyperglycaemia. MeT was also found to have significant antioxidant activity. Using several spectroscopic approaches, the primary active component found in MeT was identified as gallic acid. With low Ki values, gallic acid significantly inhibited α-glucosidase (30.86 µg/mL) and α-amylase (6.50 µg/mL). Also, MeT and gallic acid both inhibited aldose reductase effectively, corresponding to an IC50 value of 3.31 and 3.05 µg/mL. Our findings imply that the presence of polyphenol compounds (identified via HPLC analysis) is more likely to be responsible for the antihyperglycaemic role exhibited by MeT via the inhibition of α-glucosidase and the polyol pathway. Further, gallic acid interacted with the key residues of the active sites of α-glucosidase (−6.4 kcal/mol), α-amylase (−5.8 kcal/mol) and aldose reductase (−5.8 kcal/mol) as observed in the protein-ligand docking. It was also predicted that gallic acid was stable inside the binding pockets of the target enzymes during molecular dynamics simulation. Overall, gallic acid derived from MeT via bioassay-guided isolation emerges as a natural antidiabetic drug and can be taken into in vivo and clinical studies shortly. Communicated by Ramaswamy H. Sarma

Characterization of α-Glucosidase Inhibitor <i>Streptomyces</i> sp. IPBCC.a.29.1556 Aqueous Extract: An Endophyte of Indonesian <i>Ficus deltoidea</i>

Filamentous bacteria have been known as actinobacteria which could produce various secondary metabolites, including an α-glucosidase inhibitor. The α-glucosidase inhibitor has been identified to be potentially valuable for the treatment of diabetes mellitus. Endophytic actinobacteria are able to produce bioactive compounds that are similar to their hosts. Indonesian Ficus deltoidea is one of the medicinal plants which has the activity of the α-glucosidase inhibitor. The α-glucosidase inhibitor has been characterized by optimizing compound production, fractionation, analysis using TLC and LC-MS, and identifying inhibitor mechanisms. The α-glucosidase inhibitor substance is present in Streptomyces sp. IPBCC.a.29.1556 aqueous extract. The aqueous extract was separated and fraction 1 had an IC50 value of 58.8 μg/mL, which is better than acarbose (IC50 = 90.4 μg/mL). Kinetic studies revealed that this fraction inhibited the enzyme through a non-competitive mechanism. Chemical profile based on LC-MS, fraction 1 showed the presence of Phenylpropynal, Butyric acid, 2-(2-Ethoxyethoxy)ethanolate, 1,1-Diethoxyethane acetate, N,N-dimethyl-3-oxide-1H-Benzotriazole-1-propanamine, p-coumaric acid, and isoquinolinium which might contribute individually or synergistically to the observed α-glucosidase inhibitor activity. These results suggest that fraction 1 from the aqueous extract of Streptomyces sp. IPBCC.a.29.1556 is the potential source to produce an α-glucosidase inhibitor for the management of postprandial hyperglycemia.

Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches.

Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential of coumarin derivatives and coumarin-based scaffolds against α-glucosidase and α-amylase for the management of postprandial hyperglycemia. Hyperglycemia is a condition where an excessive amount of glucose circulates in the bloodstream. It occurs when the body lacks enough insulin or is unable to correctly utilize it. With open-source and free in silico tools, we have investigated novel 80 coumarin derivatives for their inhibitory potential against α-glucosidase and α-amylase and identified a coumarin derivative, CD-59, as a potential dual inhibitor. The ligand-based 3D pharmacophore detection and search is utilized to discover diverse coumarin-like compounds and new chemical scaffolds for the dual inhibition of α-glucosidase and α-amylase. In this regard, four novel coumarin-like compounds from the ZINC database have been discovered as the potential dual inhibitors of α-glucosidase and α-amylase (ZINC02789441 and ZINC40949448 with scaffold thiophenyl chromene carboxamide, ZINC13496808 with triazino indol thio phenylacetamide, and ZINC09781623 with chromenyl thiazole). To summarize, we propose that a coumarin derivative, CD-59, and ZINC02789441 from the ZINC database will serve as potential lead molecules with dual inhibition activity against α-glucosidase and α-amylase, thereby discovering new drugs for the effective management of postprandial hyperglycemia. From the reported scaffold, the synthesis of several novel compounds can also be performed, which can be used for drug discovery.

Unravelling the comparative metabolite fingerprints and therapeutic effects of diverse teas

The comparative metabolite fingerprinting and bioactivity of different teas viz. green tea, oolong tea, white tea, orthodox black tea, and Cut/crush, Tear and Curl (CTC) black tea as compared to unprocessed tea leaves (GTL) were elucidated. The fresh tender tea shoots collected from single location were processed into different tea forms and brewed homogenously. The mass fingerprinting analysis using ultra high performance liquid chromatography ion mobility quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-IMS) revealed substantial variability of key metabolites among different tea brews. Statistical analysis (Venn-diagram, Heatmap and PCA) has revealed significant variation in metabolites content among different teas. Catechins and caffeine were identified and quantified in all infusions using high-pressure liquid chromatography analysis. 2,2-diphenyl-1- picrylhydrazyl (DPPH) free radical scavenging assay, 2,2′-azino-bis (3 ethylbenzothiazoline-6-sulphonic acid (ABTS) radical cation decolourisation assay and ferric-reducing antioxidant power (FRAP) assay unveiled significant antioxidant potential by all the infusions. The results of α-glucosidase inhibition by different teas showed positive effects in management of postprandial hyperglycemia. The tea samples also unveiled significant results for nitric oxide inhibition in lipopolysaccharide-stimulated RAW 264.7 macrophages and cytotoxicity against A-549 and CT26.CL25 cancer cells. Hence, it has established that tea processing has substantial role on key metabolite composition and therapeutic potential of different tea infusions.

Antidiabetic Potential and Chemical Constituents of Haloxylon scoparium Aerial Part, An Endemic Plant from Southeastern Algeria

Diabetes mellitus is a chronic metabolic disease. Traditional medicines are currently still popular as an alternative in the treatment of this disease. However, the mechanism of action in lowering blood sugar of most folk recipes remains unproven. The objective of this study is to evaluate the antidiabetic potential of an Algerian halophyte in regulating postprandial hyperglycemia via α-amylase inhibitory activity. For this, methanolic and aqueous crude extracts were prepared from the aerial part of Haloxylon scoparium Pomel and analyzed by HPLC/ UV method. Total flavonoids, total tannins and total alkaloids as specific extracts were also prepared from the same part. The in vitro α-amylase inhibition assay using starch-iodine was performed. As results, the methanolic crude extract seems to be the best with 29 phenolic compounds of which the most abundant is gallic acid. All tested extracts showed better α-amylase inhibitory activities. Among these extracts and compared to acarbose (IC50 = 17.96 µg/ mL), the methanolic crude extract had the highest inhibitory activity (IC50 = 22.9 µg/ mL), followed by total flavonoids and alkaloids. Finally, we conclude that Haloxylon scoparium aerial part had displayed maximum inhibition against α-amylase enzyme especially with its methanolic crude extract. It can be used for management of postprandial hyperglycemia with lesser side effects and provide a strong rationale for further animal and clinical studies.

Magnetically anchored antibody-coupled nanocomposite as α-Amylase inhibitor for long-time protection against glycemic variability

Glycemic variability is an important risk factor for metabolic diseases such as diabetes, obesity and cardiovascular diseases, which are closely related to life and diet style. Random eating or eating irregular meals and poor patient compliance with lifestyle changes often happens and makes more difficult to control glycemic variability in life through hypoglycemic drugs around meals. The inhibition of the activity of digestion enzymes in the gut represents an effective strategy for prevention and treatment of glycemic variability. In this study, immune response was employed to induce antibodies (immunoglobulin of egg yolk, IgY) against α-amylase through the subcutaneous injection of α-amylase as the antigen in laying hens. IgY-coupled magnetic nanocomposite hydrogel as α-amylase inhibitor was further developed for long-time against glycemic variability. IgY was covalently coupled to PEG-coated Fe3O4 nanoparticles (PEG/Fe3O4@IgY nanoparticles) and then fabricated by embedding of PEG/Fe3O4@IgY nanoparticles in chitosan-alginate (CS/AS) hydrogels. Under the external magnetic field, lgY-coupled magnetic nanocomposites as α-amylase inhibitors were magnetically anchored in the small intestine for long-time against glycemic variability, resulting in a long-time (>36 h) and effective postprandial hyperglycemia management. This study opens a new door to the health care of the metabolic diseases such as diabetes, obesity and cardiovascular disease.

Analysis of Chemical Composition by GC-MS and In-vitro Antidiabetic Activity of Azadirachta Indica Leaves Collected from Erbil, Iraq

Background: Azadirachta indica (Neem) is an important medicinal plant that is traditionally known for its insecticidal, and antimicrobial properties. Objective: The objective of present study was to evaluate the in-vitro antidiabetic activity and characterize the chemical constituents of Neem extract. Materials and Methods: The chemical constituents in ethyl acetate extract of the Neem leaves was determined by GC-MS and the in-vitro antidiabetic activity of Neem extract was evaluated via inhibition of α-amylase and α-glucosidase enzymes. Results: The ethyl acetate extract of Neem yielded 49 chemical compounds and these constituents amounting to 97.07% of total Neem leaf extract composition. The major chemical components of the Neem were octadecanoic acid (7.17%), propyl tetracosyl ether (5.35%), 1-decanol, 2-octyl (5.01%), hexadecane (4.70%), tricosane (4.73%), octadecane, 1-chloro (4.65%), and linolenic acid (4.35%). The Neem extract produces dose dependent-inhibition of α-amylase and α-glucosidase enzymes ranging from 21.67±2.81 to 75.82±3.44% and 17.04±4.43 to 58.44±1.21% for concentration 31.25 to 1000 µg/mL, respectively. The IC50 values for Neem extract and acarbose were 165.53±2.75 and 91.04±2.16 µg/mL, respectively against the α-amylase enzyme. The IC50 values for Neem extract and acarbose were 210.08±2.16 and 120.05±2.16 µg/mL, respectively against the α-glucosidase enzyme. Conclusion: The study findings suggested that Neem may be used as drug candidate in the management of post prandial hyperglycemia.

The effects of short term hyperglycemia on human red blood cells studied using Raman spectroscopy and optical trap.

Management of postprandial hyperglycemia is important for preventing severe complications like cardiovascular disease in diabetes patients. The associated glycemic instability in postprandial hyperglycemia may also cause disorders in circulating red blood cells (RBCs). Therefore, effects of short-term hyperglycemic stress on RBCs such as occur in the postprandial condition, have been studied here ex vivo using single-cell Raman spectroscopy and optical trapping. RBCs incubated in high glucose containing media relevant to postprandial hyperglycemia were studied for changes with respect to controls by analyzing the single-cell Raman spectra acquired with Raman optical tweezers with 532nm excitation light. Use of 532nm light for exciting Raman spectra also results in simultaneous photoreduction of intracellular hemoglobin (Hb). The level of photoreduction was noticed to be limited in hyperglycemia-exposed cells in comparison to the control. Since this suggests formation of permanently oxidized Hb in hyperglycemia-exposed RBCs, a fluorescence study was performed which showed elevated levels of oxidative stress in these cells. The changes in the RBC membrane, which may result due to higher levels of oxidative stress, were investigated using optical stretching experiments under the laser trap. The results indicated a loss of elasticity for the RBC membrane due to hyperglycemic exposure.

Chemical Characterization and α-Glucosidase Inhibitory Activity of Essential Oil of Lavandula angustifolia Flowers

Lavandula angustifolia is a major source of high-quality fragrance and extensively used in aromatherapy. Lavender is widely found in the Jammu and Kashmir region of India. The aim of the present study to determine chemical constituents present in the essential oil of L. angustifolia flowers by gas chromatography-mass spectrometry and to evaluate its antihyperglycemic activity via inhibition of the α-glucosidase enzyme. The chemical constituents of the essential of L. angustifolia flowers were determined by gas chromatography-mass spectrometry and its antihyperglycemic activity was evaluated by inhibition of the α-glucosidase enzyme. The Lavender flowers yielded 41 chemical constituents which constitute about 99.28 % of total essential oil and the major chemical constituents include linalyl acetate (39.28 %), linalool (26.76 %), trans-β-caryophyllene (4.77 %), lavandulyl acetate (3.04 %) and 1,8-cineole (2.15 %). The essential oil from flowers of L. angustifolia showed concentration dependant α-glucosidase enzyme inhibition that varies from 24.27±2.18 to 64.04±1.29 % for concentration 31.25 to 1000 μg/mL, respectively. The L. angustifolia essential oil with IC50 value 609.44±13.01 was found comparable with acarbose (IC50 value 526.5±12.19 μg/mL) against the α-glucosidase enzyme. The study finding provides the basis for the possible use of L. angustifolia essential oil in the management of postprandial hyperglycemia in diabetic patients.

Characterization of an Endemic Plant Origanum grosii from Morocco: Trace Element Concentration and Antihyperglycemic Activities

Origanum genus is one of the most widely used herbs in folk medicine for its biological properties. The present investigation aims to characterize, for the first time, endemic Origanum grosii collected from the Taounate region, Morocco. This characterization was realized by determining the concentration of metals in different parts of the plant (flowers, leaves, and stems) by ICP-MS, and the results were studied statistically by Principal Component Analysis (PCA). Phytochemical screening with the dosage of polyphenols and flavonoids has been conducted. To know more about this species, antihyperglycemic tests have been performed to highlight the presence or absence of the antidiabetic effect for this plant. An Oral Glucose Tolerance Test (OGTT) has been performed on normal mice which were divided into two groups of six mice each. Group 1 (control group) was treated with distilled water, and group 2 was treated with an aqueous extract of O. grosii by gavage at 150 mg/kg. Digestive enzyme α-amylase inhibition assay has also been evaluated to study the inhibition effect of the studied extract using acarbose as a control. The results showed that the leaves exhibited a high concentration of trace elements (Ca, Mg, and K) and total absence of heavy metals, which were found in small quantities (Cr, Ni, and B) on the stems, and this makes the plant safe to use. On the other hand, tannins, flavonoids, triterpenes, and steroids were the major families strongly present in this species. The antidiabetic results showed that O. grosii have significantly reduced postprandial hyperglycemia after glucose loading in normal rats. It showed also that this species has a significant antihyperglycemic activity reflected by the inhibition of α-amylase. The one responsible for this property could be the synergy between the trace elements and the nature of the chemical families of O. grosii species, which can make this plant useful in the management of postprandial hyperglycemia.

Improvement in serum amylase and glucose levels in diabetic rats on oral administration of bisdemethoxycurcumin from Curcuma longa and limonoids from Azadirachta indica.

Curcuma longa and Azadirachta indica are traditionally used in Indian cuisine and Ayurvedic medicine as nutraceuticals against diabetes. The crude C.longa isopropanol extract, bisdemethoxycurcumin (BDMC), the purified bioactive component from C.longa, and limonoids azadiradione, gedunin from A.indica, are able to inhibit in vitro the antidiabetic target human pancreatic α-amylase independently. However, no reports on their in vivo efficacy in animal models exist. Thus, the antidiabetic effect of these orally administered human pancreatic α-amylase inhibitors was performed on streptozotocin-induced Sprague-Dawley rats. Initially, the normal rats were treated with test compounds (10-100mg/kg of body weight) in corn oil (5ml/kg), and as no lethality was observed in these doses, further studies were carried out with lowest concentration of 10mg/kg of body weight. A reduction in area under curve (AUC) suggested glucose-lowering effect of these compounds in starch fed diabetic rats. The efficacy study showed a significant improvement in body weight, blood glucose levels, serum amylase, and fructosamine levels as well in other serum parameters associated with diabetes with respect to liver and renal functions. Hence, under in vivo conditions, inhibition of α-amylase activity by BDMC and limonoids affirms it as one of the mechanisms of action resulting in reduction of blood glucose levels. PRACTICAL APPLICATIONS: Bisdemethoxycurcumin from C.longa and limonoids, namely, azadiradione and gedunin, from A.indica are potent inhibitors of the antidiabetic target human pancreatic α-amylase. Oral Starch Tolerance Test (OSTT) and 28-day efficacy study to check the effect of these orally administered inhibitors in diabetic rat models showed significant improvements in serum blood glucose and amylase levels as well as in other diabetes related serum parameters, namely, bilirubin, lipids, lactate dehydrogenase, alkaline phosphatase, and urea. The study contributes to understanding the action and efficacy of these pancreatic α-amylase inhibitors and suggests a potential role for them as nutraceuticals/therapeutics in management of post-prandial hyperglycemia.

Effects of ultrasound-assisted extraction (UAE), high voltage electric field (HVEF), high pressure processing (HPP), and combined methods (HVEF+UAE and HPP+UAE) on Gac leaves extraction

Emerging processing technologies and their combinations might be promising approaches to overcome the limitations of the conventional extraction method (CEM). In this study, ultrasonic-assisted extraction (UAE, 150 W, 20 min), high voltage electric field (HVEF, 4000 kV m−1 min), and high-pressure processing (HPP, 300 MPa, 3 min) were used in comparison with the CEM to extract Gac leaves (Momordica cochinchinensis Spreng). Besides, two innovative combined methods, i.e., HVU (HVEF+UAE) and HPU (HPP+UAE), were proposed and investigated. Total phenolic content (TPC), total flavonoid content (TFC), total chlorophyll content (TCC), SOD-like capacity, and carbohydrate-hydrolyzing enzyme inhibition of the extracts were measured. Also, polyphenolic compounds were identified by HPLC and the most contributors in the dataset were assessed by principal component analysis (PCA). Gac leaves extract was found to be a source of valuable bioactive compounds with antioxidant activity and hypoglycemic effects that can help with postprandial hyperglycemia management. Vanillic acid and myricetin had the most contributions to α-glucosidase and α-amylase inhibition ability. Combined emerging technologies (HVU and HPU) were superior to other methods due to the highest values of TPC (5200 mg GAE/100 g DW), TFC (620 mg QE/100 g DW), SOD-like activity (12,100 U/g DW), and inhibitory effects of α-glucosidase (38%, IC50 value of 20.5 mg/mL) and α-amylase (42%, IC50 value of 16.5 mg/mL).

Natural edible materials made of protein-functionalized aerogel particles for postprandial hyperglycemia management

α-Amylase inhibitors (α-AIs) delay digestion of dietary starch by inhibiting α-amylase in the gut, thereby reducing the postprandial glycemia, which is beneficial to the patients with obesity and diabetes. The proteinaceous α-AIs from wheat can effectively control starch digestion and regulate postprandial hyperglycemia. However, their gastric intolerance remains a challenge, which limits its commercial production and industrial application. In this study, sodium alginate/chitosan aerogels loaded with wheat protein α-AIs were prepared and evaluated as potential transportation and protection matrices for important components in food or pharmaceutical applications. Specifically, the biodegradable aerogel cross-linked with sodium alginate-chitosan-calcium chloride, has a large surface area and open porous structure, which can adsorb staple wheat proteins as an integrated edible material to block around 88,660 U/g of α-amylase activity. The aerogel particles were able to protect the activity of wheat α-AIs in the stomach, leading to the slow passage of the wheat α-AIs through the small intestine to inhibit starch digestion more effectively. Animal experiments further showed that the postprandial blood glucose levels in rats were effectively controlled through delayed increase, after administration of wheat protein-functionalized aerogel particles loaded with wheat α-AIs, which are natural biological macromolecules. This is a novel, safe, and economical method for the prevention and pretreatment of diabetes.

Exploring the binding interactions of structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase: Spectroscopic approach coupled with molecular docking

Postprandial hyperglycemia has orchestrated untimely death among diabetic patients over the decades and regulation of α-amylase activity is now becoming a promising management option for type 2 diabetes. The present study investigated the binding interactions of three structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase to ascertain the affinity of the ligands for α-amylase using spectroscopic and molecular docking methods. The ligands were characterized using 1H and 31P NMR spectroscopy and CHN analysis. Diselenoimidodiphosphinate ligand (DY300), dithioimidodiphosphinate ligand (DY301), and thioselenoimidodiphosphinate ligand (DY302) quenched the intrinsic fluorescence intensity of α-amylase via a static quenching mechanism with bimolecular quenching constant (Kq) values in the order of x1011 M-1s-1, indicating formation of enzyme-ligand complexes. A binding stoichiometry of n≈1 was observed for α-amylase, with high binding constants (Ka). α-Amylase inhibition was as follow: Acarbose > DY301>DY300>DY302. Values of thermodynamic parameters obtained at temperatures investigated (298, 304 and 310 K) revealed spontaneous complex formation (ΔG<0) between the ligands and α-amylase; the main driving forces were hydrophobic interactions (with DY300, DY301, except DY302). UV–visible spectroscopy and Förster resonance energy transfer (FRET) affirmed change in enzyme conformation and binding occurrence. Molecular docking revealed ligands interaction with α-amylase via some key catalytic site amino acid residues (Asp197, Glu233 and Asp300). DY301 perhaps showed highest α-amylase inhibition (IC50, 268.11 ± 0.74 μM) due to its moderately high affinity and composition of two sulphide bonds unlike the others. This study might provide theoretical basis for development of novel α-amylase inhibitors from dichalcogenoimidodiphosphinate ligands for management of postprandial hyperglycemia.

The Clinical Application of Mealtime Whey Protein for the Treatment of Postprandial Hyperglycaemia for People With Type 2 Diabetes: A Long Whey to Go.

Mitigating postprandial hyperglycaemic excursions may be effective in not only enhancing glycaemic control for people with type 2 diabetes but also reducing the onset of diabetes-related complications. However, there are growing concerns over the long-term efficacy of anti-hyperglycaemic pharmacotherapies, which coupled with their rising financial costs, underlines the need for further non-pharmaceutical treatments to regulate postprandial glycaemic excursions. One promising strategy that acutely improves postprandial glycaemia for people with type 2 diabetes is through the provision of mealtime whey protein, owing to the slowing of gastric emptying and increased secretion of insulin and the incretin peptides. The magnitude of this effect appears greater when whey protein is consumed before, rather than with, a meal. Herein, this dietary tool may offer a simple and inexpensive strategy in the management of postprandial hyperglycaemia for people with type 2 diabetes. However, there are insufficient long-term studies that have investigated the use of mealtime whey protein as a treatment option for individuals with type 2 diabetes. The methodological approaches applied in acute studies and outcomes reported may also not portray what is achievable long-term in practice. Therefore, studies are needed to refine the application of this mealtime strategy to maximize its clinical potential to treat hyperglycaemia and to apply these long-term to address key components of successful diabetes care. This review discusses evidence surrounding the provision of mealtime whey protein to treat postprandial hyperglycaemia in individuals with type 2 diabetes and highlights areas to help facilitate its clinical application.