Carbohydrate Digestive Enzymes Research Articles

Alkaloid extract of Lannea egregia leaf inhibits carbohydrate digestive enzymes and modulates gluconeogenic and nucleotide-hydrolyzing enzyme activities in oxidative isolated psoas muscles injury

Alkaloid extract of Lannea egregia leaf inhibits carbohydrate digestive enzymes and modulates gluconeogenic and nucleotide-hydrolyzing enzyme activities in oxidative isolated psoas muscles injury

GCMS fingerprints and phenolic extracts of Allium sativum inhibit key enzymes associated with type 2 diabetes

ObjectivesInhibition of carbohydrate digestion enzymes (α-amylase and α-glucosidase) has been reported in studies as a therapeutic approach for the management or treatment of type 2 diabetes mellitus, owing to its potential to decrease postprandial hyperglycemia. The anti-diabetic potential of Allium sativum (also known as garlic) against diabetes mellitus has been established. Therefore, in this study, we assessed the antidiabetic potential of A. sativum using in vitro enzyme assays after which we explored computational modelling approach using the quantified GC-MS identities to unravel the key bioactive compounds responsible for the anti-diabetic potential. MethodsWe used in vitro enzyme inhibition assays (α-amylase and α-glucosidase) to evaluate antidiabetic potential and subsequently performed gas chromatography–mass spectroscopy (GC-MS) to identify and quantify the bioactive compounds of the plant extract. The identified bioactive compounds were subjected to in silico docking and pharmacokinetic assessment. ResultsA. sativum phenolic extract showed high dose-dependent inhibition of α-amylase and α-glucosidase (p < 0.05). Interestingly, the extract inhibited α-glucosidase with a half maximal inhibitory concentration of 53.75 μg/mL, a value higher than that obtained for the standard acarbose. Docking simulation revealed that morellinol and phentolamine were the best binders of α-glucosidase, with mean affinity values of −7.3 and −7.1 kcal/mol, respectively. These compounds had good affinity toward active site residues of the enzyme, and excellent drug-like and pharmacokinetic properties supporting clinical applications. ConclusionsOur research reveals the potential of A. sativum as a functional food for the management of type 2 diabetes, and suggests that morellinol and phentolamine may be the most active compounds responsible for this anti-diabetic prowess. Therefore these compounds require further clinical asessment to demonstrate their potential for drug development.

Measuring key human carbohydrate digestive enzyme activities using high-performance anion-exchange chromatography with pulsed amperometric detection.

Carbohydrate digestion in the mammalian gastrointestinal tract is catalyzed by α-amylases and α-glucosidases to produce monosaccharides for absorption. Inhibition of these enzymes is the major activity of the drugs acarbose and miglitol, which are used to manage diabetes. Furthermore, delaying carbohydrate digestion via inhibition of α-amylases and α-glucosidases is an effective strategy to blunt blood glucose spikes, a major risk factor for developing metabolic diseases. Here, we present an in vitro protocol developed to accurately and specifically assess the activity of α-amylases and α-glucosidases, including sucrase, maltase and isomaltase. The assay is especially suitable for measuring inhibition by compounds, drugs and extracts, with minimal interference from impurities or endogenous components, because the substrates and digestive products in the enzyme activity assays are quantified directly by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD). Multiple enzyme sources can be used, but here we present the protocol using commercially available human α-amylase to assess starch hydrolysis with maltoheptaose as the substrate, and with brush border sucrase-isomaltase (with maltase, sucrase and isomaltase activities) derived from differentiated human intestinal Caco-2(/TC7) cells to assess hydrolysis of disaccharides. The wet-lab assay takes ~2-5 h depending on the number of samples, and the HPAE-PAD analysis takes 35 min per sample. A full dataset therefore takes 1-3 d and allows detection of subtle changes in enzyme activity with high sensitivity and reliability.

Antioxidant Activity and Inhibition of Carbohydrate Digestive Enzymes Activities of Artemisia campestris L.

Carbohydrate digestive enzymes play a major role in the management of the postprandial hyperglycemia. A chronic hyperglycemia can lead to serious health problems due to excessive production of several reactive oxygen species. Therefore, the inhibition of carbohydrate digestive enzyme and the use of antioxidant natural product can be an important strategy to control the glycaemia level and prevent against the complication of diabetes. The study aims to perform a phytochemical analysis, antioxidant activity, inhibitory effect on α -amylase, α -glucosidase (in vitro and in vivo) and the intestinal glucose absorption in Wistar rats of Artemisia campestris aqueous extract (AcAE) and hydro-ethanolic extract (AcEE). The test of total phenolic content, show that the AcAE has the highest quantity of polyphenol (44.65 ± 0.54 μ g GAE/mg extract) compared to the AcEE (31.7 ± 0.53 μ g GAE/mg extract) significantly. The amount of flavonoid and condensed tannins content in AcAE is 24.41 ± 3.57 μ g QrE/mg extract, 14.31 ± 5.26 μ g CE/mg respectively. The AcAE has also exhibit a great antioxidant activity in DPPH-scavenging and Ferric reducing antioxidant power assay (FRAP) compared to AcEE with an IC 50 = 0.355 ± 0.057 mg/mL and IC 50 = 0.269 ± 0.025 mg/mL. However, in a β -carotene bleaching assay the AcEE has the highest effect with an IC 50 = 0.319 ± 0.097 mg/mL. The both extract of Artemisia campestris L. (250 mg/kg) decreased postprandial hyperglycemia in the normal and alloxane diabetic rats in a very significant manner after starch or sucrose administration as an α -amylase and α -glucosidase substrate respectively. This result is confirmed in vitro by a remarkable inhibitory effect on α -amylase digestive enzymes by an IC 50 = 1.259 ± 0.128 mg/mL and IC 50 = 0.602 ± 0.072 mg/mL receptively for AcAE and AcEE. For the α -glucosidase enzyme, the both extracts significantly inhibit α -glucosidase activity compared to the control and they are almost similar to each other. Using a jejunum perfusion technique (in situ), Artemisia campestris L. decrease the intestinal D-glucose absorption activity significantly compared to the control and comparable to the Phlorizin used as a positive control by an amount of glucose absorbed equal a 6.53 ± 0.57, 5.34 ± 0.64 and 4.71 ± 0.24 mg/10 cm/h, for AcAE, AcEE and Phlorizin respectively. These results showed that the Artemisia campestris L. has highest phenolic content, antioxidant activity and demonstrated a postprandial anti-hyperglycemic effect via the inhibiting of the carbohydrate digestive enzyme ( α -amylase and α -glucosidase) and the intestinal glucose absorption.

Ameliorative effect of bayberry leaves proanthocyanidins on high sugar diet induced Drosophila melanogaster.

Bayberry leaves proanthocyanidins (BLPs) were distributed in natural plant food, considered to have the potential for metabolic syndrome. In this study, we raised Drosophila melanogaster on high sugar diet (HSD) from the egg stage to induce hyperglycemia, and the ameliorative effect of BLPs was assessed based on this model. Phenotypical, biochemical, and molecular analyses related to diabetes mellitus pathogenesis were measured. Flies exposed to BLPs were found to suppress the HSD-induced high glucose and high triglycerides levels. Moreover, BLPs showed an inhibitory effect on carbohydrate digestive enzymes (α-amylase and α-glucosidase) activity and mRNA expression, exhibiting the potential for carbohydrate digestion retardation. Transcriptional levels of key genes associated with glycolipid metabolism were further evaluated, including dilp, InR, and downstream dAKT-dFOXO-PEPCK, together with E78, SREBP, FAS, and LSD genes, were all downregulated after BLPs-exposure, suggesting the ameliorative effect of BLPs on dysbiosis associated with the insulin signaling pathway. This study provided a new functional compound, which is beneficial to further antidiabetic therapy studies.

Evaluation of anthoxanthins and their actions on digestive enzyme inhibition when used independently and in combination

Carbohydrate digestibility is a key determinant for elevated postprandial hyperglycemia (PPHG). Apart from dietary restrictions, one of the strategies to reduce PPHG is to limit the activity of carbohydrate digestive enzymes within the gastrointestinal tract in order to reduce monosaccharide absorption rates. The present work aimed to assess the inhibitory capabilities of digestive enzymes (e.g., α-glucosidase and α-amylase) by anthoxanthins when used independently, in combination with acarbose, or with a different anthoxanthin. Our results showed that quercetin, myricetin, and luteolin presented lower IC50 values than acarbose and inhibited α-glucosidase through mixed-type inhibition. On the other hand, acarbose when compared with these anthoxanthins, remained the most potent inhibitor of α-amylase. Combinatorial treatment (i) acarbose-quercetin and (ii) myricetin-luteolin showed synergistic activity (CI value less than 0.9) in α-glucosidase inhibition. An additive effect (CI value between 0.9 and 1.1) in α-glucosidase inhibition was observed when acarbose-myricetin, acarbose-luteolin or when a combination of two different anthoxanthins (quercetin-myricetin and quercetin-luteolin) was used. This study suggests the potential use of anthoxanthins as functional food ingredients to mitigate PPHG towards the management of T2DM.

Molecular dynamics simulations reveal the inhibitory mechanism of Withanolide A against α-glucosidase and α-amylase

Diabetes mellitus (DM) is a global chronic disease characterized by hyperglycemia and insulin resistance. The unsavory severe gastrointestinal side-effects of synthetic drugs to regulate hyperglycemia have warranted the search for alternative treatments to inhibit the carbohydrate digestive enzymes (e.g. α-amylase and α-glucosidase). Certain phytochemicals recently captured the scientific community's attention as carbohydrate digestive enzyme inhibitors due to their low toxicity and high efficacy, specifically the Withanolides-loaded extract of Withania somnifera. That said, the present study evaluated in silico the efficacy of Withanolide A in targeting both α-amylase and α-glucosidase in comparison to the synthetic drug Acarbose. Protein-ligand interactions, binding affinity, and stability were characterized using pharmacological profiling, high-end molecular docking, and molecular-dynamic simulation. Withanolide A inhibited the activity of α-glucosidase and α-amylase better, exhibiting good pharmacokinetic properties, absorption, and metabolism. Also, Withanolide A was minimally toxic, with higher bioavailability. Interestingly, Withanolide A bonded well to the active site of α-amylase and α-glucosidase, yielding the lowest binding free energy of −82.144 ± 10.671 kcal/mol and −102.1043 ± 11.231 kcal/mol compared to the Acarbose-enzyme complexes (−63.220 ± 13.283 kcal/mol and −82.148 ± 10.671 kcal/mol). Hence, the findings supported the therapeutic potential of Withanolide A as α-amylase and α-glucosidase inhibitor for DM treatment. Communicated by Ramaswamy H. Sarma

Revealing Anti-diabetic potential of Siddha formulation Gandhaka Sarkkarai using alpha amylase and alpha glucosidase enzyme inhibition assay

Background: Diabetes mellitus (DM) is a complex metabolic disorder which involves multiple pathology manifested with increased blood glucose, neural degeneration, chronic inflammation, organ dysfunction etc. Hyperactive metabolic enzymes like alpha amylase and alpha glucosidase that are involved in digestion of starch and sucrose further upswings the postprandial hyperglycaemia by rushing excess glucose moieties into the bloodstream. Drugs that effectively inhibit the action of these digestive enzymes may be expected to better regulate the post prandial blood glucose in the diabetic patients. Conventional anti-diabetic agents offer potential side effects upon long-term usage which includes vomiting, diarrhoea, pigmentation, GI disturbance, dark urination etc.The Siddha system of medicine has excelled in the art of treating human ailments for several centuries. Aim: Present investigation designed to investigate the anti-diabetic potential of siddha formulation Gandhaka sarkkarai (GS) using in-vitro alpha amylase and alpha glucosidase enzyme inhibition assay model. Results: It was evidenced from the outcome of the in-vitro data’s that the siddha formulation GS shown significant inhibition against alpha glucosidase enzyme with the maximum inhibition of about 50.44 % and the corresponding IC50 is 471.1 μg/ml, similar pattern of activity were observed against alpha amylase enzyme with the inhibition of 60.84 % (IC50 400.9 μg/ml). Conclusion: Our data concludes that siddha formulation GS possess significant anti-diabetic activity via inhibiting two major carbohydrate-digesting enzymes, further studies needs to extrapolated at pre-clinical level in order to ascertain the efficacy of the formulation.&#x0D; Key words: Diabetes mellitus, Alpha amylase, Alpha glucosidase, Siddha, Gandhaka sarkkarai, Enzyme inhibition assay, In-vitro, Anti-diabetic activity.

Assessment of Commercially Safflower Oils (Carthami Oleum Raffinatum) in Terms of European Pharmacopoeia Criteria and Their Weight Control Potentials.

Safflower oils, which are sold commercially, are in demand with food, cosmetics, and health-promoting claims. In this study, safflower oil samples belonging to 11 different brands were evaluated in terms of European Pharmacopoeia Criteria 7.0. Additionally, in vitro weight control potential of all samples was investigated. Samples to be analyzed were purchased from pharmacies, herbal, online, and cosmetics stores. Acid and peroxide values of 11 safflower samples and analysis of their fatty acids by gas chromatography-mass spectrometry (GC-MS) were carried out according to the "Carthami oleum raffinatum" monograph registered in the European Pharmacopeia 7.0. To test the effects of all samples on weight control, their inhibitory effects on carbohydrate-digesting enzymes (α-glucosidase and α-amylase) were evaluated using spectrophotometric methods. Out of 11 oil samples, only two of them had acid and peroxide values below the reference value. According to GC analysis, safflower oil samples are rich in monounsaturated fatty acids (oleic acid) and polyunsaturated fatty acids (linoleic acid) (67.10-99.53%) of total fatty acids in its content are oleic, linoleic, palmitic, and stearic acids. Saturated fatty acids were 0.58 to 12.18% of the total fatty acid methyl esters in oils. When evaluated in terms of the inhibition of α-amylase and α-glucosidase enzymes that hydrolyze carbohydrates, the results showed that safflower oil samples had no inhibitory activity on these enzymes. It has been determined in this report that many safflower oil samples on the market do not meet the quality criteria recommended in European Pharmacopoeia 7.0. It was observed that safflower oil did not show any inhibitory effect on these two enzymes, which is considered a rational approach for weight control.

Eryngium Species as a Potential Ally for Treating Metabolic Syndrome and Diabetes.

Medicinal plants possess natural compounds that can be used as an alternative for synthetic medicines that may cause long-term side effects on patients such as neurocognitive effects, muscular and hepatic toxicity. Metabolic Syndrome is associated with increased risk of several diseases such as diabetes, cardiovascular disease, dyslipidemia, and hypertension thus, becoming the greatest challenge as a growing public health concern worldwide. Latin-American countries possess a wide diversity of medicinal plants that have been used to treat different health conditions since pre-Hispanic times. Eryngium spp. has been studied due to their beneficial properties mainly to treat diabetes, dyslipidemia, blood pressure, and digestive problems. This review gives an update mainly on the pharmacological activities of the Eryngium spp., summarizing the biological activities and plausible mechanism of action of their bioactive components toward metabolic syndrome. For instance, flavonoids and tannins proved to increase the levels of HDL and reduced the levels of VLDL, LDL. On the other hand, phenolic acids improved glucose metabolism through the inhibition of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase (G6Pase) and reestablished the impaired activity of enzymes related to glucose oxidation and glycogen synthesis. The terpenes and sesquiterpenes like β-farnese, β-pinene, and calamenene exhibited a protective effect by reducing the oxidizing damage by the regulation of the Reactive Oxygen Species (ROS). Saponins controlled the dyslipidemia by reducing the serum concentrations of lipids, triglycerides and total cholesterol. Finally, the aerial parts of Eryngium had the capacity of inhibiting dietary carbohydrate digestive enzymes, thus controlling glucose levels. The Eryngium plant is normally consumed as an infusion to obtain the benefits of the plants, however novel technologies such as cavitation, ultrasound assisted, microwave assisted, and supercritical fluid have been applied to improve the extraction yields and selectivity of bioactive compounds. The common treatment to control diabetic dyslipidemia are synthetic medicines such as metformin and ezetimibe, which allows the regulation of glucose, cholesterol and insulin resistance. However, patients that take these medications may present side effects such as muscular toxicity, hepatic toxicity, neurocognitive effects, just to name a few. More studies regarding the efficacy and safety of the use of traditional medicinal herbs are required. However, these materials may be used in the treatment of diabetes related conditions to ensure life quality and reduce side effects among the diabetic population

Piper nigrum and Morinda lucida Possess Antioxidant Capacities and Regulate the Activities of Key Carbohydrate and Lipid Digestive Enzymes

Introduction: Carbohydrate and lipid digestive enzymes are instrumental in the absorbability of nutrients associated to diabetes and obesity. This study evaluated hydroethanolic extracts of Piper nigrum leaf and Morinda lucida stem bark for antioxidant capacity and enzymes (carbohydrate and lipid digestive) inhibition.&#x0D; Methods: Colorimetric assays determined enzyme (α-amylase, α-glucosidase, lipase and cholesterol esterase) inhibition and antioxidant capacity (total phenolic (TPC) and flavonoid (TFC) content, radical scavenging activity (DPPH, ABTS), and ferric reducing antioxidant power (FRAP)) of hydroethanolic ethanolic extracts, ethyl acetate and hexane fractions.&#x0D; Results: At 1 mg/ml extracts of P nigrum and M lucida inhibited α- amylase (9.82±1.05 - 36.63±0.69 %) and α-glucosidase (22.47±0.34 - 67.77±0.58 %) activities. At 100 µg/ml extracts and fractions inhibited lipase (56.72±1.11 - 81.61±0.71 %) and cholesterol esterase (18.14 ±0.79 - 36.84±0.70 %) activities. IC50 for α- amylase (2.20±0.02 - 7.8±1.42 mg/ml), α-glucosidase (0.16±0.01 - 3.74±0.01 mg/ml), lipase (8.58±2.57 - 53.03±5.20 µg/ml) and cholesterol esterase (172.20±5.12 - 419.80±4.55 µg/ml) were registered. At 4 mg/ml, P. nigrum presented a higher TPC (153.78±8.31 - 354.63±6.33 mg/ml), TFC (21.65±1.14 -33.86±0.00 mg/ml) than M lucida TPC (10.21±0.11 - 169.89±6.54 mg/ml), TFC (ND - 87.32±6.14 mg/ml). P nigrum presented radical scavenging (DPPH and ABTS) activity with IC50 0.12±0.00 - 1.27±0.01 mg/ml compared to 1.31±0.02 - 3.44±0.12 mg/ml of M lucida. The FRAP IC50 values were better for P nigrum (3.38±0.14- 4.48±1.05 mg/ml) than M lucida (3.34±1.32 - 15.4±2.03 mg/ml).&#x0D; Conclusion: P nigrum presented better antioxidant capacity and more effective on lipid digestive enzymes while M lucida was more effective on carbohydrate digestive enzymes.

Newly described antioxidant disecolactonic ergosteroids from marine cuttlefish Sepia pharaonis: Pharaonoids A-B as prospective carbohydrate digestive enzyme inhibitors

Biochemical investigation of crude solvent extract of pharaoh cuttlefish Sepia pharaonis (family Sepiidae) led to the isolation of two undescribed disecolactonic ergosteroids, pharaonoids A-B. The compounds were characterized as 11β-acteoxy-7α-hydroxy-19-Nor-1,10:9,10-disecoergosta-3-ene-61-oxa-1-one (pharaonoid A) and 11β-hydroxy-19-Nor-1,10:9,10-disecoergosta-3-ene-61-oxa-1-one (pharaonoid B) in conjunction with spectroscopic analysis encompassing one and two-dimensional nuclear magnetic resonance and mass spectrometric analyses. Pharaonoid A, bearing an acetoxy and hydroxyl groups, respectively at C-11 and C-7 positions exhibited considerably greater inhibition potential against carbohydrate hydrolysing enzymes α-amylase (IC50 1.14 mM) and α-glucosidase (IC50 1.23 mM) than those displayed by pharaonoid B (IC50 1.49/1.38 mM), and was proportionate with those exhibited by standard drug acarbose (IC50 0.60 and 0.40 mM, respectively), thereby recognizing the anti-hyperglycemic potential of pharaonoid A. Promising anti-oxidant property for pharaonoid A (IC50 ∼ 1 mM) could conceivably corroborate its attenuation potential against carbohydrate digestive enzymes. Greater electronic parameters along with optimum lipophilic-hydrophobic balance of pharaonoid A were directly corroborated to the anti-carbolytic properties occurring via transcellular mechanism. Greater binding energies (−9.50 kcal mol−1) and inhibition constant (Ki 48.21 nM) at the active site of α-amylase enzyme were displayed by pharaonoid A than those exhibited by its B analogue. Promising bioactive properties of the disecolactonic steroids isolated from the marine pharaoh cuttlefish are anticipated to be utilized as functional food components and potential nutraceuticals against oxidative stress and hyperglycemic disorders.

A Review of the Effectiveness Natural Pigment as Antidiabetic to Decrease the Significant Risk For COVID-19 Disease

Diabetes mellitus proved to be a significant risk factor for both COVID-19 infection and poor outcomes among these chronic health problems. Plants are a rich source of chemical components that could block carbohydrate digestion enzymes, and they can be utilized as therapeutic or functional foods. Natural pigments that have potential benefits, such as chlorophyll, anthocyanin as a part of flavonoid, and carotenoid. Chlorophylls are the most significant and widespread pigment molecules in nature, and they are required for photosynthesis to occur. Anthocyanins are the most important group of water-soluble pigments in plants, responsible for the red, purple, and blue colors of many fruits, vegetables, cereal grains, and flowers. Carotenoids, natural pigments found in an array of different foodstuffs, are the most abundant pigments present in the human diet. The most frequent method for determining a substance's antidiabetic potential is to assess the substance's hypoglycemic or antihyperglycemic.

Insights into the leaves of Ceriscoides campanulata: Natural proanthocyanidins alleviate diabetes, inflammation, and esophageal squamous cell cancer via in vitro and in silico models

Fourteen flavones (1–14) including twelve polymethoxylated flavones, two A-type proanthocyanidins (oligomeric flavonoids) (15, 16), one benzoyl glucoside (17), one triterpenoid (18), and one phenylpropanoid (19) were isolated from the leaves of the South Asian medicinal plant Ceriscoides campanulata (Roxb.) Tirveng (Rubiaceae). The structures of the compounds were identified based on their spectroscopic and spectrometric data and in comparison with literature data. Isolated compounds were tested in vitro against inflammatory enzymes (COX-2, iNOS), pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), esophageal squamous carcinoma cell line (TE13), and carbohydrate digestion enzymes (α-amylase, α-glucosidase). Proanthocyanidins 15 and 16 significantly attenuated the LPS-induced inflammatory response of COX-2, iNOS, IL-1β, IL-6, TNF-α in RAW 264.7 cells. Proanthocyanidins also satisfactorily inhibited the regrowth (64%), migration (51%), and formation of tumor-spheres (48%) in ESCC cell line TE13 at 50% toxic concentration. Compounds 15 and 16 showed the most potent effect against mammalian α-amylase (IC50 8.4 ± 0.3 μM and 3.5 ± 0.0 μM, respectively) compared to reference standard acarbose (IC50 5.9 ± 0.1 μM). As yeast α-glucosidase inhibitors, compounds 15 and 16 also displayed significant activities (IC50 6.2 ± 0.3 and 4.7 ± 0.1 μM, respectively), while compounds 1–6 displayed weaker α-glucosidase inhibitory activities, ranging from 49 to 142 μM, compared to acarbose (IC50 665 ± 42 μM). In an anticholinesterase assay, compounds 1, 2, 6 (IC50 51 ± 2, 53 ± 7, 64 ± 5 μM, respectively), and 4 (IC50 44 ± 1 μM) showed moderate inhibitory activities against acetylcholinesterase and butyrylcholinesterase, respectively. Furthermore, molecular docking and molecular dynamic simulation analyses of compounds 15 and 16 were performed against human pancreatic α-amylase and human lysosomal acid α-glucosidase to elucidate the interactions of these compounds in the respective enzymes' active sites.

Phenolic Bioactives From Plant-Based Foods for Glycemic Control.

Plant-based foods containing phenolic bioactives have human health protective functions relevant for combating diet and lifestyle-influenced chronic diseases, including type 2 diabetes (T2D). The molecular structural features of dietary phenolic bioactives allow antioxidant functions relevant for countering chronic oxidative stress-induced metabolic breakdown commonly associated with T2D. In addition to antioxidant properties, phenolic bioactives of diverse plant foods have therapeutic functional activities such as improving insulin sensitivity, reducing hepatic glucose output, inhibiting activity of key carbohydrate digestive enzymes, and modulating absorption of glucose in the bloodstream, thereby subsequently improving post-prandial glycemic control. These therapeutic functional properties have direct implications and benefits in the dietary management of T2D. Therefore, plant-based foods that are rich in phenolic bioactives are excellent dietary sources of therapeutic targets to improve overall glycemic control by managing chronic hyperglycemia and chronic oxidative stress, which are major contributing factors to T2D pathogenesis. However, in studies with diverse array of plant-based foods, concentration and composition of phenolic bioactives and their glycemic control relevant bioactivity can vary widely between different plant species, plant parts, and among different varieties/genotypes due to the different environmental and growing conditions, post-harvest storage, and food processing steps. This has allowed advances in innovative strategies to screen and optimize whole and processed plant derived foods and their ingredients based on their phenolic bioactive linked antioxidant and anti-hyperglycemic properties for their effective integration into T2D focused dietary solutions. In this review, different pre-harvest and post-harvest strategies and factors that influence phenolic bioactive-linked antioxidant and anti-hyperglycemic properties in diverse plant derived foods and derivation of extracts with therapeutic potential are highlighted and discussed. Additionally, novel bioprocessing strategies to enhance bioavailability and bioactivity of phenolics in plant-derived foods targeting optimum glycemic control and associated T2D therapeutic benefits are also advanced.

Antioxidant activity and inhibitory efficacy of Citrus grandis peel extract against carbohydrate digestive enzymes in vitro

Citrus peel extract has been observed with many beneficial-promoting effects. Pomelo (Citrus grandis (L) Osbeck) peel extracts (PPE) from the flavedo and albedo of two varieties namely Long Co Co and Thanh Kieu were investigated. In this study, the qualitative analysis indicated the presence of phytochemical groups including alkaloids, flavonoids, saponins, and tannin in the PPE from the flavedo and albedo. The PPE from the Thanh Kieu flavedo was found to possess the highest antioxidant activity at the EC50 values of 60.89 ± 0.31 µg/mL, 60.69 ± 0.21 µg/mL, and 24.16±0.06 µg/mL for DPPH, ABTS, and FRAP assay. However, the Long Co Co albedo- PPE induced better inhibitory effect against α-amylase (EC 232-560-9) and α-glucosidase (EC 232-604-7) with respect to EC50 values of 3.59 ± 0.02 mg/mL and 80.77 ± 0.34 µg/mL. This result suggested potential in the anti-hyperglycemic effect of pomelo peel extract from the flavedo and albedo that can serve as a nutraceutical in food and pharmaceutical industries.

In vitro α-glucosidase enzyme inhibition and anti-inflammatory studies of Mn3O4 nanoparticles mediated using extract of Dalbergiella welwitschia

α-glucosidase is a carbohydrate digestive enzyme that increases the postprandial glucose level in many patients living with diabetes. Inhibiting its activity can reduce or control the possibilities for postprandial hyperglycemia and diabetes. In this study, we studied the potential of Dalbergiella welwitschia mediated trimanganese tetraoxide (Mn3O4) nanoparticles (NPs) as a potential inhibitory agent against α-glucosidase enzyme and the usually accompanied subclinical inflammation that may become fostered due to increased sugar level. The Mn3O4 nanoparticles were prepared using Dalbergiella welwitschia leaf extract as a renewable, mild, non-toxic reducing agent and efficient stabilizer. The phase, morphological structure, particle size, and purity of the synthesized Mn3O4 nanoparticles were evaluated using X-ray diffraction, scanning and transmission electron microscope, and energy-dispersive X-ray spectroscopy analysis. These XRD analyses confirmed the hausmannite phase of Mn3O4 NPs with no impurities. The prepared Mn3O4 NPs were spherically shaped, and the sizes were between 35 and 40 nm, with an average size of 35.58 nm. The studies of the α-glucosidase inhibition and anti-inflammatory properties of the synthesized Mn3O4 NPs were found to possess a minimum inhibitory concentration (IC50) value of 2.50 mg/mL and 3.11 µM in both in vitro α-glucosidase and bovine serum assays respectively. These values are slightly lower than the standard drugs of metformin and diclofenac, with IC50 of 1.87 mg/mL and 2.79 µM, respectively. Nevertheless, the closeness of the IC50 values of the samples to the standard drugs in both studies showed that the Mn3O4 NPs have potential as antidiabetic and anti-inflammatory agents.

Polyherbal formulation improves glucose-lipid metabolism and prevent hepatotoxicity in streptozotocin-induced diabetic rats: Plausible role of IRS-PI3K-Akt-GLUT2 signaling

Background: Type 2 diabetes mellitus is a progressive polygenic disorder requiring a multi-targeted therapeutic approach. A polyherbal formula (PHF) comprised of four traditional herbs known for their anti-diabetic, anti-oxidant, and hepatoprotective activities were used in this study. Objectives: The purpose of this research was to find out the plausible mechanisms underlying the synergistic effects of PHF in an experimental setting of diabetes mellitus. Materials and Methods: PHF was evaluated for the presence of residual toxins, acute oral toxicity, and its effects on carbohydrate digestive enzymes. PHF (100, 200, and 300 mg/kg/p. o., respectively) was used to treat streptozotocin-induced diabetic rats for 12 weeks followed by glycemic, histopathological, biochemical, and ultrastructural changes measurement. mRNA levels of AMPK, insulin receptor substrate (IRS), phosphoinositide-3-phosphate kinase (PI3K), Akt, and glucose transporter 2 (GLUT2) were measured using real-time polymerase chain reaction. Results: In PHF, the residual toxins were absent. PHF inhibited the α-amylase (IC50 152.2 ± 9.3 μg/mL), and α-glucosidase (IC50 103.0 ± 0.81 μg/mL) activities in-vitro. Further, up to a dose of 2000 mg/kg, PHF showed no signs of mortality. PHF treatment significantly maintained the glycemic state, antioxidant status, lipid profile, hepatic-architecture, and ultrastructural alterations in diabetic rats. Similarly, diabetic rats showed detrimental effects on the mRNA level of AMPK and IRS-PI3K-Akt-GLUT2 signaling which were attenuated by PHF treatment. Immunohistochemical analysis also revealed an improvement in p-Akt expression after PHF treatment. Conclusion: In streptozotocin-induced diabetic rats, PHF improves glucose and lipid metabolism by attenuating hyperglycemia, hyperinsulinemia, dyslipidemia, insulin resistance, oxidative stress, inflammation, and deterioration of hepatic architecture possibly through AMPK mediated improvement in hepatic IRS-PI3K-Akt-GLUT2 signaling pathway.

Harpephyllum caffrum stimulates glucose uptake, abates redox imbalance and modulates purinergic and glucogenic enzyme activities in oxidative hepatic injury

Objective: To investigate the antioxidative and antidiabetic effects of Harpephyllum caffrum bark infusion as well as its effects on glucogenic and nucleotide hydrolyzing enzyme activities in FeSO4- induced oxidative stress in rat hepatic tissue.Methods: Harpephyllum caffrum infusion was prepared from dried plant materials (40 g) infused in boiling water (400 mL) for 20 min at room temperature. The antioxidative and inhibitory activities against carbohydrate digestive enzymes of the infusion were determined using established protocols. The liver tissues of rats were used for glucose uptake assay and to evaluate the infusion’s effect on endogenous antioxidant, glucogenic, and nucleotide hydrolyzing enzyme activities in FeSO4-induced hepatic injury.Results: The Harpephyllum caffrum infusion significantly reduced ferric iron (FRAP) and free radicals (OH• and DPPH) in a dose- dependent manner. It inhibited α-amylase and α-glucosidase activities and increased glucose uptake in hepatic tissues. FeSO4 significantly decreased glutathione concentration, catalase, and superoxide dismutase activities while increasing malondialdehyde level, glycogen phosphorylase, fructose-1,6-bisphosphatase, and adenosine triphosphatase activities. However, treatment with Harpephyllum caffrum infusion reversed FeSO4-induced changes. Characterization of the infusion revealed the presence of catechol, O-pyrocatechuic acid, mequinol, maltol, and glycoside derivatives.Conclusions: The Harpephyllum caffrum infusion demonstrates antidiabetic and antioxidative potentials in in vitro models of type 2 diabetes as depicted by its ability to inhibit carbohydrate digestive enzymes, mitigate oxidative imbalance, and regulate glucogenic and nucleotide hydrolyzing enzyme activities in oxidative hepatic injury.

Senna petersiana inhibits key digestive enzymes and modulates dysfunctional enzyme activities in oxidative pancreatic injury

Objective: To evaluate the effect of Senna petersiana leaf extracts on key digestive enzymes and FeSO4-induced oxidative injury.Methods: Dried Senna petersiana leaf powder (60 g) was defatted in n-hexane and then extracted sequentially at room temperature with dichloromethane, methanol, and distilled water. The total phytochemical content of the extracts was estimated using established methods. The in vitro antioxidant, anti-lipase, and antidiabetic activities and the effect of the extracts on intestinal glucose absorption and FeSO4-induced pancreatic oxidative injury were determined using different protocols. Moreover, GC-MS analysis was performed to identify the main compounds of the plant extract. Molecular docking analysis was also carried out to evaluate the binding energy of compounds with digestive enzymes.Results: Senna petersiana leaf extracts showed significant antioxidant activities in FRAP, DPPH, and hydroxyl radical scavenging assays. They also inhibited pancreatic lipase and lowered intestinal glucose absorption by suppressing activities of α-amylase and α-glucosidase. Treatment with the extracts also lowered lipid peroxidation (malondialdehyde), nitric oxide level, acetylcholinesterase, and ATPase activities with simultaneous improvement of antioxidant (catalase, superoxide dismutase, glutathione) capacity in the type 2 diabetes model of oxidative pancreatic injury. GC-MS characterization of the extracts revealed the presence of stilbenoids, alkaloids, and other compounds. Molecular docking screening assay indicated the extract phytochemicals showed strong interaction with the active site amino acids of the targeted digestive enzymes. Among the Senna petersiana compounds, veratramine had the highest affinity for α-amylase and lipase, whereas dihydrostilbestrol was most attracted to α-glucosidase.Conclusions: Senna petersiana inhibits carbohydrate digestive enzymes, reduces intestinal glucose absorption, and exerts ameliorative effects on FeSO4-induced oxidative pancreatic injury with significant antioxidant capabilities. Detailed in vivo studies are underway to understand the plant’s therapeutic potential in diabetes management.