Potential Antidiabetic Agents Research Articles

Computational Screening for the Dipeptidyl Peptidase-IV Inhibitory Peptides from Putative Hemp Seed Hydrolyzed Peptidome as a Potential Antidiabetic Agent.

Dipeptidyl peptidase-IV (DPPIV) inhibitory peptides are a class of antihyperglycemic drugs used in the treatment of type 2 diabetes mellitus, a metabolic disorder resulting from reduced levels of the incretin hormone GLP-1. Given that DPPIV degrades incretin, a key regulator of blood sugar levels, various antidiabetic medications that inhibit DPPIV, such as vildagliptin, sitagliptin, and linagliptin, are employed. However, the potential side effects of these drugs remain a matter of debate. Therefore, we aimed to investigate food-derived peptides from Cannabis sativa (hemp) seeds. Our developed bioinformatics pipeline was used to identify the putative hydrolyzed peptidome of three highly abundant proteins: albumin, edestin, and vicilin. These proteins were subjected to in silico digestion by different proteases (trypsin, chymotrypsin, and pepsin) and then screened for DPPIV inhibitory peptides using IDPPIV-SCM. To assess potential adverse effects, several prediction tools, namely, TOXINpred, AllerCatPro, and HemoPred, were employed to evaluate toxicity, allergenicity, and hemolytic effects, respectively. COPID was used to determine the amino acid composition. Molecular docking was performed using GalaxyPepDock and HPEPDOCK, 3D visualizations were conducted using the UCSF Chimera program, and MD simulations were carried out with AMBER20 MD software. Based on the predictive outcomes, FNVDTE from edestin and EAQPST from vicilin emerged as promising candidates for DPPIV inhibitors. We anticipate that our findings may pave the way for the development of alternative DPPIV inhibitors.

Amino Acid Compositions and In vitro Anti-inflammatory Properties of Cookies Produced from Wheat and Soybean Composite Flour

Composite flours were formulated from wheat and soybean and mixed together to formulate four blends WSY 1 (100%), WSY 2 (80%-20%), WSY 3 (70%-30%), WSY 4 (60%-40%), respectively to bake cookies. The cookies were investigated for their amino acid profiles, in vitro anti-inflammatory properties and consumer acceptability of the cookies using standard methods. The amino acid profiles of the cookies were well established with high biological values (>70%) in terms of their essential, non-essential and hydrophobic amino acids while glutamic acid served as the most abundant amino acid (19.15 – 28.69%) present in each of the cookies. Moreso, the in-vitro anti-inflammatory properties of the cookies showed more potency with low IC50 (~20 \(\mu\)g/ml) than the standard sodium diclofenac, a well-known non-steroidal anti-inflammatory drug. Overall, the cookie sample from the 60% wheat and 40% soybean composite flour was acceptable to the consumers as shown by their ratings and perceptions, which could be highly found useful as potential bioactive antioxidant, anti-diabetic and anti-inflammatory agents in the management of chronic inflammations.

Diabetes Warriors from Heart Wood: Unveiling Dalbergin and Isoliquiritigenin from Dalbergia latifolia as Potential Antidiabetic Agents in-vitro and in-vivo.

Diabetes mellitus is a serious and complex metabolic disorder characterized by hyperglycemia. In recent years natural products has gained much more interest by researchers as alternative sources for diabetes treatment. Though many potential agents are identified so far but their clinical utility is limited because of their adverse effects. Therefore, there is a keen interest in discovering natural compounds to treat diabetes efficiently with less side effects. Dalbergia latifolia is well explored because of its diverse pharmacological activities including diabetes. Therefore, the present research work aimed to identify and isolate the potential antidiabetic agents from the heart wood of Dalbergia latifolia. We successfully extracted DGN and ISG from the heartwood and evaluated their antidiabetic potential both in-vivo and in-vitro. Alpha amylase activity inhibition of ISG and DGN was found to be 99.05 ± 8.54% (IC50 = 0.6025 µg/mL) and 84.68 ± 5.2% (IC50 = 0.0216 µg/mL) respectively. Glucose uptake assay revealed DGN (158%) promoted maximum uptake than ISG (77%) over control. In vivo anti diabetic activity was evaluated by inducing diabetes in SD rats with the help of HFD and STZ (35 mg/kg body weight). After the continuous administration of DGN (5 mg/kg, 10 mg/kg) and ISG (5 mg/kg, 10 mg/kg) for 14 days, we observed the reduction in the blood glucose levels, body weight, total cholesterol, low density lipoprotein, very low-density lipoprotein, blood urea, serum creatinine, serum glutamate oxaloacetic transaminase, serum glutamate pyruvate transaminase and alkaline phosphatase levels than vehicle group indicates the potency of ISG and DGN against diabetes.

Antidiabetic and antihyperlipidemic effects of crude fractions from Chlorophytum borivilianum root methanolic extract on streptozotocin induced diabetic rats and phytochemical investigation by LCMS analysis.

To evaluate the in vitro and in vivo pharmacological efficacy of the plant Chlorophytum borivilianum in diabetes and hyperlipidemia and to confine and describe the synthetic constituents from the roots that are in charge of the action. The present study was carried out to investigate the ethno-medical use of Chlorophytum borivilianum root methanolic extract as a potential anti-diabetic and antihyperlipidemic agent in STZ-induced diabetic rats. Extract was tested for in vitro and in vivo biological activities. Soxhlet extraction was carried out using methanol as a solvent, and TLC and column chromatography were used for fractionation. Liquid Chromatography and Mass Spectroscopic study confirmed the structures of isolated compounds. Chlorophytum borivilianum root methanolic extract showed the presence of phytoconstituents as Dihydrocapsaicin, Reserpine, Deserpidine, Biliverdin-IX-α, and Cassiamin C having a therapeutic effect. Dihydrocapsaicin was identified at RT 7.572 and the Chlorophytum borivilianum root chloroform methanolic extract fraction noticeably depleted increased blood glucose levels and had positive effects on altered lipid profile after administering a dose of 150 mg/kg orally compared with oral hypoglycemic drug metformin. All the results are dose-dependent. Active chloroform-methanol fraction from methanol extract showed the presence of anti-diabetic compound, Dihydrocapsaicin. The chloroform-methanol fraction from the methanolic extract of Chlorophytum borivilianum root can inhibit the parameters linked to diabetes and hyperlipidemia.

Thiosemicarbazone derivatives as potent antidiabetic agents: Synthesis, in vitro, molecular docking and DFT investigations

A library of thiosemicarbazones derivatives have been synthesized by multi step reactions, characterized and screened for their in vitro α-amylase and α-glucosidase inhibitory actions. Among them, three compounds including 4b (IC50 = 3.18 ± 1.72 and 2.11 ± 1.29 µM), 4a (IC50 = 5.16 ± 1.12 and 7.23 ± 0.11 µM), and 4 g (IC50 = 7.13 ± 1.21 and 9.53 ± 0.29 µM) are found as potential dual inhibitors of α-amylase and α-glucosidase enzymes, powerfull than the standard acarbose drug (IC50 = 21.55 ± 1.31 and 16.65 ± 0.07 µM). In addition, compounds 4c, 4f, 4 h, 4d, and 4e indicated significant to less inhibitory potential. Molecular docking was performed to know the binding affinities and various interactions between the synthesized compounds and targeted proteins. For the docking analysis, the protein structure of α-amylase was taken from the Protein Data Bank (PDB) with the code 3BAJ, derived from Homo sapiens. Meanwhile, the protein structure of α-glucosidase was obtained from Beta vulgaris with the PDB code 3W37. The chemical nature of the product compounds was identified using the density functional theory (DFT) method, and the calculations were performed using the B3LYP/6–311++G(d,p) method. Intramolecular interactions were explored using DFT-d3 and Reduced Density Gradient (RDG) analysis. Furthermore, the chemical nature of all the compounds was identified using TD-DFT at the CAM-B3LYP/6–311++G(d,p) method. Among the synthesized compounds, 4a, 4b, and 4g show similar inhibition activities with targeted proteins. Similar activities have been confirmed using the TD-DFT method. The energy gap between the highest occupied molecular orbitals and lowest unoccopied was found as, 6.07, 6.08, and 6.07 eV, respectively. The similarty in energy gap indicated these compounds have similiar reactivity nature.

Synthesis and molecular docking studies of new aryl imeglimin derivatives as a potent antidiabetic agent in a diabetic zebrafish model

Diabetes mellitus (DM) is a persistent, progressive, and multifaceted disease characterized by elevated blood glucose levels. Type 2 diabetes mellitus is associated with a relative deficit in insulin mainly due to beta cell dysfunction and peripheral insulin resistance. Metformin has been widely prescribed as a primary treatment option to address this condition. On the other hand, an emerging glucose-reducing agent known as imeglimin has garnered attention due to its similarity to metformin in terms of chemical structure. In this study, an innovative series of imeglimin derivatives, labeled 3(a–j), were synthesized through a one-step reaction involving an aldehyde and metformin. The chemical structures of these derivatives were thoroughly characterized using ESI–MS, 1H, and 13C NMR spectroscopy. In vivo tests on a zebrafish diabetic model were used to evaluate the efficacy of the synthesized compounds. All compounds 3(a–j) showed significant antidiabetic effects. It is worth mentioning that compounds 3b (FBS = 72.3 ± 7.2 mg/dL) and 3g (FBS = 72.7 ± 4.3 mg/dL) have antidiabetic effects comparable to those of the standard drugs metformin (FBS = 74.0 ± 5.1 mg/dL) and imeglimin (82.3 ± 5.2 mg/dL). In addition, a docking study was performed to predict the possible interactions between the synthesized compounds and both SIRT1 and GSK-3β targets. The docking results were in good agreement with the experimental assay results.

Purification of exopolysaccharide produced from Lactobacillus spp. using ionic-liquid as adjuvant in alcohol/salt-based aqueous two-phase system for its antidiabetic properties

Diabetes is a chronic, metabolic disease characterized by hyperglycemia resulting from either insufficient insulin production or impaired cellular response to insulin. Exopolysaccharides (EPS) produced by Lactobacillus spp. demonstrated promising therapeutic potential in terms of their anti-diabetic properties. Extraction and purification of EPS produced by Lactobacillus acidophilus and Limosilactobacillus reuteri were performed using ethanol precipitation, followed by alcohol/salt based aqueous two-phase system (ATPS). The purification process involved ethanol precipitation followed by an alcohol/salt-based ATPS. The study systematically investigated various purification parameters in ATPS, including ethanol concentration, type and concentration of ionic liquid, type and concentration of salt and pH of salt. Purified EPS contents from L. acidophilus (63.30 μg/mL) and L. reuteri (146.48 μg/mL) were obtained under optimum conditions of ATPS which consisted of 30 % (w/w) ethanol, 25 % (w/w) dipotassium hydrogen phosphate at pH 10 and 2 % (w/w) 1-butyl-3-methylimidazolium octyl sulfate. The extracted EPS content was determined using phenol sulphuric acid method. In α-amylase inhibition tests, the inhibitory rate was found to be 92.52 % (L. reuteri) and 90.64 % (L. acidophilus), while in α-glucosidase inhibition tests, the inhibitory rate was 73.58 % (L. reuteri) and 68.77 % (L. acidophilus), based on the optimized parameters selected in ATPS. These results suggest that the purified EPS derived from the postbiotics of Lactobacillus spp. hold promise as potential antidiabetic agents.

Characterization of Plant-Derived Natural Inhibitors of Dipeptidyl Peptidase-4 as Potential Antidiabetic Agents: A Computational Study.

Diabetes, characterized by elevated blood sugar levels, poses significant health and economic risks, correlating with complications like cardiovascular disease, kidney failure, and blindness. Dipeptidyl peptidase-4 (DPP-4), also referred to as T-cell activation antigen CD26 (EC 3.4.14.5.), plays a crucial role in glucose metabolism and immune function. Inhibiting DPP-4 was anticipated as a potential new therapy for diabetes. Therefore, identification of plant-based natural inhibitors of DPP-4 would help in eradicating diabetes worldwide. Here, for the identification of the potential natural inhibitors of DPP-4, we developed a phytochemicals library consisting of over 6000 phytochemicals detected in 81 medicinal plants that exhibited anti-diabetic potency. The library has been docked against the target proteins, where isorhamnetin, Benzyl 5-Amino-5-deoxy-2,3-O-isopropyl-alpha-D-mannofuranoside (DTXSID90724586), and 5-Oxo-7-[4-(trifluoromethyl) phenyl]-4H,6H,7H-[1,2]thiazolo[4,5-b]pyridine 3-carboxylic acid (CHEMBL3446108) showed binding affinities of -8.5, -8.3, and -8.3 kcal/mol, respectively. These compounds exhibiting strong interactions with DPP-4 active sites (Glu205, Glu206, Tyr547, Trp629, Ser630, Tyr662, His740) were identified. ADME/T and bioactivity predictions affirmed their pharmacological safety. Density functional theory calculations assessed stability and reactivity, while molecular dynamics simulations demonstrated persistent stability. Analyzing parameters like RMSD, RG, RMSF, SASA, H-bonds, MM-PBSA, and FEL confirmed stable protein-ligand compound formation. Principal component analysis provided structural variation insights. Our findings suggest that those compounds might be possible candidates for developing novel inhibitors targeting DPP-4 for treating diabetes.

Isolation, Characterization and Structure Elucidation of Antidiabetic Compound “2-({4-oxo-1H,2H,3H,4H,4aH-cyclopenta[b]pyridine-2-yl} methyl)-1H, 2H, 3H, 4H, 4aH-Cyclopenta[b]Pyridine-4-one” from the barks of Parkia timoriana (DC.) Merr.

Parkia timoriana (D.C.) Merr is a medicinal plant with long-known usage as a traditional medicine. This plant’s bark and pods have been used in medicine and food supplements. P. timoriana bark was extracted with ethyl acetate and purified using silica gel column chromatography. A pure compound, 2-({4-oxo-1H, 2H, 3H, 4H, 4aH-cyclopenta[b]pyridine-2-yl}methyl)-1H, 2H, 3H, 4H, 4Ah cyclopenta[b]pyridine-4-one (BCPP) was isolated and spectroscopic analysis was performed to determine its chemical structure. Antidiabetic studies were conducted using Bis-Cyclopenta-Pyridin (BCPP) for its enzymatic inhibition. In vitro cell culture assays, gene expression studies and in silico docking studies were done to ascertain the antidiabetic activity. P. timoriana bark was extracted using the solvents based on its polarity: hexane, ethyl acetate and methanol. At a 125 μg/ml concentration, BCPP demonstrated 75% inhibition of alpha-amylase, 74% inhibition of alpha-glucosidase and a 59% increase in glucose uptake by yeast cells (3.3 ± 0.0058 at 125 μg/ml). BCPP increased the expression of the PPARγ gene in 3T3-L1 cells by 0.23-fold. There is an increase in fold change of PPAR- γ at 25 μg/ml – 0.11-fold; at 50 μg /ml – 0.25-fold; at 75 μg /ml – 0.37-fold; 100 μg /ml – 0.73-fold; and at 125 μg/ml, there is an upregulation of 1.10-fold in 3T3-L1 cells. In silico docking studies confirmed the alpha-amylase and alpha-glucosidase inhibitory activities of BCPP. This study suggests the application of BCPP as a potential antidiabetic agent that can be used in drug design and pharmaceutics.

Synthesis, Glucosidase Inhibition, and In Silico Modeling Analysis of Highly Fluorinated 2-Imino-1,3-thiazolines in Search of Potent Antidiabetic Agents.

In the present work, 2-imino-1,3-thiazolines featuring highly fluorinated fragments were synthesized through a straightforward cyclization of diversely substituted thioureas with 2-bromo-1-(4-fluorophenyl)ethan-1-one. The target compounds were obtained in good yields, and structures were established by FTIR and 1H- and 13C NMR spectroscopic methods. The in vitro biological assay revealed that all the compounds significantly obstruct the α-glucosidase. Compound 6d (3-fluoro-N-(3-(2-fluorophenyl)-4-(4-fluorophenyl)thiazol-2(3H)-ylidene)benzamide) showed the highest antidiabetic potential with an IC50 value of 1.47 ± 0.05 μM. In addition, computational analysis revealed the binding energy of -11.1 kcal/mol for 6d which was lower than the positive standard, acarbose (-7.9 kcal/mol). Several intermolecular interactions between the active site residues and 6d highlight the significance of 2-imino-1,3-thiazoline core in attaining the potent efficacy and making these compounds a valuable pharmacophore in drug discovery.

Anti-diabetic effect of <i>Eucalyptus camaldulensis</i> (Red gum) leaf-supplemented diet in streptozotocin-induced diabetic rats

Purpose: To investigate the potential anti-diabetic effect of supplementing a diet with Eucalyptus camaldulensis leaves in streptozotocin (STZ) induced Wistar rats. 
 Methods: Methanolic extract of E. camaldulensis was screened using gas chromatography-mass spectrometric analysis. After that, eighteen animals were separated into three groups: Group A served as control group. Group B, the diabetic control group, was induced with STZ, and Group C was induced with STZ and fed a 10 % E. camaldulensis leaf-supplemented diet for 14 days. Thereafter, rats were sacrificed, and fasting blood was collected for serum glucose, enzyme and protein activity tests. Organs were excised for biochemical and histological analysis. 
 Results: The GC-MS fingerprint identified 17 constituents, with 2-hydroxy carbazole being the most abundant. Rats on the E. camaldulensis leaf-based diet for 14 days exhibited a significant decrease (p < 0.05) in serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, albumin, total bilirubin, urea, and creatinine concentrations compared to diabetic controls. Insulin levels significantly increased (p < 0.05). Additionally, the E. camaldulensis diet led to a significant decrease in serum lipid profile levels but increased high-density lipoprotein cholesterol (HDL-C). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased significantly, while malondialdehyde levels decreased significantly (p < 0.05). Histopathology revealed positive effects on hepatocytes, acini, pancreatic duodenal lymphoid activation, islets of Langerhans resurgence, and normal kidneys. 
 Conclusion: Eucalyptus camaldulensis leaf-supplemented diet demonstrates anti-diabetic, hypolipidemic and antioxidant enzyme activities. Carbazole identified by GC-MS may be the potential anti-diabetic and hypolipidemic agent in E. camaldulensis leaf-based diet.

Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers.

A series of 3-substituted and 3,5-disubstituted rhodanine-based derivatives were synthesized from 3-aminorhodanine and examined for α-amylase inhibitory, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities in vitro. These derivatives displayed significant α-amylase inhibitory potential with IC50 values of 11.01-56.04 µM in comparison to standard acarbose (IC50 = 9.08 ± 0.07 µM). Especially, compounds 7 (IC50 = 11.01 ± 0.07 µM) and 8 (IC50 = 12.01 ± 0.07 µM) showed highest α-amylase inhibitory activities among the whole series. In addition to α-amylase inhibitory activity, all compounds also demonstrated significant scavenging activities against DPPH and ABTS radicals, with IC50 values ranging from 12.24 to 57.33 and 13.29-59.09 µM, respectively, as compared to the standard ascorbic acid (IC50 = 15.08 ± 0.03 µM for DPPH; IC50 = 16.09 ± 0.17 µM for ABTS). These findings reveal that the nature and position of the substituents on the phenyl ring(s) are crucial for variation in the activities. The structure-activity relationship (SAR) revealed that the compounds bearing an electron-withdrawing group (EWG) at para substitution possessed the highest activity. In kinetic studies, only the km value was changed, with no observed changes in Vmax, indicating a competitive inhibition. Molecular docking studies revealed important interactions between compounds and the α-amylase active pocket. Further advanced research needs to perform on the identified compounds in order to obtain potential antidiabetic agents.

Sakuranetin ameliorates streptozotocin-induced diabetes in rodents by inhibiting caspase-3 activity, modulating hematological parameters, and suppressing inflammatory cytokines: a molecular docking and dynamics study

Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1β (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at −7.489, −6.381, −6.742, −7.202, and −8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent. Communicated by Ramaswamy H. Sarma

Synthesis, in vitro bio-evaluation and in silico molecular docking studies of thiadiazole-based Schiff base derivatives.

Aim: Recently, thiadiazole-containing drugs have gained greater clinical relevance and are being explored for the development of new antidiabetic, antiurease and antimicrobial agents that targetdrug resistance. Methods & results: The authors disclose the synthesis of N-(5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl)methanimine derivatives starting from 4-(trifluoromethyl)benzoic acid. All of the synthesized derivatives were evaluated for their biological potential in order to investigate the inhibitory activity against antidiabetic, antiurease and antibacterial profiles. Compounds 1, 2 and 9 showed excellent inhibitory activities due to the hydrogen bonding presence of -OH, -F and-CF3 substitutions attached with the phenyl ring. Conclusion: The present study provides potent antidiabetic, antiurease and antimicrobial agents that can be further optimized to discover novel antidiabetic, antiurease drugs.

THERAPEUTIC EFFECT OF MORINGA LEAF DECOCTION TO DECREASE BLOOD SUGAR LEVELS AND HBA1C VALUES OF DIABETICS TYPE II DIABETES MELLITUS AT KARANG PANJANG AMBON HEALTH CENTER

Abstract
 Type 2 Diabetes (T2DM) is the most common type of diabetes and is still become one of the causes of death. One way of managing T2DM is mostly by controlling blood sugar, HbA1c levels, developing a healthy diet and herbal alternative therapies. One intervention that does not require expensive costs can be done to improve treatment outcomes in patients with T2DM by controlling blood glucose levels and HbA1c is through moringa leaf decoction therapy. Moringa oleifera (Moringa oleifera) contains and benefits from moringa leaves which have high nutritional value, are rich in minerals, vitamins, and other important phytochemicals. Extracts from the leaves are used to treat malnutrition, as a potential antioxidant, anticancer, anti-inflammatory, antidiabetic and antimicrobial agents.
 This study aims to analyze the therapeutic effect of moringa leaf decoction to decrease blood sugar and HbA1C levels of Type II diabetes mellitus patients in Karang Panjang Ambon Health Center. Sampling technique using consecutive sampling in one intervention group. The study was conducted for seven days with the number of subjects involved in this study as many as 27 people who were measured blood sugar levels and HbA1C before and after treatment.
 This study is a type of quantitative research using pre-experimental approach one group pre-post design. The results of the study obtained the value of SIG 0.000 < 0.050 this states that there is a significant effect of moringa leaf decoction therapy to reduce blood sugar levels and HbA1c values in patients DM Type II
 
 Keywords: moringa leaves, diabetes mellitus Type II, blood sugar, HbA1c

QSAR of Oxazinanone Derivatives As 11-Β Hydroxysteroid Dehydrogenase Type 1 Inhibitor A Potent Anti Diabetic Agent

11-β hydroxysteroid dehydrogenase type 1 is a key enzyme accountable for the interconversion of physiologically inert cortisone to active cortisol thus presents an effective target for the development of pharmacologically active anti diabetic agents focused on manage blood glucose levels, improve insulin sensitivity. The 11β-HSD1 facilitates intracellular cortisol construction that have a disease-causing role in type 2 diabetes and the co-morbidities that it causes. Drugs in habiting the enzyme 11 β-HSD1 offers a potential therapy to lessen the type 2 diabetes. Oxazinanone ring has shown activities as antitumor, antihypertensive, antibacterial, anti-inflammatory, antioxidant and many more. Oxazinanone ring have emerged as potent inhibitors of 11β-HSD1 enzyme. QSAR of Oxazinanone derivatives is performed with a goal of elucidating the key characteristics that cause their anti-diabetic action. QSAR is the most widespread method to ligand-based drug design. It is supposed that structures of the molecules are directly proportional with biological activities, and thus, the biological activities can be altered with any structural changes. The process involves computational or mathematical models to find important correlations between a series of structures and functions. Step wise partial least square, multiple linear regressions, and feed forward neural network were used in a QSAR investigation on enzyme (IC50 nM). The developed models were cross confirmed by the ‘‘leave one out’’ method. The model reveals the significance of steric parameter Verloop B1 (Substitution 1) and Total lipole molecular descriptor.Total lipole bear a resemblance to lipophilicity which is a ratio of the capability of molecules to transfer between oily partition and aqueous partition. These descriptors will have an impact on the design and expansion of novel anti-diabetic 11-hydroxysteroid dehydrogenase type 1 inhibitors.

Synthesis, structural characterizations, in vitro biological evaluation and computational investigations of pyrazole derivatives as potential antidiabetic and antioxidant agents

In this study, a two pyrazole derivatives; 2-(5-methyl-1H-pyrazole-3-carbonyl)-N-phenylhydrazine-1-carboxamide (Pyz-1) and 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (Pyz-2) were synthesized and characterized by 13C-NMR, 1H-NMR, FT-IR, and mass spectrometry. A complete molecular structures optimization, electronic and thermodynamic properties of Pyz-1 and Pyz-2 in gas phase and aqueous solution were predicted by using hybrid B3LYP method with the 6-311++G** basis sets. Pyz-1 and Pyz-2 were evaluated in vitro for their anti-diabetic, antioxidant and xanthine oxidase inhibition activities. For anti-diabetic activity, Pyz-1 and Pyz-2 showed a potent α-glucosidase and α-amylase inhibition with IC50 values of 75.62 ± 0.56, 95.85 ± 0.92 and 119.3 ± 0.75, 120.2 ± 0.68 µM, respectively, compared to Acarbose (IC50(α-glucosidase) = 72.58 ± 0.68 µM, IC50(α-amylase) = 115.6 ± 0.574 µM). In xanthine oxidase assay, Pyz-1 and Pyz-2 exhibited remarkable inhibitory ability with IC50 values 24.32 ± 0.78 and 10.75 ± 0.54 µM, respectively. The result of antioxidant activities showed that the title compounds have considerable antioxidant and radical scavenger abilities. In addition, molecular docking simulation was used to determine the binding modes and energies between the title compounds and α-glucosidase and α-amylase enzymes.

Uptake of vanadium and its intracellular metabolism by Coprinellus truncorum mycelial biomass

BackgroundFungi absorb and solubilize a broad spectrum of heavy metals such as vanadium (V), which makes them a main route of its entry into the biosphere. V as vanadate (V5+) is a potential medical agent due to its many metabolic actions such as interaction with phosphates in the cell, and especially its insulin-mimetic activity. Antidiabetic activity of V-enriched fungi has been studied in recent years, but the biological and chemical bases of vanadium action and status in fungi in general are poorly understood, with almost no information on edible fungi. MethodsThis manuscript gives a deeper insight into the interaction of V5+ with Coprinellus truncorum, an edible autochthonous species widely distributed in Europe and North America. Vanadium uptake and accumulation as V5+ was studied by 51V NMR, while the reducing abilities of the mycelium were determined by EPR. 31P NMR was used to determine its effects on the metabolism of phosphate compounds, with particular focus on phosphate sugars identified using HPLC. ResultsVanadate enters the mycelium in monomeric form and shows no immediate detrimental effects on intracellular pH or polyphosphate (PPc) levels, even when applied at physiologically high concentrations (20 mM Na3VO4). Once absorbed, it is partially reduced to less toxic vanadyl (V4+) with notable unreduced portion, which leads to a large increase in phosphorylated sugar levels, especially glucose-1-phosphate (G1P) and fructose-6-phosphate (F6P). ConclusionsPreservation of pH and especially PPc reflects maintenance of the energy status of the mycelium, i.e., its tolerance to high V5+ concentrations. Rise in G1P and F6P levels implies that the main targets of V5+ are most likely phosphoglucomutase and phosphoglucokinase(s), enzymes involved in early stages of G6P transformation in glycolysis and glycogen metabolism. This study recommends C. truncorum for further investigation as a potential antidiabetic agent.

Polyphenol-Standardized Aphanamixis polystachya Leaf Extract Ameliorates Diabetes, Oxidative Stress, Inflammation, and Fibrosis in Streptozotocin-Induced Diabetic Rats

Background. Diabetes is a rising disorder that affects millions of people annually. It also creates more complications, such as neuropathy, oxidative stress, and hepatic and kidney impairment. Aphanamixis polystachya plant, which possesses multiple medicinal values, is used in this study to explore its potential in treating diabetes. Methods. A single dose (65 mg/kg) of intraperitoneal streptozotocin injection was utilized to mediate diabetes in Sprague-Dawley rats. Diabetic animals were treated orally with 250 or 500 mg/kg of standardized leaves’ extract of A. polystachya (AP) for 28 days to evaluate the antidiabetic and organ-protective effects of the plant. Different biochemical and histological markers are measured according to the established protocol. Results. Our results demonstrated a significant decrease in blood glucose (p <0.001) and HbA1c (p <0.05) levels in the diabetic animal after administering AP (250 and 500 mg/kg doses) compared to the control groups. AP can also regularize lipids, glycogen, alanine aminotransferase, and aspartate aminotransferase. Furthermore, serum urea nitrogen and creatinine decreased after treatment with AP in diabetic rats. AP also reduced oxidative stress markers and showed a substantial elevation in antioxidant enzymes in diabetic animals. Overall, AP at 500 mg/kg revealed comparable results against the standard antidiabetic drug glyburide. Besides, the histological investigation showed the AP’s efficacy in attenuating kidney tissue inflammation and damage. HPLC data elucidated that the AP leaf extract contains polyphenols with potential antioxidant, antidiabetic, and organ protective agents: gallic acid, rutin hydrate, and quercetin hydrate. Conclusion. Taken together, AP may be one of the potential sources of antidiabetic agents.

Synthesis, in vitro enzyme kinetics and molecular docking studies of the 2-formylphenyl sulfonates and their hydrazone derivatives as potential anti-diabetic and anti-inflammatory agents

The in vitro anti-diabetes and anti-inflammatory inhibitory activities of the synthesized 2-formylphenyl sulfonates and their hydrazone derivatives were evaluated through enzymatic assays as potential α-glucosidase and lipoxygenase (LOX-15) inhibitors. The preliminary inhibitory results obtained, revealed that the prepared compounds are good inhibitors of α-glucosidase as compared to lipoxygenase (LOX-15). Compounds 2 g and 3 h were found to exhibit significant inhibitory activities against α-glucosidase with IC50 values of 3.1 µM and 2.6 µM, respectively. Moderate inhibitory activity was also observed for compound 3a (IC50 = 7.3 µM) against this enzyme. Enzyme kinetics studies of the most active compound (3 h) suggested a mixed mode of inhibition for this compound against α-glucosidase. The molecular docking and molecular dynamics simulation of compounds 2 g, 3a and 3 h into the active sites of α-glucosidase were used to predict the binding modes and structure activity relationship for these compounds. The molecular dynamics simulation demonstrated that compound 3 h significant inhibitory activity is due to its ability to bind to both the catalytic and secondary sites of the enzyme.