scholarly journals Molecular Docking of Compounds in Moringa oleifera Lam with Dipeptidyl Peptidase-4 Receptors as Antidiabetic Candidates

2021 ◽  
Vol 8 (3) ◽  
pp. 242
Author(s):  
Indah Permata Rendi ◽  
Gabriella Josephine Maranata ◽  
Hasna Chaerunisa ◽  
Nurulita Nugrahaeni ◽  
Siti Sarah Alfathonah
Keyword(s):  
Diabetes Mellitus ◽  
Free Energy ◽  
Molecular Docking ◽  
Moringa Oleifera ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp Iv ◽  
Dm Type 2 ◽  
Moringa Oleifera Lam

Background: Diabetes mellitus (DM) type 2 is a metabolic disorder that needs special attention because it can damage several organs if the severity increases. One of the treatments for diabetes mellitus (DM) type 2 is by inhibiting Dipeptidyl peptidase 4 (DPP-IV) with vildagliptin to prolong the hypoglycemic effect of GLP-1 and GIP. Objective: In the search for candidate compounds as new antidiabetic compounds, an in silico test with molecular docking was carried out to predict the antidiabetic activity of 10 Moringa oleifera Lam (MO) plant compounds at the DPP-IV receptor (PDB ID: 6B1E). Method: The study was conducted using the molecular docking method. Result: Validation of the vildagliptin DPP-IV ligand obtained free energy values of -9.27 kcal/mol and RMSD 1.49 Å (RMSD < 2 Å), then tested with 10 test compounds obtained 8 test compounds that have the potential to be antidiabetic. Conclusion: Serpentine compounds have better potential as an antidiabetic drug than other target compounds because they have the closest Gibbs energy (∆G) value to the natural ligand of Vidaglibtin, which is -7.90 kcal/mol. This value is still lower than the free energy of vildagliptin, which is -9.37 kcal/mol. Therefore further testing is needed to ensure the potential of the compound as a candidate for antidiabetic drugs.

scholarly journals Study the effect of Dipeptidyl Peptidase 4 Inhibitors as an Antidiabetic in Type 2 Diabetes Mellitus (T2DM)

2021 ◽  
Vol 11 (5) ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp Iv ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Dipeptidyl peptidase IV is a key regulator of insulin- stimulating hormones, glucagon-like peptide and glucose dependent insulinotrophic polypeptide. Thus it is a promising target for treatment of type 2 Diabetes mellitus. Inhibition of plasma Dipeptidyl peptidase IV enzyme lead to enhanced endogenous glucagon like peptide-1, GIP activity which ultimately results in the potentiating of insulin secretion by pancreatic cell and subsequent lowering blood glucose level, HbA [1c], glucose secretion, liver glucose production. One of the principal goals of diabetes management is to attain haemoglobin HbA [1c] treatment goals and prevent the onset or decrease the rate of occurrence of Microvascular conditions.2, 6 numerous treatment options are available for management of Type 2 Diabetes mellitus, various class of DPP IV inhibitor being explored such as Sitagliptin and Vildagliptin successfully launched. Several other novel DPP IV inhibitors are in pipeline, Unless there are clear contraindications, metformin monotherapy is prescribed, and if HbA [1c] targets are not attained after 3 months, 1 of several classes of agents could be added, such as sulfonylurea’s, Thiazolidinediones, dipeptidyl peptidase-4 inhibitors, - glucagon like peptide-1 receptor agonists, or basal insulin.2,6 Despite the broad range of therapeutic options, the attainment of HbA [1c] goals among patients with diabetes remains challenging, with just slightly more than half (52%) of diabetes patients attaining the common HbA [1c] goal of < 7.0%. The present review summarizes latest preclinical and clinical trial data of different DPP IV inhibitors with a special emphasis on their DPP8/9 fold selectivity and therapeutic advantages over GLP-1 based approach. Keywords: Diabetes 2, Dipeptidyl Peptidase-4, glucose-dependent insulinot

scholarly journals Risk of morbidity and mortality in patients with type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor and/or dipeptidyl peptidase-4 inhibitor: a nationwide study

2021 ◽  
Vol 9 (1) ◽  
pp. e001765
Author(s):  
Gábor Sütő ◽  
Gergő A Molnár ◽  
Gyorgy Rokszin ◽  
Ibolya Fábián ◽  
Zoltan Kiss ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Sodium Glucose Cotransporter ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
All Cause Mortality

IntroductionMortality and disability in diabetes mellitus are determined mostly by cardiovascular complications and cancer. The impact of dipeptidyl peptidase-4 inhibitor (DPP-4i) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) monotherapy or combination on long-term complications of type 2 diabetes mellitus was studied.Research design and methodsPatients with type 2 diabetes treated with DPP-4i or SGLT2i during a 3-year period were identified in the database of the National Institute of Health Insurance Fund in Hungary. All-cause mortality, acute myocardial infarction, stroke, hospitalization for heart failure (HHF), lower limb amputation (LLA) and cancer were assessed. Outcomes of add-on SGLT2i to DPP-4i treatment in comparison with switching DPP-4i therapy to SGLT2i were also evaluated. After propensity score matching, survival analysis was performed with a Cox proportional hazards model.ResultsAfter propensity score matching, both SGLT2i and DPP-4i groups included 18 583 patients. All-cause mortality (HR, 0.80; 95% CI 0.68 to 0.94; p=0.0057), HHF (HR, 0.81; 95% CI 0.71 to 0.92; p=0.0018), and risk of cancer (HR, 0.75; 95% CI 0.66 to 0.86; p<0.0001) were lower in the SGLT2i population compared with DPP-4i. Risk of LLA was higher in the SGLT2i group (HR, 1.35; 95% CI 1.03 to 1.77; p=0.0315). SGLT2i in combination with DPP-4i results in lower all-cause mortality (HR, 0.46; 95% CI 0.31 to 0.67; p=0.0001), with a lower trend in stroke, LLA, HHF and cancer, but without any statistical difference.ConclusionsSGLT2i treatment leads to a lower risk of overall mortality, HHF and cancer when compared with DPP-4i treatment. Adding SGLT2i to DPP-4i instead of switching from DPP-4i to SGLT2i further lowers the risk of all-cause mortality.

scholarly journals Effect of Dipeptidyl-Peptidase 4 Inhibitors on Circulating Oxidative Stress Biomarkers in Patients with Type 2 Diabetes Mellitus

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 233
Author(s):  
Elisabetta Bigagli ◽  
Cristina Luceri ◽  
Ilaria Dicembrini ◽  
Lorenzo Tatti ◽  
Francesca Scavone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Propensity Score ◽  
Oxidative Damage ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors

Pre-clinical studies suggested potential cardiovascular benefits of dipeptidyl peptidase-4 inhibitors (DPP4i), however, clinical trials showed neither beneficial nor detrimental effects in patients with type 2 diabetes mellitus (T2DM). We examined the effects of DPP4i on several circulating oxidative stress markers in a cohort of 32 T2DM patients (21 males and 11 post-menopausal females), who were already on routine antidiabetic treatment. Propensity score matching was used to adjust demographic and clinical characteristics between patients who received and who did not receive DPP4i. Whole-blood reactive oxygen species (ROS), plasma advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), carbonyl residues, as well as ferric reducing ability of plasma (FRAP) and leukocyte DNA oxidative damage (Fpg sites), were evaluated. With the exception of Fpg sites, that showed a borderline increase in DPP4i users compared to non-users (p = 0.0507), none of the biomarkers measured was affected by DPP4i treatment. An inverse correlation between estimated glomerular filtration rate and AGEs (p < 0.0001) and Fpg sites (p < 0.05) was also observed. This study does not show any major effect of DPP4i on oxidative stress, assessed by several circulating biomarkers of oxidative damage, in propensity score-matched cohorts of T2DM patients.

scholarly journals Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 189 ◽  
Author(s):  
Yang Yang ◽  
Chong-Yin Shi ◽  
Jing Xie ◽  
Jia-He Dai ◽  
Shui-Lian He ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Moringa Oleifera ◽  
Molecular Mechanisms ◽  
Dipeptidyl Peptidase ◽  
In Vivo Evaluation ◽  
Docking Analysis ◽  
Dpp Iv ◽  
Molecular Docking Analysis

Moringa oleifera Lam. (MO) is called the “Miracle Tree” because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound 1) had the highest activity (half-maximal inhibitory concentration [IC50] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.

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