Insilco study of the effect of hesperetin on three pre-apoptotic factors Bad, Bak, Bim

Background and Aim Many compounds derived from medicinal plants, such as antioxidants and polyphenols have significant roles in prevention and treatment of various cancers. Activation of apoptosis related pathways is one of the mechanisms for inhibition of cancer progression. In this study, we investigated the effect of molecular dynamics simulation of hesperetin on the pre-apoptotic factors of Bad, Bak, and Bim. Material and Methods In this study we collected data about 3 dimensional structure and Protein Data Bank (PDB) files of three apoptotic factors of Bad, Bak, and Bim from Protein Data Bank (http://www.rscb.org/pdb). Using VMD v1.9.2, AutoDock v.4.2, and Gromacs v.4.5.4 softwares, we started processes such as optimization, simulation, molecular docking and molecular dynamics calculations. Results Binding of Bad molecule to hesperetin led to release of the highest amount of energy and reduced changes in the radius of gyration of Bad protein. But after binding of Bim and Bak proteins to hesperetin, changes in the radius of gyration, increased. The most frequent change in the secondary protein structure was related to increased amount of Bent structure and decreased amount of β-sheet structure in Bim molecule. Conclusion Hesperetin can affect the activities of pre-apoptotic factors of Bad, Bak, and Bim by influencing their molecular dynamics. It seems that hesperetin has the highest effect on the activation of Bad molecule. Also, it can activate Bim protein and induce apoptosis via inducing alternations in the secondary structure of the protein. Keywords: Molecular dynamic , Apoptosis , Hespereti

Evaluating the Effects of Molecular Dynamic And Docking of Abemaciclib, Hymenialdisine, and Indirubin on CDK-2 Inhibition by Simulation Study

Background & objectives: Cyclin-dependent kinase 2 (CDK-2) is a serine/threonine protein kinase with regulatory activity in the cell cycle. Inhibitors of this protein are the treatment of choice for a variety of cancers by stopping the cell cycle. In this in silico study, the effects of docking and molecular dynamics of Abemaciclib, Hymenialdisine, and Indirubin on the inhibition of CDK-2 as one of the most important factors in the cell cycle have been investigated. Methods: PDB file of CDK-2 protein as well as three-dimensional structures of Abemaciclib, Hymenialdisine, and Indirubin were obtained from the protein database (http://www.rcsb.org) and pubchem server, respectively. After simulating CDK-2 in Gromacs software, molecular docking of compounds on CDK-2 was performed by AutoDock 4.2 software. Finally, the most important molecular dynamics factors such as RMSD,the radius of gyration and total energy in the pre-docking state were analyzed and compared to these factors in the post-docking stage. Results: Abemaciclib has the highest affinity for binding to amino acids at the CDK-2 binding site by releasing binding energy equivalent to 8.23 kJ/mol. The binding of Abemaciclib, Hymenialdisine, and Indirubin to CDK-2, resulted in significant reductions in some molecular dynamics factors such as mean total energy, the radius of gyration, RMSD, and changes in CDK-2 secondary structure. Conclusion: Abemaciclib, Hymenialdisine, and Indirubin have a high tendency to interact with CDK-2, and this binding can induce significant dynamic molecular changes in the structure of CDK-2 molecule. Based on the results of molecular dynamics simulation, the secondary structure of CDK-2 changes after each ligand binds to it and makes the complex of ligand and protein more stable. Article number: 4 Keywords: CDK-2, Abemaciclib, Hymenialdisin, Indirubin, Molecular Dynamic Simulatio

The Effect of Metformin on Bad, Bak, and Bim Pro-apoptotic Factors: A Molecular Dynamic Simulation Study

Background: Recent investigations have demonstrated that metformin treatment can decrease tumor incidence and growth using cell cycle arrest and induction of apoptosis pathway. However, it is not clear how metformin affects the factors involved in the apoptotic process. Objective: The present study aimed to determine the effect of metformin on Bak, Bad, and Bim pro-apoptotic proteins using docking and dynamics simulation studies. Methods: The 3D structure of molecules was retrieved from PubChem and RCSB servers. Simulation and docking studies were conducted by Gromacs and AutoDock software. Next, molecular dynamics analysis was performed using Gromacs software. Moreover, LigPlot+V.4.5.3 software was applied for the determination of the hydrogen and hydrophobic interactions at the binding sites. Results: Our findings demonstrated that metformin has the highest affinity for binding the Bak pro-tein. This binding occurred using four amino acid residues within the binding site of Bak with the minimum binding energy (-5.70 kcal/mol). The molecular docking of metformin to these pro-apoptotic factors significantly decreased the total energy and increased the coil secondary structure of Bak protein. Conclusion: According to our findings, metformin can alter the molecular dynamics property of these proteins, which results in increased activity of these pro-apoptotic proteins and induction of apoptosis

The effect of cinnamon supplementation on lipid profiles in patients with type 2 diabetes:A systematic review and meta-analysis of clinical trials

Objective: The present systematic review and meta-analysis was performed to evaluate the effect of cinnamon supplementation on blood lipid profiles in patients with type 2 diabetes. Methods: A systematic search (with no language restrictions) was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library to identify relevant clinical trials up to 8th March 2020. Weighted mean differences (WMDs) and 95 % confidence intervals (CI) were pooled based on the random-effects model. Heterogeneity, publication bias, and sensitivity analyses were performed based on standard methods. Results: Sixteen studies, involving 1025 participants, were included in the meta-analysis. This study found a significant decrease in triglycerides (TG) (WMD: -26.27 mg/dl, 95 % CI: [-38.93, -13.61], P < 0.001), total cholesterol (TC) (WMD: -13.93 mg/dl, 95 % CI: [-25.64, -2.22], P = 0.020), and low-density lipoprotein cholesterol (LDL-C) levels (WMD: -6.13 mg/dl, 95 % CI: [-10.72, -1.53], P = 0.009), while no change was observed on high-density lipoprotein cholesterol (HDL) concentration (WMD: 0.64 mg/dl, 95 % CI: [-0.18, 1.46], P = 0.128), in patients with type 2 diabetes. The reduction in TG, TC, and LDL-C was greater in; Eastern compared to Western countries, and studies with a duration of < 2 compared to ≥ 2 months. The increase in HDL was greater in; participants with a BMI ≥ 30 compared to <30, Western compared to Eastern countries, and intervention durations of ≥ 2 compared to < 2 months. Conclusions: Cinnamon supplementation significantly decreased serum TG, TC, and LDL-C concentrations, but did not change HDL-C levels, in patients with type 2 diabetes