MD Simulation Studies for Selective Phytochemicals as Potential Inhibitors against Major Biological Targets of Diabetic Nephropathy

Abstract

Diabetes is emerging as an epidemic and is becoming a public health concern worldwide. Diabetic nephropathy is one of the serious complications of diabetes, and about 40% of individuals with diabetes develop diabetic nephropathy. The consistent feature of diabetes and its associated nephropathy is hyperglycemia, and in some cases, hyperamylinemia. Currently, the treatment includes the use of medication for blood pressure control, sugar control, and cholesterol control, and in the later stage requires dialysis and kidney transplantation, making the management of this complication very difficult. Bioactive compounds, herbal medicines, and extracts are extensively used in the treatment and prevention of several diseases, and some are reported to be efficacious in diabetes too. Therefore, in this study, we tried to identify the therapeutic potential of phytochemicals used in in silico docking and molecular dynamic simulation studies using a library of 5284 phytochemicals against the two potential targets of type 2 diabetes-associated nephropathy. We identified two phytochemicals (i.e., gentisic acid and michelalbine) that target human amylin peptide and dipeptidyl peptidase-4, respectively, with good binding affinity. These phytochemicals can be further evaluated using in vitro and in vivo studies for their anti-hyperglycemia and anti-hyperamylinemia effects.

Effectiveness and Safety of Fufang Danshen Dripping Pill (Cardiotonic Pill) on Blood Viscosity and Hemorheological Factors for Cardiovascular Event Prevention in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis

“…anisms [88]. In particular, as confirmed in this study, CDDP reduces the levels of homocysteine and plasma adiponectin.…”

“…As such, CDDP is expected to improve blood viscosity by reducing oxidative stress, increasing microcirculation, protecting blood vessels, and anti-inflammatory and anti-apoptotic effects [23,78]. Research on natural-based candidate substances for the treatment of diabetes complications is also conducted in silico, so future in-silico-based studies on the constituents of CDDP may aid in understanding their mechanisms [88]. In particular, as confirmed in this study, CDDP reduces the levels of homocysteine and plasma adiponectin.…”

GC-MS Based Metabolite Profiling, and Anti-Inflammatory Activity of Aqueous Extract of Myrica esculenta through In Vitro and In Silico Approach

“…During the 100 ns MD simulation, 1000 frames were generated and recorded to the trajectory. Following the MD simulation, the interaction picture was utilized to examine the trajectory of the simulation using RMSD, RMSF, hydrogen bond analysis, and radiation of gyration (rg) [38][39][40].…”

A Study of the Chemical Composition and Biological Activity of Michelia macclurei Dandy Heartwood: New Sources of Natural Antioxidants, Enzyme Inhibitors and Bacterial Inhibitors

“…The lower inhibitory effect of the crude extracts than the alkaloid fraction can be explained by complex interactions (synergistic or antagonistic) among phytochemicals. binding affinity for potential targets for the treatment of diabetes, namely human amylin peptide and dipeptidyl peptidase-4, and can effectively control blood glucose [47]. In addition, magnoflorine, anonaine, apomorphine, and roemerine also have significant efficacy in insulin resistance and obesity suppression [30,48].…”