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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-08, Vol.27 (15), p.4980
• Main Authors: Kausar, Mohd Adnan, Anwar, Sadaf, Eltayb, Wafa Ali, Kuddus, Mohammed, Khatoon, Fahmida, El-Arabey, Amr Ahmed, Khalifa, Amany Mohammed, Rizvi, Moattar Raza, Najm, Mohammad Zeeshan, Thakur, Lovnish, Kar, Subhabrata, Abdalla, Mohnad
• Format: Article
• Language: English
• Subjects: Amylin; Bioactive compounds; Blood pressure; Cholesterol; Complications; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetic nephropathies; Diabetic nephropathy; Diabetic retinopathy; Dialysis; Dihydroxybenzoic acid; Disease; Drug therapy; Epidemics; Gentisic acid; Glucagon; Glucose; Health aspects; Herbal medicine; Homeostasis; Hyperglycemia; Hypoglycemic agents; In vivo methods and tests; in-silico study; Insulin resistance; Kidney transplantation; Kidneys; Kinases; Ligands; MicroRNAs; Molecular docking; Molecular dynamics; molecular dynamics simulation; Nephropathy; Patients; Peptidase; Peptidases; Peptides; Pharmaceutical research; Phytochemicals; Proteins; Public health; Simulation; Urine
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27154980

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.