In silico investigation of human GLP-1 for diabetic nephropathy and in-vitro and in-vivo evaluation of its...

The prime goal of this work is to evaluate therapeutic potential of interaction between human GLP-1 (HuGLP-1) and Receptor for Advanced Glycation Endproduct (RAGE) interaction by in silico study, followed by investigation of HuGLP-1 loaded liposomes for therapeutics of diabetic nephropathy. The in-silico findings depicted three different docking scores of -134, -1031, and - 306.416 kcal/mol, for the HuGLP-1-RAGE complex from CABS-DOCK, ClusPro, and Schrodinger (Maestro) rigid docking platforms. The ClusPro complex, which exhibited a higher binding energy, was subjected to GROMACS simulations, which verified its stability through a variety of metrics. Further, HuGLP-1 liposomes were formulated. In-vitro studies on DN-induced Human Renal Proximal Tubule Epithelial Cells (hRPTEC) demonstrated that HuGLP-1 liposomes exhibited potent RAGE inhibitory activity and provided significant renal protection. The in-vivo results were also found to be promising enough to establish HuGLP-1 liposomes as a novel therapeutic strategy for diabetic nephropathy.