Hypothesis validation of rosiglitazone a potential inhibitor against glycogen synthase kinase-3β, for the management of multifaceted pathophysiology of the diabetic wound: An insilico study

Abstract

Diabetic wound (DW) is a major complication of diabetes mellitus that often ends up with amputation of the concerned organ. The current therapies for DW include glucose regulation, wound debridement, pressure off-loading, surgeries, hyperbaric oxygen therapy, maggot therapy, and so on. However, the majority are not meeting all the prerequisites of DW because of extensive pathology and cost associated with the strategies. So, to overcome the problems related to the existing conventional therapies, we hypothesized to repurpose the current drugs, which can target a receptor having a considerable role in the progression of DW might be beneficial. One major challenge of DW is multifaceted pathophysiology includes prolonged inflammation, increased infections, decreased cell proliferation, and migration. Many shreds of evidence disclosed that inhibition of GSK-3β could result in reduced inflammation and infection, followed by increased cell proliferation and migration. Thus, we selected the GSK-3β receptor as a ubiquitous target for the treatment of multifactorial pathophysiology of DW. In the current hypothetical study, we investigated the use of rosiglitazone as a therapeutic modulator against the GSK-3β receptor. To validate our hypothesis, computational studies such as molecular docking and MMGBSA were performed. From the in silico methods, it is evident that rosiglitazone established a higher binding affinity against the selected receptor. Further, the Molecular Dynamic simulation study has revealed stable interaction of rosiglitazone against GSK-3β complex. Thus, rosiglitazone might be a drug of choice in the therapeutic management of DW.