Evaluation of wound healing active principles in the transdermal patch formulated with crude bio wastes and plant extracts against GSK-3 beta - an in silico study

The wound-healing process is accelerated by inhibiting proteins that decelerate the wound-healing pathway. One of the active proteins involved in enhancing healing at the nuclear level and in gene expression is catenin. Inhibition of Glycogen Synthase Kinase 3β (GSK3 β) phosphorylates and degrades catenin via the downstream Wnt signalling pathway, thereby stabilizing catenin. A medicated wound dressing transdermal patch designed with fusion of bio wastes, viz. physiologically clotted fibrin, fish scale collagen, and the ethanolic extract of Mangifera indica (L.) and spider web, was analysed against GSK3β to enhance healing. In our earlier studies, the compounds present in the transdermal patch were identified using GC-MS analysis; 12 compounds exhibiting the wound healing mechanism were analyzed using PASS software and filtered out. From these 12 compounds, 6 compounds that possessed drug-likeness were screened by SwissADME and vNN-ADMET to dock against GSK3β in the present work. The PyRx results confirmed the binding of the six ligands to the active site of the target protein. Though the remaining filtered ligands also exhibited inhibitory activity, Molecular dynamics simulation studies were carried out with 100 ns on a complex of 10,12 Tricosadiyonic acid, Nopyl acetate and 2 Methyl 4 Heptanol as they showed binding affinity of -6.2Kcal/mol, -5.7Kcal/mol and -5.1Kcal/mol respectively. The stability of the complex was validated using MD simulation parameters RMSD, RMSF, Rg, and Number of Hydrogen bonds. These results implied that the transdermal patch would be efficient in accelerating the wound healing process through the inactivation of GSK3β.Communicated by Ramaswamy H. Sarma.