Drug candidates and potential targets of spp. compounds for treating diabetes mellitus based on network pharmacology, molecular docking and molecular dynamics simulation.

spp. is a herb that is commonly used in Indonesia to treat diabetes mellitus (DM) . The main active components of spp. were identified through our previous metabolomic study and online database platform. However, the biological mechanisms underlying spp. activity in treating DM remain unclear. Therefore, in this study, a network pharmacology was used to explore the active compounds of spp. and their potential molecular mechanisms for treating DM. Oral bioavailability and drug-likeness from the compounds of spp. were screened using Lipinski's rule of five, BBB, HIA + and Caco-2 permeability criteria. A network of compound-target-disease-pathway was then constructed using Cytoscape. The highest degree compounds and targets were then confirmed by molecular docking and molecular dynamics (MD) simulations. The human body can absorb 33 compounds derived from spp. In addition, 58 nodes and 62 edges generated a network analysis with the DM target. The highest degree of the compound-target-disease pathway was for orcinol glucoside, AKR1B1, autoimmune diabetes, bile acid and bile salt metabolism. Furthermore, the computational docking method on spp. compounds with the highest degree revealed that orcinol glucoside interacted with PTPN1 through a hydrogen bond and resulted in a binding energy of -7.2 kcal mol. Through hydrogen bonds, orcinol glucoside in PTPN1 regulates multiple signaling pathways via the adherens junction pathway, which may play a therapeutic role in DM (type 2 diabetes: obesity). In addition, MD simulation confirmed that orcinol glucoside, is suitable for DM treatment by interacting with PTPN1.Communicated by Ramaswamy H. Sarma.