Network Pharmacology and Molecular Docking Studies of Ethnopharmacological Plants from Sulawesi as Antidiabetics

Diabetes is a degenerative disease affecting many people in Indonesia, where herbal preparations offer an alternative treatment. This study aims to identify potential antidiabetic drugs from four ethnopharmacological plants of Sulawesi (Cordia myxa L., Syzygium cumini, Syzygium malaccense, and Antidesma bunius) using network pharmacology and molecular docking approaches. Secondary metabolites in the ethanolic extracts were identified using gas chromatography-mass spectrophotometry (GC-MS), followed by analysis of potential antidiabetic targets through network pharmacology and docking studies with Molecular Operating Environment (MOE) software. Network pharmacology revealed PPARG as a potential target for C. myxa and GCG receptors for the other plants. Docking analysis showed that C. myxa compounds bind strongly to PPARG (PDB ID: 5YCP), surpassing Rosiglitazone (-7.49635 kcal/mol), with top binding energies observed for Squalane (-9.6078 kcal/mol), 2,6,10,14,18,22-Tetracosahexaene, 2,6,10,15,19,23-hexamethyl-(all-E)- (-8.7069 kcal/mol), and Anodendroside G monoacetate (-8.0845 kcal/mol). Meanwhile, for GCG (PDB ID: 5EE7) receptor interactions, several compounds demonstrated stronger binding than MK-0893 (-5.66941 kcal/mol). A. bunius exhibited the highest GCG binding affinities from terpenoid of 2,5,7,8-Tetramethyl-2-(4,8,12-Trimethyltridecyl)-3,4-Dihydro-2h-Chromen-6-Yl Hexofuranoside (-8.8001 kcal/mol), while S. malaccense and S. cumini compounds showed moderate to strong binding energies ranging from -7.6398 to -6.5939 kcal/mol. These findings highlight the significant antidiabetic potential of C. myxa targeting PPARG and A. bunius, S.malaccense and S.cumini targeting GCG receptors, offering promising candidates for antidiabetic drug development.