Molecular docking, ADMET, and drug-likeness analysis of Garcinia mangostana and Orthosiphon stamineus compounds as drug candidates for metabolic syndrome

Metabolic syndrome comprises metabolic disorders arising from dysfunctional adipose tissue associated with insulin resistance. In recent decades, the incidence of metabolic syndrome has risen significantly alongside the increasing prevalence of global obesity. This study aims to analyze the interactions of phytochemical compounds from Garcinia mangostana and Orthosiphon stamineus and their effects on adiponectin and visfatin activities through PPARγ and AMPK activation, using molecular docking with ADMET profiles and drug-likeness features. Phytochemical compounds were obtained using a UPLC-QToF-MS/MS instrument and then subjected to molecular docking simulations. ADMET profiles and drug-likeness features were predicted using the SwissADME and ProTox-II servers. Docking simulations of sixteen ligand samples identified seven compounds with the most negative binding affinities across the four protein targets. All selected ligand samples are predicted to be absorbed by the gastrointestinal system with good oral bioavailability. Phytochemical compounds from Garcinia mangostana and Orthosiphon stamineus—BR-xanthone B, cyclokievitone, dihydro-O-methylsterigmatocystin, garcimangosone B, 3-hydroxy-3',4',5,7-tetramethoxyflavone, salvigenin, and tangeretin—show good affinity for adiponectin, visfatin, PPARγ, and AMPK compared with other compounds. These interactions may increase insulin sensitivity. All selected ligand samples can be categorized as drug-like molecules and show no predicted hepatotoxicity or cytotoxicity. However, further research is still needed.