Evaluation of binding interaction between compounds targeting peroxisome proliferator-activated receptor γ in Nelumbinis folium using receptor chromatography and molecular dynamic simulation

Despite considerable efforts invested in clinical trials aimed at treating obesity and enhancing the metabolic profiles of Nelumbinis Folium , the precise phytochemicals involved and their mechanisms of action remain unclear due to the absence of an efficient screening technique. Herein, Nelumbinis Folium serves as the focal point to elucidate the bioactive compounds that specifically bind to peroxisome proliferator-activated receptor γ using immobilized receptor chromatography. Following identification through liquid chromatography-mass spectrometry, the compounds were further evaluated using chromatographic techniques and molecular dynamics simulations. The results unveiled catechin and hypericin as the receptor-binding compounds present in Nelumbinis Folium , with hypericin exhibiting a stronger affinity and a faster dissociation rate constant compared to catechin. Molecular dynamics studies highlighted the crucial role of cysteine located at position of 285 in the receptor ligand binding domain during the initial ligand capture phase. Subsequently, Van Der Waals forces and electrostatic interactions facilitated the binding process. The calculated standard binding free energies were − 61.75 ± 2.61 kcal/mol for hypericin and − 43.19 ± 0.63 kcal/mol for catechin. Collectively, these findings provide valuable insights into receptor-drug interactions and confirm the effectiveness of immobilized receptor chromatography in screening potential lead compounds from complex systems.