High-Efficiency Screening of Pancreatic Lipase Inhibitors from Rheum palmatum Using Fe3O4@SiO2@PPL and Mechanistic Investigation of Anti-Obesity Activity
This study establishes an integrated strategy for rapid screening of pancreatic lipase (PPL) inhibitors from Rheum palmatum and elucidates their anti-obesity mechanisms. Fe3O4@SiO2@PPL magnetic nanoparticles were synthesized via chemical co-precipitation, Stöber method, and cross-linking, and characterized by FTIR, SEM, and XRD. Ligand fishing from a 30% ethanol extract specifically captured four compounds: chrysophanol-8-O-β-D-glucopyranoside, aloe-emodin, rhein, and chrysophanol. In vitro enzyme assays confirmed that chrysophanol and aloe-emodin exhibited potent PPL inhibition with IC50 values of 67.03 and 85.86 µmol/L, respectively. Molecular docking revealed that these active components form hydrogen bonds and hydrophobic interactions with key amino acid residues of PPL, consistent with experimental inhibition. Network pharmacology identified 150 overlapping targets between the active compounds and obesity, with five core targets: EGFR, AKT1, SRC, HSP90AA1, and BCL2. Pathway enrichment analysis highlighted the HIF-1 signaling pathway and lipid and atherosclerosis pathway as principal mechanisms. The developed 'material screening–computational validation–network prediction' platform offers a robust tool for high-throughput discovery of natural PPL inhibitors and provides methodological reference for multi-target mechanistic studies of traditional Chinese medicine.