High-Efficiency Screening of Pancreatic Lipase Inhibitors from Rheum palmatum Using Fe3O4@SiO2@PPL and Mechanistic Investigation of Anti-Obesity Activity

• • Chrysophanol and aloe-emodin inhibited pancreatic lipase with IC50 values of 67.03 and 85.86 µmol/L, respectively, demonstrating superior potency compared to rhein and chrysophanol-8-O-β-D-glucopyranoside; these values indicate potential for clinical translation as anti-obesity agents, though further optimization is needed to reach nanomolar efficacy. • • The Fe3O4@SiO2@PPL magnetic nanomaterial enabled specific capture of four ligands from a complex 30% ethanol extract of Rheum palmatum, with FTIR confirming successful enzyme immobilization via Fe-O, Si-O-Si, and -NH2 characteristic peaks; this platform reduces screening time and increases hit specificity compared to conventional colorimetric assays. • • Network pharmacology identified 150 overlapping targets between the active compounds and obesity, with five core targets (EGFR, AKT1, SRC, HSP90AA1, BCL2) and two key pathways (HIF-1 signaling and lipid/atherosclerosis); these targets suggest that the anti-obesity effect involves modulation of cell proliferation, apoptosis, and lipid metabolism, providing a multi-target rationale that single-target inhibitors cannot achieve. • • Molecular docking confirmed that chrysophanol and aloe-emodin bind to pancreatic lipase with higher affinity than rhein and chrysophanol-8-O-β-D-glucopyranoside, forming hydrogen bonds and hydrophobic interactions with key residues; this computational validation aligns with in vitro IC50 data, establishing a reliable predictive framework for screening other natural product libraries.