As for ligand fishing, the current immobilization approaches have some potential drawbacks such as the small protein loading capacity and difficult recycle process. The core–shell metal–organic frameworks composite (Fe₃O₄-COOH@UiO-66-NH₂), which exhibited both magnetic characteristics and large specific surface area, was herein fabricated and used as magnetic support for the covalent immobilization of porcine pancreatic lipase (PPL). The resultant composite Fe₃O₄-COOH@UiO-66-NH₂@PPL manifested a high loading capacity (247.8 mg/g) and relative activity recovery (101.5%). In addition, PPL exhibited enhanced tolerance to temperature and pH after immobilization. Then, the composite Fe₃O₄-COOH@UiO-66-NH₂@PPL was incubated with the extract of Scutellaria baicalensis to fish out the ligands. Eight lipase inhibitors were obtained and identified by UPLC-Q-TOF-MS/MS. The feasibility of the method was further confirmed through an in vitro inhibitory assay and molecular docking. The proposed ligand fishing technique based on Fe₃O₄-COOH@UiO-66-NH₂@PPL provided a feasible, selective, and effective platform for discovering enzyme inhibitors from natural products.

Ligand fishing combined with knock-out/knock-in chromatography to efficiently screen components with α-glucosidase inhibitory activities from Pueraria lobata and evaluate holistic activities and interactions between these constituents.

Colorectal cancer (CRC) remains a leading cause of cancer mortality, necessitating novel therapeutic strategies. Schisandrin C (SinC), a bioactive lignan from Schisandra chinensis , exhibits diverse pharmacological activities, but its anti‐CRC mechanisms are poorly understood. This study investigated the anti‐CRC mechanism of SinC, focusing on PPARγ‐mediated ferroptosis and macrophage polarization. Network pharmacology predicted core targets and pathways. Direct SinC‐PPARγ binding was confirmed by molecular docking, CETSA, and luciferase reporter assays. In HCT116 and LoVo cells, proliferation, migration, and ferroptosis were evaluated, with mechanistic validation using a PPARγ agonist, antagonist, and shRNA. M1/M2 markers in RAW264.7 macrophages were detected. In an AOM/DSS‐induced CAC mouse model, ferroptosis and macrophage polarization were assessed by Prussian blue staining, immunohistochemistry, and Western blotting. SinC directly bound and activated PPARγ, concentration‐dependently inhibiting CRC cell proliferation, migration, and colony formation while inducing ferroptosis—effects reversed by liproxstatin. Mechanistically, SinC activated PPARγ, suppressed JAK2/STAT3 signaling, and downregulated SLC7A11/GPX4, effects enhanced by a PPARγ agonist and abolished by PPARγ antagonist or shRNA. SinC upregulated M1 markers and pro‐inflammatory cytokines, with a predominant M1‐associated activation pattern. In CAC model, SinC improved survival, inhibited tumor growth, alleviated colonic pathology, exhibited biochemical features consistent with ferroptosis, and increased intratumoral CD86 ⁺ cell infiltration. SinC directly binds and activates PPARγ transcriptional activity, inducing ferroptosis in CRC cells via the PPARγ‐JAK2/STAT3‐SLC7A11/GPX4 axis while concurrently promoting M1 macrophage polarization, exerting a dual antitumor effect. These findings support SinC as a promising therapeutic candidate for CRC.