中草药2026，Vol.57Issue(15)：5814-5824,11.DOI:10.7501/j.issn.0253-2670.2026.15.004
基于Fe3O4@SiO2@PPL的掌叶大黄胰脂肪酶抑制剂高效筛选及抗肥胖机制研究
High-efficiency screening of pancreatic lipase inhibitors of Rheum palmatum based on Fe3O4@SiO2@PPL and their anti-obesity mechanism study
摘要
Abstract
Objective To develop an integrated strategy for rapid screening of pancreatic lipase(PPL)inhibitors from Rheum palmatum and systematically investigate their potential anti-obesity mechanisms.Methods Fe3O4@SiO2@PPL was synthesized via chemical co-precipitation,Stöber method,and cross-linking,and characterized by Fourier transform infrared spectroscopy(FT-IR),scanning electron microscopy(SEM),and X-ray diffraction(XRD).The Fe3O4@SiO2@PPL was applied in ligand fishing experiments on an ethanol extract of R.palmatum,and the captured ligands were identified by UPLC with reference standards.Molecular docking and network pharmacology were integrated to conduct mechanism prediction from multiple dimensions such as molecular interaction,target mapping,and pathway enrichment.Results Material characterization revealed the presence of an enzyme coating layer on the surface,along with characteristic absorption peaks of Fe-O,Si-O-Si,and-NH2,indicating that pancreatic lipase was successfully immobilized on the carrier surface.Four compounds were specifically captured by fishing experiments,including chrysophanol-8-O-β-D-glucopyranoside,aloe-emodin,rhein,and chrysophanol.Among them,chrysophanol and aloe-emodin exhibited high inhibitory effects against pancreatic lipase,with median inhibition concentration(IC50)values of 67.03 and 85.86 μmol/L,respectively.Molecular docking suggested that the active components can form hydrogen bonds and hydrophobic interactions with key amino acid residues of pancreatic lipase.Network pharmacology identified 150 overlapping targets between the active components and obesity.Screening out the five core targets:epidermal growth factor receptor(EGFR)and protein kinase B1(AKT1),proto-oncogene tyrosine-protein kinase Src(SRC),heat shock protein 90 alpha family class A member 1(HSP90AA1),and B-cell lymphoma-2(BCL2).Pathway enrichment analysis indicated that the HIF-1 signaling pathway and the lipid and atherosclerosis pathway were the main mechanisms of action.Conclusion An integrated approach combining material-based screening,computational validation,and network prediction was established.This strategy provides an efficient tool for high-throughput screening of bioactive compounds from traditional Chinese medicines and offers methodological insights into clarifying the multi-target action mechanism of traditional Chinese medicine from the perspective of systems biology.关键词
抗肥胖/胰脂肪酶抑制剂/掌叶大黄/固定化酶/配体垂钓/网络药理学/分子对接/大黄酚-8-O-β-D-葡萄糖苷/芦荟大黄素/大黄酸/大黄酚Key words
anti-obesity/pancreatic lipase inhibitor/Rheum palmatum L./enzyme immobilization/ligand fishing/network pharmacology/molecular docking/chrysophanol-8-O-β-D-glucopyranoside/aloe-emodi/rhein/chrysophanol分类
医药卫生引用本文复制引用
武晓玉,马银云,陶子豪,迪丽尼尕尔·阿布都艾尼,张欣艺,吴国泰,魏舒畅,段文达,潘燕龙,赵磊..基于Fe3O4@SiO2@PPL的掌叶大黄胰脂肪酶抑制剂高效筛选及抗肥胖机制研究[J].中草药,2026,57(15):5814-5824,11.基金项目
甘肃省科技计划项目(科技专员专项)(25CXGA022) （科技专员专项）
甘肃省中药药理与毒理学重点实验室开放课题(ZDSYS-KJ-2024-001) （ZDSYS-KJ-2024-001）
甘肃中医药大学研究生创新创业基金项目(2026CXCY-320) （2026CXCY-320）
