目的 建立一种集成化研究策略，以实现从掌叶大黄Rheum palmatum中快速筛选胰脂肪酶抑制剂并系统探究其抗肥胖作用机制。方法 采用化学共沉淀法、Stöber法及交联法制备胰脂肪酶修饰磁性纳米材料（Fe₃O₄@SiO₂@PPL），并利用傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）、扫描电子显微镜（scanning electron microscopy，SEM）及X射线衍射（X-ray diffraction，XRD）进行表征；Fe₃O₄@SiO₂@PPL对掌叶大黄提取液进行配体垂钓，利用UPLC及对照品进行初步鉴定；进一步整合分子对接与网络药理学方法，从分子互作、靶点映射及通路富集多个维度进行机制预测。结果 表征结果显示其表面存在酶包覆层及Fe-O、Si-O-Si、-NH₂特征吸收峰，表明胰脂肪酶被成功固载于载体表面。垂钓实验特异性捕获4种化合物，分别为大黄酚-8-O-β-D-葡萄糖苷、芦荟大黄素、大黄酸、大黄酚；其中大黄酚、芦荟大黄素对胰脂肪酶具有较高的抑制作用，其半数抑制浓度（median inhibition concentration，IC₅₀）值分别为67.03、85.86μmol/L。分子对接提示活性成分可与胰脂肪酶关键氨基酸残基形成氢键及疏水相互作用。网络药理学获得活性成分与肥胖交集靶点150个；筛选出表皮生长因子受体（epidermal growth factor receptor，EGFR）、蛋白激酶B1（protein kinase B1，AKT1）、原癌基因酪氨酸蛋白激酶Src（proto-oncogene tyrosine-protein kinase Src，SRC）、热休克蛋白90AA1（heat shock protein 90 alpha family class A member 1，HSP90AA1）、B淋巴细胞瘤-2（B-cell lymphoma-2，BCL2）5个核心靶点；通路富集分析显示HIF-1信号通路和脂质与动脉粥样硬化通路是主要作用途径。结论 开发了一套“材料筛选-计算验证-网络预测”的集成方法，不仅为中药活性成分的高通量发现提供了有效工具，也为从系统生物学角度阐明中药多靶点作用机制提供了方法学参考。

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.

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甘肃省科技计划项目（科技专员专项）（25CXGA022）；甘肃省中药药理与毒理学重点实验室开放课题（ZDSYS-KJ-2024-001）；甘肃中医药大学研究生创新创业基金项目（2026CXCY-320）