目的 分离小檗余甘子汤中纳米超分子部位，进行理化表征，并探究其改善胰岛素抵抗（insulin resistance，IR）作用及机制。方法 采用离心透析法从小檗余甘子汤煎液中分离纳米超分子部位，以扫描电镜（scanning electron microscope，SEM）进行形态表征，根据丁达尔效应评价稳定性。采用UPLC-Q-Exactive Orbitrap MS技术对纳米超分子进行化学成分分析。以葡萄糖胺为诱导剂建立HepG2细胞IR模型，通过CCK-8法筛选合适的给药浓度。以葡萄糖消耗量为指标评价小檗余甘子汤不同部位对HepG2细胞IR的影响。采用免疫蛋白印记法测定磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）/蛋白激酶B（protein kinase B，AKT）通路相关蛋白的表达。结果 小檗余甘子汤中形成的超分子为性质稳定、均一的球形纳米颗粒，粒径约为514 nm，多分散系数（polydispersity index，PDI）为0.398，Zeta电位为–14.1 mV。纳米超分子主要以小檗碱等生物碱类和没食子酸等多酚类成分组成，具有较好的pH稳定性和离子稳定性。与模型组比较，纳米超分子部位可显著提高葡萄糖消耗量，明显上调p-PI3K/PI3K、p-AKT/AKT蛋白表达，且药效与小檗余甘子汤全汤相当。结论 小檗余甘子汤中存在形态均一、性质稳定的超分子纳米颗粒，是改善胰岛素抵抗的关键药效物质，其作用机制与激活PI3K/AKT信号通路有关。

Objective To isolate the nanosupramolecular parts of Xiaoboyuganzi Decoction, perform physicochemical characterization, and investigate its effects and mechanisms of improving insulin resistance (IR).Methods Nanosupramolecular was isolated from Xiaoboyuganzi Decoction using centrifugal dialysis, morphologically characterized by scanning electron microscopy (SEM), and their stability was evaluated by the Tyndall effect. The chemical composition of the nanosupramolecular was analyzed by UPLC-Q-Exactive Orbitrap MS technique. An IR model was induced in HepG2 cells with glucosamine, and cell viability was assessed by CCK-8 assay. Glucose consumption was used as an indicator to assess the effects of different components of Xiaoboyuganzi Decoction on IR in HepG2 cells. The expression levels of proteins related to the PI3K/AKT pathway were determined using western blotting.Results The supramolecules formed in Xiaoboyuganzi Decoction were stable and homogeneous spherical nanoparticles, with a particle size of approximately 514nm, a polydispersity index (PDI) of 0.398, and a zeta potential of –14.1 mV. The nanosupramolecular was primarily composed of berberine and other alkaloids, as well as gallic acid and other polyphenols, and exhibited good pH stability and ionic stability. Compared with the model group, the nanosupramolecular significantly increased glucose consumption and upregulated the expression of p-PI3K/PI3K and p-AKT/AKT proteins, with efficacy comparable to that of the Xiaoboyuganzi Decoction.Conclusion Supramolecular nanoparticles with uniform morphology and stable properties exist in Xiaoboyuganzi Decoction, which is a key pharmacodynamic substance for improving insulin resistance, and its mechanism is related to the activation of PI3K/AKT signaling pathway.

R284.1

四川省自然科学基金项目（2024NSFSC0691）；四川省重点研发项目（2022YFS0434）