目的 基于颜色-特征成分关联分析及网络药理学探讨金银花Lonicerae Japonicae Flos中潜在的质量标志物（quality markers，Q-Marker）。方法 收集山东、河南和河北3个产地共30批金银花样品，建立金银花HPLC特征图谱方法，得到金银花中的非挥发性特征成分，将其与实验室前期得到的含量较高、具有产地特异性的挥发性成分相结合，作为金银花潜在的Q-Marker候选物；采用色彩分析仪测定金银花的颜色与Q-Marker进行相关性分析，筛选出与颜色相关的成分；结合网络药理学方法，从金银花的适应证和功效2个层面对Q-Marker候选物的药理活性进行预测，进一步确定潜在Q-Marker。结果 建立了金银花非挥发性成分HPLC特征图谱，指认了9个特征峰，结合实验室前期对挥发性成分研究结果，最终从金银花中得到了16种特征性成分；相关性分析结果表明，与金银花颜色具有显著相关性的成分有10个，包括绿原酸、当药苷、断氧马钱子苷、芦丁、(Z)-二聚断马钱苷烯醛、异绿原酸B、异绿原酸C、α-亚麻酸甲酯、正己醛、(E, E)-2,4-癸二烯醛；网络药理学研究得到11种与疾病和药效关联的Q-Marker，分别为当药苷、断氧马钱子苷、芦丁、(Z)-二聚断马钱苷烯醛、异绿原酸B、异绿原酸A、芳樟醇、肉豆蔻酸、α-亚麻酸甲酯、α-橙花醇、月桂醛。通路富集分析结果显示，这些成分主要通过丝裂原活化蛋白激酶1（mitogen-activated protein kinase 1，MAPK1）、丝裂原活化蛋白激酶激酶1（recombinant mitogen activated protein kinase kinase 1，MAP2K1）、丝裂原活化蛋白激酶14（mitogen-activated protein kinase 14，MAPK14）、肿瘤坏死因子（tumor necrosis factor，TNF）等62个关键靶点作用于细胞凋亡（apoptosis）、表皮生长因子受体（epidermal growth factor receptor，EGFR）、松弛素（relaxin）、C型凝集素（C-type lectin receptor）、白细胞介素17（interleukin 17，IL-17）、结合免疫球蛋白E的Fc受体（Fc epsilon RI）、T细胞抗原受体（T cell receptor）等多种信号通路。将颜色和药理活性成分取交集，最终得到6种与颜色关联的Q-Marker，包括当药苷、断氧马钱子苷、芦丁、异绿原酸B、(Z)-二聚断马钱苷烯醛、α-亚麻酸甲酯。因此，为提高金银花的质量标准，可以考虑在《中国药典》标准基础上，将芦丁、异绿原酸B、α-亚麻酸甲酯、芳樟醇和肉豆蔻酸纳入金银花的质量评价体系。结论 从理论层面出发，筛选出能够体现其质量的Q-Marker，为全面控制金银花的质量提供依据，为进一步研究金银花的活性物质及其作用机制提供参考。

Objective To screen the potential quality markers (Q-Marker) of Jinyinhua (Lonicerae Japonicae Flos, LJF) based on color-characteristic components association analysis and network pharmacology. Methods A total of 30 batches of LJF were collected from Shandong, Henan and Hebei provinces, and HPLC characteristic chromatogram method based on non-volatile components was established to obtain the characteristic components, which was combined with volatile components with high content and province-specific obtained in previous laboratory, as potential Q-Marker candidate for LJF. The color of LJF was measured by visual analyzer, and correlation analysis was carried out with Q-Marker, and the components with significant correlation with color were obtained. The pharmacologic activities of Q-Marker candidates were predicted by network pharmacological methods, and potential Q-Marker was further screened out based on two aspects of main efficacy and clinical indications of LJF. Results HPLC chromatogram of non-volatile components of LJF was established, and nine characteristic peaks were identified, finally 16 characteristic components were obtained from LJF combined with the previous research results of volatile components. Correlation analysis results showed that 10 components were significantly correlated with the color of LJF, including chlorogenic acid, sweroside, secoxyloganin, rutin, centauroside, isochlorogenic acid B, isochlorogenic acid C, methyl linolenate, hexanal, (2E,4E)-deca-2,4-dienal; Eleven Q-Markers associated with disease and efficacy were obtained through network pharmacological study, which were sweroside, secoxyloganin, rutin, centauroside, Isochlorogenic acid B, isochlorogenic acid A, linalool, myristic acid, methyl linolenate, nerol, lauraldehyde. These components mainly act on apoptosis, epidermal growth factor receptor (EGFR), relaxin, C-type lectin receptor, Interleukin 17 (IL-17), Fc epsilon RI, T cell receptor through 62 key targets, such as mitogen-activated protein kinase 1 (MAPK1), recombinant mitogen activated protein kinase kinase 1 (MAP2K1), mitogen-activated protein kinase 14 (MAPK14), tumor necrosis factor (TNF), and so on. In addition, six Q-Markers associated with color were finally obtained, including sweroside, secoxyloganin, rutin, isochlorogenic acid B, centauroside, methyl linolenate. Therefore, in order to improve the quality standard of LJF, rutin, isochlorogenic acid B, methyl linolenate, linalool and myristic acid could be considered to be included in the quality evaluation system of LJF based on the pharmacopoeia standard. Conclusion From the theoretical level, Q-Markers reflecting the quality of LJF screened by this study can provide a basis for the overall control of the quality of LJF, with view to providing a reference for further research on the active substances of LJF and their mechanism of action

R286.2

国家科技基础性工作专项（2015FY111500）;国家中医药管理局中药炮制技术传承基地项目（国中医药科技中药［2022］59号）;中国中医科学院中药研究所横向课题（H2020113）