目的 基于UPLC-Q-TOF-MS/MS结合网络药理学探讨银翘散抗流感病毒的药效物质基础及潜在作用机制。方法 基于性味理论，研究将银翘散拆方为辛味组（金银花、桔梗、薄荷、牛蒡子、荆芥、生甘草）与苦味组（连翘、淡豆豉、淡竹叶、生甘草），并通过观察银翘散及其拆方对流感风热证小鼠的保护作用，结合血清药物化学及网络药理学方法评价银翘散及其拆方抗流感的有效活性成分，探究其抗流感病毒的“味-效”物质基础，预测其可能的作用机制。结果 银翘散及其拆方对流感风热证小鼠均具有一定的保护作用。其中，在维持小鼠体质量及降低肺指数方面，辛味组较苦味组改善效果更优；苦味组在维持大便湿质量、降低中性粒细胞百分比、升高淋巴细胞比例方面，效果优于辛味组。总体来看，银翘散在各方面改善效果最为显著。基于UPLC-Q-TOF-MS/MS技术鉴定出银翘散中725个化学成分、73个入血成分，辛味组中617个化学成分、53个入血成分，苦味组中595个化学成分、47个入血成分。网络药理学显示，银翘散及其拆方中35个共同靶点（TP53、STAT3等）通过调控病毒生命周期（介导病毒内化、参与病毒复制等）与宿主防御（免疫反应、炎症反应等），构成抗流感病毒的共性作用基础。辛味组对Th17细胞分化与人体免疫缺陷病毒1感染通路的特异性激活，苦味组对病灶黏附、细胞凋亡与TNF信号通路的显著干预，可能是其发挥“辛味”与“苦味”功效的分子机制。结论 该研究揭示银翘散及其拆方的药效学物质基础，预测其潜在的抗病毒作用可能与炎症反应、免疫反应等相关信号通路有关，为银翘散的临床应用提供理论依据。

Objective To explore the pharmacodynamic substance basis and potential mechanisms of action of Yinqiao Powder against influenza virus based on UPLC-Q-TOF-MS/MS combined with network pharmacology. Methods Based on the theory of properties and flavors, this study divided Yinqiao Powder into the pungent flavor group（Lonicerae Japonicae Flos, Platycodonis Radix, Menthae Haplocalycis Herba, Arctii Fructus, Schizonepeta tenuifolia, Glycyrrhizae Radix et Rhizoma） and the bitter flavor group（Forsythiae Fructus, Sojae Semen Praeparatum, Lophatherum gracile, Glycyrrhizae Radix et Rhizoma）. By observing the protective effects of Yinqiao Powder and its divided formulas on mice with influenza of wind-heat syndrome, combined with the methods of serum pharmacochemistry and network pharmacology, the effective active components of Yinqiao Powder and its divided formulas against influenza were evaluated, the “flavor-effect” material basis of their anti-influenza virus effects was explored, and their possible mechanisms of action were predicted. Results The results showed that Yinqiao Powder and its divided formulas all had certain protective effects on mice with influenza of wind-heat syndrome. Among them, in terms of maintaining the body weight of mice and reducing the lung index, the pungent flavor group had a better improvement effect than the bitter flavor group; the bitter flavor group was superior to the pungent flavor group in maintaining the wet weight of feces, reducing the percentage of neutrophils, and increasing the proportion of lymphocytes. Overall, Yinqiao Powder had the most significant improvement effect in all aspects. Based on the UPLC-Q-TOF-MS/MS technology, 725 chemical components and 73 blood components were identified in Yinqiao Powder, 617 chemical components and 53 blood components in the pungent flavor group, and 595 chemical components and 47 blood components in the bitter flavor group. Network pharmacology showed that 35 common targets（such as TP53 and STAT3） in Yinqiao Powder and its divided formulas regulated the virus life cycle（mediating virus internalization, participating in virus replication, etc.） and host defense（immune response, inflammatory response, etc.）, forming a common basis for their anti-influenza virus effects. The specific activation of the Th17 cell differentiation and human immunodeficiency virus 1 infection pathways by the pungent flavor group, and the significant intervention of the bitter flavor group in lesion adhesion, apoptosis, and the TNF signaling pathway may be the molecular mechanisms for the exertion of their "pungent flavor" and "bitter flavor" effects. Conclusion This study revealed the pharmacodynamic material basis of Yinqiao Powder and its divided formulas, predicted that their potential antiviral effects may be related to related signaling pathways such as inflammatory response and immune response, and the results can provide a theoretical basis for the clinical application of Yinqiao Powder.

R285.5

国家自然科学基金资助项目(81803971); 河南省高等学校青年骨干教师培养计划项目(2019GGJS111); 河南省高等学校重点科研项目指导计划项目(18B360009); 河南省“双一流”创建学科中医学科学研究专项(HSRP-DFCTCM-2023-8-45)