整合文献计量学、血清药物化学及网络药理学辨识经典名方化肝煎关键质量属性研究

Integrated bibliometrics, serum pharmacochemistry and network pharmacological analysis used to preliminarily identify critical quality attributes of classic prescription Huaganjian

目的基于有效性初步辨识化肝煎治疗胃炎的关键质量属性。方法通过文献计量学分析探析化肝煎主要临床适应证;采用UPLC-Q-Exactive Orbitrap-MS技术对化肝煎体外化学成分及体内入血移行成分进行分析鉴定;使用Cytoscape软件,构建化肝煎"入血成分-胃炎靶点-通路"网络图,通过拓扑学分析,得到网络中与主要临床适应证密切相关的核心功效成分。结合文献数据支撑,确定化肝煎的关键质量属性。结果化肝煎临床上主要用于治疗各种类型的胃炎。体外共鉴定出化肝煎中泽泻醇B、贝母辛、圣草次苷、苯甲酰氧化芍药苷等75个成分,体内共检测到16个化肝煎入血原型成分,分别为莽草酸、丹皮酚、芍药苷、牡丹皮苷E、西贝母碱、贝母素甲、贝母素乙、贝母辛、对羟基苯甲酸、香风草苷、香草乙酮、6-去甲氧基桔皮素、甜橙黄酮、川陈皮素、3,5,6,7,8,3,,4’-七甲氧基黄酮、桔皮素。化肝煎治疗胃炎涉及AKT1、TNF、VEGFA、MAPK1、EGFR等95个潜在靶点,可能通过调控C型凝集素受体、PI3K-Akt、白细胞介素-17、肿瘤坏死因子等信号通路发挥治疗作用。甜橙黄酮、3,5,6,7,8,3’,4’-七甲氧基黄酮、川陈皮素、丹皮酚、芍药苷作为化肝煎的关键质量属性。结论辨识的化肝煎关键质量属性可为经典名方复方制剂研发提供依据。

Objective The critical quality attributes of Huaganjian(化肝煎)were preliminarily identified according to efficacy.Methods The principal clinical indications of Huaganjian were analyzed by bibliometrics.UPLC-Q-Exactive Orbitrap-MS was used to identify chemical components of Huaganjian and migrating components absorbed into blood.A network of Huaganjian that involved migrating components,gastritis targets,and signal pathways was constructed.Topological analysis was performed to recognize the core active ingredients closely related to gastritis treatment in the network,combined with relevant literature,critical quality attributes of Huaganjian were confirmed.Results Huaganjian was always used to treat various types of gastritis.A totoal of 75 chemical components of Huaganjian were identified,such as alisol B,peimisine,eriocitrin,benzoyloxypaeoniflorin and so on.Sixteen prototype components,including shikimic acid,paeonol,paeoniflorin,mudanpioside E,imperialine,peimine,peiminine,peimisine,4-hydroxybenzoic acid,didymin,acetovanillone,6-demethoxytangeretin,sinensetin,nobiletin,3,5,6,7,8,3′,4′-heptamethoxyflavone,tangeritin,absorbed into blood were associated with 95 potential targets(AKT1,TNF,VEGFA,MAPK1,EGFR,etc.)of gastritis treatment.Huaganjian may exert therapeutic effects by modulating PI3 K-Akt signaling pathway,C-type lectin receptor signaling pathway,interleukin-17 signaling pathway,and tumor necrosis factor signaling pathway and so on.Sinensetin,3,5,6,7,8,3′,4′-heptamethoxyflavonoid,nobiletin,paeonol and paeoniflorin were determined as the critical quality attributes of Huaganjian.Conclusion The critical quality attributes of Huaganjian identified in this study can provide a basis for the research and development of compound preparation.