基于预测数据库发现中药灯盏生脉在大鼠体内的代谢产物的新分析策略研究  

Novel strategy in Dengzhan Shengmai capsule metabolites analysis based on the prediction database

作　　者：李元元 郑博文 马聪玉 生宁 张金兰 LI Yuan-yuan;ZHENG Bo-wen;MA Cong-yu;SHENG Ning;ZHANG Jin-lan(State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《药学学报》2023年第8期2468-2475,共8页Acta Pharmaceutica Sinica

基　　金：中国医学科学院医学与健康科技创新工程项目(2022-I2M-2-002);国家自然科学青年基金资助项目(82204341);科技部重点研发计划(2019YFC1708901).

摘　　要：灯盏生脉胶囊是一种复方中成药,由灯盏细辛、人参、麦冬和五味子四味药材组成,包含了黄酮类、木脂素类、皂苷类及有机酸类等药效成分。其临床应用广泛,主要用于治疗缺血性心脑血管疾病、痴呆等疾病。本研究提出了一种基于预测数据库对多成分中药代谢产物鉴定的研究策略,并以灯盏生脉胶囊为例展开研究。具体研究策略为:基于灯盏生脉预测代谢产物数据库,使用高分辨率UPLC-Q-TOF/MS分析方法分析给药前后大鼠胆汁、尿液和粪便等生物样本,通过分析结果与数据库对比识别可能的代谢产物,并基于原型成分质谱裂解规律、一级和二级高分辨离子信息对代谢产物进行鉴定。最终在大鼠胆汁、尿液和粪便样本中共鉴定51个灯盏生脉代谢产物,主要类别为黄酮类、有机酸类和木脂素类代谢产物。本研究为中药及其复方体内代谢产物鉴定及代谢途径分析提供了新策略,为全面识别和鉴定活性成分代谢产物,以深入了解中药体内代谢机制提供了切实可行的手段。实验遵守中国医学科学院药物研究所的动物实验伦理委员会制定的规程(动物实验伦理审查编号:No.00003645)。Dengzhan Shengmai capsule,as a compound Chinese patent medicine,consists of four herbs:Herba Erigerontis,Ginseng,Ophiopogon,and Schisandrae Chinensis Fructus,and contains significant components of flavonoids,lignans,saponins,and organic acids.It is widely used clinically to treat cerebrovascular diseases such as chronic cerebral hypoperfusion and dementia with remarkable efficacy.This study proposes a research strategy for multi-component traditional Chinese medicine metabolites based on prediction databases and unfolds the analysis using Dengzhan Shengmai capsule as an example.Using the UPLC-Q-TOF/MS method,the analytical method was established and detected biological samples such as urine,feces,and bile of rats before and after administration based on the prediction of theoretical metabolites of Dengzhan Shengmai capsule.The possible secondary fragment ion information of metabolites was identified by comparing the detected results with prediction databases.The metabolites were identified based on the archetypal component mass spectrometric cleavage law and multistage mass spectrometric data.51 metabolites,mainly flavonoid,organic acid,and lignan constituents,were finally identified from rat biosamples based on 306 theoretical metabolites of Dengzhan Shengmai capsule.This study provides a new strategy for the identification of metabolites in vivo and the analysis of metabolicpathways of TCM. The study complied with the procedures established by the Animal Experiment Ethics Committeeof the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethicsexamine (No. 00003645).

关 键 词：灯盏生脉 超高效液相色谱-飞行时间质谱联用 代谢产物鉴定 中药代谢 

分 类 号：R917[医药卫生—药物分析学]