基于UPLC-Q-Exactive MS技术太子参环肽heterophyllin A、pseudostellaria C在大鼠体内的代谢产物及代谢途径研究  

Study on metabolites and metabolic pathways of Pseudostellaria heterophylla cyclic peptides heterophyllin A and pseudostellaria C in rats by UPLC-QExactive MS technology

作　　者：赵立 阚永军 蒋畅 庞文生[3] 胡娟 ZHAO Li;KAN Yongjun;JIANG Chang;PANG Wensheng;HU Juan(Institute of Pharmaceutical Sciences,Fujian Academy of Chinese Medical Sciences,Fuzhou 350003,China;Department of Pharmacy,The Second People's Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou 350003,China;School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建省中医药科学院药物研究所,福建福州350003 [2]福建中医药大学附属第二人民医院药学部,福建福州350003 [3]福建中医药大学药学院,福建福州350122

出　　处：《药物评价研究》2024年第11期2585-2596,共12页Drug Evaluation Research

基　　金：福建省省属公益类科研院所科研专项项目(2021R1003006);福建省自然科学基金项目(2021J01913,2020J01723);国家重点研发计划“中医药现代化研究”重点专项(2019YFC1710504)。

摘　　要：目的分析鉴定大鼠ig太子参环肽提取物后血浆、胆汁、尿液及粪便的代谢产物,并推测其在大鼠体内的代谢途径。方法雄性SD大鼠ig太子参环肽类提取物(400 mg·kg^(−1)),给药后收集血浆、胆汁、尿液及粪便样品。样品处理后,采用超高效液相色谱-四极杆-静电场轨道离子阱质谱技术(UPLC-Q-Exactive MS)分析环肽的入血原型成分,对其中2种入血环肽heterophyllin(HA)、pseudostellaria C(PC)代谢物进行结构表征。结果共从大鼠血浆中提取到了7种环肽类成分,包括pseudostellarin A、pseudostellarin B、heterophyllin B、PC、pseudostellarin D、HA、pseudostellarin E;在大鼠的生物样本中检测到13个HA代谢产物,其中血浆、胆汁、尿液、粪便分别鉴定出3、7、0、13个;PC代谢产物有15个,其中血浆、胆汁、尿液、粪便分别有3、10、4、14个。2种环肽在大鼠体内存在去羟基化、水解、脱水、甲基化代谢途径。结论通过UPLCQ-Exactive MS技术推测出了HA和PC代谢产物和途径。Objective To analyze and identify the metabolites present in plasma,bile,urine and feces after gavage of the cyclic peptide extract of Pseudostellaria heterophylla and to speculate on the metabolic pathways of different structural cyclic peptides in rats.Methods Male SD rats were ig administered cyclic peptide extract(400 mg·kg^(−1)),and plasma,bile,urine and feces samples were collected.After the samples were processed,the metabolites of two of the blood entry cyclic peptides,heterophyllin A(HA)and pseudostellaria C(PC)were structurally characterized by ultra-high-performance liquid chromatography-quadrupoleelectrostatic field orbital ion trap mass spectrometry(UPLC-Q-Exactive MS).Results Seven cyclic peptide components were extracted from plasma,including pseudostellarin A,pseudostellarin B,heterophyllin B,PC,pseudostellarin D,HA,and pseudostellarin E.13 metabolites of HA and 15 metabolites of PC were detected in biological samples from rats.3,7,0,and 13 of HA metabolites and 3,10,4,and 14 of PC metabolites were identified in plasma,bile,urine,and feces,respectively,and the metabolism of the two cyclic peptides in rats was elucidated through the pathways of dehydroxylation,hydrolysis,dehydration,and methylation.Conclusion The metabolites of HA and PC were deduced by UPLC-Q-Exactive MS.

关 键 词：太子参环肽 超高效液相色谱-四极杆-静电场轨道离子阱质谱技术 heterophyllin A pseudostellaria C 代谢产物 代谢途径 

分 类 号：R917[医药卫生—药物分析学]