摘要
Objective:Chuanxiong Rhizoma(CR,the dried rhizomes of Ligusticum chuanxiong)is a well-known traditional Chinese medicine that promotes qi to activate blood,dispels wind,and relieves pain.To date,more than 118 constituents of CR have been isolated and identified.However,the in vivo mechanism of CR decoction is unclear and needs further investigation.In addition,to clarify the effective forms of CR,it is essential to reveal the absorbed constituents and metabolites of CR.Materials and Methods:The absorbed constituents and metabolites in urine and plasma samples of rats orally administered with CR decoction were screened and characterized using a high-performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry technique.Results:In total,102 compounds,including 11 absorbed constituents(eight phthalides and three phthalic acids)and 91 metabolites(71 phthalide-related and 20 phenolic acid-related),were detected in drug-containing rat urine and plasma samples,among which 33 were new metabolites of either CR or its constituents.Based on the structures of these metabolites,six phthalides(ligustilide,senkyunolide I/H,senkyunolide J/N,and butylidenephthalide)and three phenolic acids(ferulic acid,isoferulic acid,and caffeic acid)were proposed as their precursors.They were also deduced to be the main absorbed constituents of CR decoction,which should have closer relationships with its pharmacological effects than other constituents.Phthalide-related metabolites were formed through the metabolic reactions of hydration,hydroxylation,cysteine conjugation,acetylcysteine conjugation,methanethiol conjugation,mercaptomethanol conjugation,glucuronidation,and sulfation,whereas the phenolic acid-related metabolites were mainly formed by glucuronidation and sulfation.Conclusions:Six phthalides and three phenolic acids were shown to be the main precursors of the metabolites of CR,and 33 compounds were new metabolites of either CR or its constituents.These results are helpful for further understanding of the in vivo mechanism and effective forms of CR.
基金
financially supported by the National Science and Technology Major Project for Major New Drugs Innovation and Development of China(No.2009ZX09502-006,No.2009ZX09301-010,No.2019ZX09201004-001-023)
the National Natural Science Foundation of China(Grant No.30830120,81473321)。
