Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic absorbed constituents in rat plasma after oral administration of CP extract.However,their structures were unclear due to the presence of various isomers and the lack of reference standards.In the present study,an MS-guided targeted isolation of pyrrolidine alkaloids of CP extract was performed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC/Q-TOF MS).For data analysis under fast data directed acquisition mode(Fast-DDA),an effective approach named characteristic fragmentation-as-sisted mass spectral networking was successfully applied to discover new pyrrolidine alkaloids with high MS response in CP extract.As a result,seven new pyrrolizidine alkaloids[codonopyrrolidiums C-1(3-9)],together with two known ones(1 and 2),were isolated and identified by NMR spectral analysis.Among them,codonopyrrrolidium B(1),codonopyrrolidium D(4)and codonopyrrolidium E(5)were evaluated for lipid-lowering activity,and they could improve high fructose-induced lipid accumulation in HepG2 cells.In ad-dition,the characteristic MS/MS fragmentation patterns of these pyrrolizidine alkaloids were investigated,and 17 pyrrolidine alkaloids were identified.This approach could accelerate novel natural products discovery and characterize a class of natural products with MS/MS fragmentation patterns from similar chemical scaffolds.The research also provides a chemical basis for revealing in vivo ef-fective substances in CP.

TANG Xiyang;FAN Cailian;ZENG Jiaxing;ZHAO Pengcheng;WANG Xiaoxing;CAI Wanjun;LI Ting;DAI Yi;YAO Zhihong;YAO Xinsheng

College of Pharmacy and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry ofEducation,Jinan University,Guangzhou 510632,China;College of Medicine,Henan Engineering Research Center of Funiu Mountain's Medicinal Resources Utilization and Molecular Medicine,Pingdingshan University,Pingdingshan 467000,China

中国天然药物

[1]TANG Xiyang;FAN Cailian;ZENG Jiaxing;ZHAO Pengcheng;WANG Xiaoxing;CAI Wanjun;LI Ting;DAI Yi;YAO Zhihong;YAO Xinsheng-.Targeted isolation and identification of bioactive pyrrolidine alkal-oids from Codonopsis pilosula using characteristic fragmentation-assisted mass spectral networking)[J].中国天然药物,2022(12):948-960

alkal,codonopyrrolidiums,codonopyrrrolidium,codonopyrrolidium

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