A Microbial Transformation Model for Simulating Mammal Metabolism of Artemisinin

Molecules

Lan Yang¹  Yue Bai¹  Yue Ma¹  Yifan Zhao¹  Xiaoqiang Chang¹  Peng Sun¹  Kun Wang¹  Dong Zhang¹ 

[1] Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;

关键词: microbial transformation;    Cunninghamella elegans;    metabolite;    identification;    artemisinin;    UPLC-ESI-Q-TOF-MSE;    UNIFI software;    in vivo;   

DOI  :  10.3390/molecules24020315

来源: DOAJ

【 摘 要 】

Artemisinin (ART) is a highly effective antimalarial agent isolated from the traditional Chinese herb Qinghao. Metabolism of ART and its derivatives in the body is one of the most pressing issues for pharmaceutical scientists. Herein, an efficient in vitro microorganism model for simulation of metabolism of ART in vivo was developed employing Cunninghamella elegans. Metabolites in the microbial transformation system and plasma of mice pre-administrated ART orally were analyzed by ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-quadrupole time-of-flight (Q-TOF)-mass spectrometry (MSE) combined with UNIFI software. Thirty-two metabolites were identified in vitro and 23 were identified in vivo. After comparison, 16 products were found to be common to both models including monohydroxylated ART, dihydroxylated ART, deoxyartemisinin, hydroxylated deoxyartemisinin, hydroxylated dihydroartemisinin (DHA), and hydroxylated deoxy-DHA. These results revealed that C. elegans CICC 40250 functioned as an appropriate model to mimic ART metabolism in vivo. Moreover, an overall description of metabolites of ART from C. elegans CICC 40250 has been provided. Notably, DHA was detected and identified as a metabolite of ART in mouse plasma for the first time.

【 授权许可】

Unknown