ABSTRACT
Objective: To investigate and characterize the O-glucuronidation pathways of the S-stereoisomer of shikonin (alkannin). Methods: Liquid chromatography and mass spectrometry were employed for the detection of akannin and its glucuronide. The incubation of alkannin in human liver microsomes (HLM), human kidney microsomes (HKM) and recombinant human UDP-glucuronyltransferases (UGT) were employed for the study of metabolism profile, the involved UGT isoforms and kinetic analysis. Recombinant human UGT screening, correlation study and chemical inhibition experiments were used for elucidation the selectivity of UGT isoform towards alkannin. Results: In the incubation of alkannin in HLM with the presence of UDPGA, a single UGT metabolite was detected. The screening of the recombinant human UGTs found that UGT1A9 high selectively catalyzed the glucuronidation of alkannin. Kinetic analysis revealed the kinetic of alkannin in HLM, HKM and recombinant UGT1A9 all followed substrate inhibition model and the Km values were 3.75-4.50 μmol/L. The glucuronidation of alkannin and propofol, a probe substrate of UGT1A9, in 12 individual HLM showed really good correlation, the correlation coefficient R2 was 0.88. Chemical inhibition experiments indicated that HLM magnolol and niflumic acid showed obvious inhibition to alkannin glucuronidation; Testerone, celastrol, and nilotinib did not inhibit alkannin glucuronidation. Conclusion: This study finds that UGT metabolism is an important metabolism pathway of alkannin in human, and alkannin is a highly selective probe substrate of human UGT1A9.
ABSTRACT
Objective To design a reproducible solution for municipal population health information platform to solve the problems in multi facilities involved,long construction period and etc.Methods The present situation of municipal health information platform was described as "eight manys and eight insufficiencys",and the solutions of foreign countries and China were explored from the aspects of business and technology architectures as well as the requirements of national population health informatization overall architecture.Results The municipal medical informatization infrastructure optimized regional medical service flow,improved medical resources allocation and enhanced health management.Conclusion Municipal population health information platform contributes to promoting regional medical service to meet increasing public requirements.