目的:本研究的目的是研究秀丽隐杆线虫在人体中的代谢,猪,山羊和大鼠肝微粒体,并阐明不同物种之间Gelsemium生物碱的代谢途径和裂解模式。
方法:人类,山羊,在体外培养猪和大鼠肝脏微粒。在37°C下孵育1小时并离心后,采用HPLC/Qq-TOFMS对处理后的样品进行检测,以检测秀丽线虫醇提物及其代谢产物。
结果:从线虫醇提取物中鉴定出46种天然产物,并鉴定出13种代谢产物。这13种代谢物属于明胶,koumine,gelsedine,humantenine,yohimbane,和sarpagine类生物碱。代谢途径包括氧化,去甲基化和脱氢。经过初步鉴定,在四个物种中检测到的代谢物是不同的。在猪和大鼠微粒体中检测到所有13种代谢物,但是在山羊和人微粒体中未检测到Gelsedine型生物碱的氧化代谢产物。
结论:在这项研究中,阐明了线虫在不同物种中的代谢模式,并研究了线虫的体外代谢。对其临床开发和合理应用具有重要意义。
OBJECTIVE: The aim of this study was to investigate the metabolism of Gelsemium elegans in human, pig, goat and rat liver microsomes and to elucidate the metabolic pathways and cleavage patterns of the Gelsemium alkaloids among different species.
METHODS: A human, goat, pig and rat liver microsomes were incubated in vitro. After incubating at 37°C for 1 hour and centrifuging, the processed samples were detected by HPLC/Qq-TOFMS was used to detect alcohol extract of Gelsemium elegans and its metabolites.
RESULTS: Forty-six natural products were characterized from alcohol extract of Gelsemium elegans and 13 metabolites were identified. These 13 metabolites belong to the gelsemine, koumine, gelsedine, humantenine, yohimbane, and sarpagine classes of alkaloids. The metabolic pathways included oxidation, demethylation and dehydrogenation. After preliminary identification, the metabolites detected in the four species were different. All 13 metabolites were detected in pig and rat microsomes, but no oxidative metabolites of Gelsedine-type alkaloids were detected in goat and human microsomes.
CONCLUSIONS: In this study, Gelsemium elegans metabolic patterns in different species are clarified and the in vitro metabolism of Gelsemium elegans is investigated. It is of great significance for its clinical development and rational application.