Comparative Analysis of the Gelsemium Alkaloids Metabolism in Human, Pig, Goat, and Rat Liver Microsomes

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current drug metabolism Pub Date : 2024-04-04 DOI:10.2174/0113892002298633240322071126

Yi-Rong Wang, Meng-Ting Zuo, Wen-Bo Xu, Zhao-Ying Liu

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Abstract

Aim: 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 microparticles 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. Conclusion: 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. result: 46 natural products were characterized from alcohol extract of Gelsemium elegan and 13 metabolites were identified. 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, but no oxidative metabolites of Gelsedine-type alkaloids were detected in goat and human.

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人、猪、山羊和大鼠肝脏微粒体中的格列齐特生物碱代谢对比分析

目的：本研究旨在调查人、猪、山羊和大鼠肝脏微粒体中的格尔木代谢，并阐明不同物种间格尔木生物碱的代谢途径和裂解模式。研究方法体外培养人、山羊、猪和大鼠肝脏微粒体。在 37°C 下孵育 1 小时并离心后，用 HPLC/Qq-TOFMS 对处理后的样品进行检测，以检测 Gelsemium elegans 的醇提取物及其代谢物。结果鉴定了46种 elegans Gelsemium 酒精提取物的天然产物，并确定了13种代谢物。这 13 种代谢物属于 Gelsemine、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各不相同。在猪和大鼠的微粒体中检测到了全部 13 种代谢物，但在山羊和人的微粒体中没有检测到 Gelsedine 类生物碱的氧化代谢物。结论本研究阐明了不同物种中的凝胶苣苔代谢模式，并对凝胶苣苔的体外代谢进行了研究。研究结果：从大叶黄杨的醇提取物中鉴定出 46 种天然产物，并确定了 13 种代谢物。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。在猪和大鼠中检测到了全部 13 种代谢物，但在山羊和人中没有检测到 Gelsedine 类生物碱的氧化代谢物。

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来源期刊

Current drug metabolism 医学-生化与分子生物学

CiteScore

4.30

自引率

4.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.