基于多组分代谢与残留的钩吻作用物质基础研究

钩吻是用来治疗神经痛和癌症的传统中药，对人有剧毒。但对于猪和羊等食品动物食之有益，在养殖业中常作为饲料添加剂使用。目前，尚未从整体上揭示钩吻在猪的作用物质基础这一关键科学问题。因此，本项目采取基于多组分代谢与残留的中药作用物质基础研究新思路，在我们前期钩吻化学成分鉴定与主要有效成分体外代谢的基础上。建立钩吻多组分在血液和组织中同时定量的LC-MS/MS检测方法；利用LC-QqTOF-MS结合多种代谢分析策略，研究钩吻多组分在猪体内的代谢变化规律；研究其在猪体内的吸收、分布、代谢与排泄的动态变化规律，并结合血浆药理学，探索钩吻整体药代-药效特征；研究钩吻多组分在猪的残留消除规律，揭示其残留部位和残留标示物；并利用代谢组学技术研究钩吻作用前后机体的代谢物变化，表征钩吻的作用模式和相关机制。从药代、残留和代谢组学三方面阐明钩吻作用的物质基础，为钩吻药理与毒理作用机制研究和安全性评价提供科学依据。

Gelsemium elegans (G. elegans ) has been used as traditional Chinese medicine (TCM) for the treatment of neuralgia and cancer for many years. It is very poisonous to human being. However, G. elegans has been recognized a beneficial plant to food animals such as pigs and sheep. It has been widely used as feed additives in livestock breeding. Currently, the key scientific problem on the material basis of G. elegans in pig has not been revealed yet. Therefore, this project introduces the new strategy and approach to study the material basis based on multiple components metabolism and residues. Recently, we have identified chemical profiling of G. elegans extracts and in vitro metabolites of active components in animals. Based on these results, the sensitive and reliable LC-MS/MS methods for simultaneously determination of multiple components of G. elegans in porcine plasma and tissues will be developed and validated in the project. The metabolic characteristics of G. elegans extracts with multiple components in pig will be further researched by the combination of quadrupole time-of-flight tandem mass spectrometry (LC-QqTOF-MS) with various metabolic analysis strategies. The dynamic changes of metabolism, absorption, distribution and excretion of G. elegans with multiple components in pigs will be examined in detail using the developed methods. The pharmacokinetic-pharmacodynamic characteristics of G. elegans will be explored based on its plasma pharmacology. We will also reveal the residual sites and marker residues by the research of residue depletion of G. elegans with multiple components in pig tissues. The changes of endogenous metabolites in pig biological system after oral administration of G. elegans will be investigated using a metabolomics strategy. The action patterns and related mechanisms of G. elegans will be characterized. The material basis of G. elegans will be revealed from three aspects of pharmacokinetics, residues and metabonomics. The relevant findings will lay the scientific basis for pharmacological and toxicological mechanism and its safety evaluation of G. elegans in the future.