有毒中药千金子需经去油制霜后入药用，炮制目的是减毒，但其减毒机理尚不明确。前期研究发现制霜后主要毒-效成分群二萜酯类含量降低，减毒机制与肠道炎性因子、P-gp、CYP450酶等因素密切相关，因此在中医药整体观的指导下，本项目创新性地将16S rDNA荧光定量PCR、UPLC-Q-TOF/MS等前沿技术引入炮制减毒机理研究，以肠道菌群微生态环境、药动学、内源性代谢组分动态变化为切入点，通过整体辨识和层次分析，构建“体内外”交叉代谢网络、药物与机体相互作用网络的整体关联性。本项目基于对千金子药性理论的认识和制霜解毒降毒、缓和药性的实践，从整体、组织、分子水平研究，以探明千金子制霜减毒，通过调控肠道菌群微生态环境、介导机体吸收、分布、代谢、排泄，以及机体内源性代谢组分时空变化与特异性代谢通路改变而发挥作用之假说的科学内涵，为其安全用药提供科学依据，也为炮制减毒作用机制研究提供新的思路与技术手段。

Semen Euphorbiae,one kind of toxic traditional Chinese medicine must be processed in order to reduce the toxicity and remove oil so that it could be taken safely.While the attenuated processing mechanism of traditional Chinese medicine is still not explicit. Our previous studies have found that the amount of major toxicity-active ingredient groups,Diterpenoid esters,decreased after processing and the key attenuated mechanism of Semen Euphorbiae were closely related to intestinal inflammatory factors,P-gp and CYP450 enzymes. Under the guidance of the overall concept of TCM, we introduced the16S rRNA quantitative PCR,UPLC-Q-TOF/MS and other forefront technology to the processing of traditional Chinese medicine field innovatively. Taking the gut micro-ecology,pharmacokinetics and the dynamic changes of the endogenous metabolic componet as starting point, we built and evaluated the overall correlation of metabolic networks in vivo and vitro, interaction network between drug and body by means of the overall identification and hierarchy-relation analysis.On the basis of the cognition of unique properties of Semen Euphorbiae and the practice of manufacturing pulveratum method for resolving and reducing toxicity, this project will study and clarify the attenuated mechanism of Semen Euphorbiae after processing from the overall, tissular and molecular levels, which the scientific connotation of the hypothesis will be expressed by regulating gut micro-ecology, mediating changes in time and space of ADME and endogenous metabolic components as well as changes in specific metabolic pathway in organism.This project will not only offer a scientific basis for the clinical safety of Semen Euphobiae,but also provide new thoughts and techniques for the study of toxicity-attenuated processing mechanism of traditional Chinese medicine.