本项目选择毒性大、效果好、毒效关系密切的常用中药附子作为研究对象，首次提出中药“毒效”多维评价与整合分析的研究思路，围绕附子毒效共同的靶部位，建立病证结合模型、离体靶器官模型和靶细胞、干细胞、斑马鱼模型；应用化学生物学技术，研究附子的多重“毒效”物质基础，研究附子不同组分、不同成分、不同配伍组合对机体不同病证状态、不同层面（整体、器官、细胞、分子）的毒效作用和增效减毒原理；应用高内涵、组学方法，研究附子的作用靶点、作用强度、作用环节和“时-效-毒”与“量-效-毒”的时空关系；应用系统毒理学、网络药理学方法，构建附子“成分-靶点-活性”网络和“成分-靶点-毒性”网络，阐明附子“治疗心衰与心脏毒性”、“治疗风湿痹痛与神经毒性”、“治疗妊娠疾病与胚胎毒性”的内在机制，揭示附子毒效整合作用的科学内涵，为临床安全合理应用提供科学依据。

The project selects Fuzi (the lateral roots of Aconitum carmichaelii Debx.), a common traditional Chinese medicine with great toxicity, good efficacy, and close toxicity-efficacy relationship, as the research object. The applicant first proposes the research thought of multidimensional evaluation and integrated research on "toxicity and efficacy" of traditional Chinese medicines. Focusing on the same targets of the toxicity and efficacy of Fuzi, the project will establish animal models of combination of diseases and syndromes, target organ models in vitro, and models of target cells, stem cells, and zebra fish. By using modern chemistry and biology techniques, the project will not only study the multiple toxic-pharmacodynamic material bases of Fuzi, but also research the toxic-pharmacodynamic effects, as well as the efficacy-enhancing and toxicity-reducing principles of different chemical portions, different components, and different prescription compatibilities of Fuzi, for different disease status and different levels (including integral, organismal, cellular, molecular levels). Meanwhile, in this project, the high content screening (HCS) and omics methods will be used to research the action targets, intensity, and process, together with the relationships of “time-efficacy-toxicity” and “quality-efficacy-toxicity” of Fuzi. In addition, systematic toxicology and network pharmacology methods will be applied to construct the network of “components-targets-activities” and “components-targets-toxicities” of Fuzi. These results are expected to illuminate the internal mechanisms of “heart failure therapy and cardiotoxicity”, “rheumatic arthralgia therapy and neurotoxicity”, and “pregnant diseases therapy and embryotoxicity” of Fuzi, and reveal the scientific intension of the integration of toxicity and efficacy, which can provide scientific basis for safe and rational use of Fuzi clinically.