功能代谢组学在中药毒性评价中的研究策略及其应用

Research strategy and application of functional metabolomics in toxicity evaluation of traditional Chinese medicine

传统中药因其具有整体观念、药效明确、辨证论治等特点而历史悠久。然而,当今中药毒性与安全用药问题引起研究者的广泛关注,中药毒性机制尚不明确,因此,迫切需要提出新的研究策略。功能代谢组学作为代谢组学的延伸,通过超高效液相色谱串联四级杆飞行时间质谱(ultra-high performance liquid chromatography-tandem quadrupole time-of-flight-mass spectrum,UPLC/Q-TOF-MS)技术检测机体受到中药干扰后产生的内源性代谢物,获得代谢标志物并结合其他技术手段筛选出代谢酶,随后,利用分子生物学实验验证代谢标志物及其关联酶之间的关系,阐释代谢物关联的下游毒性机制,形成一套“毒性成分-内源性代谢物-直接靶标-毒性机制”的新策略。近年来,大量功能代谢组学应用于探索中药的毒性机制,如肝、心脏、肾、肺等毒性。综述了功能代谢组学在中药提取物、中药单体毒性评价中的研究策略、毒性靶点及作用机制,为功能代谢组学在毒理学研究中的应用前景提供新方向。

Traditional Chinese medicine has a long history because of its holistic concept, clear medicinal effects and evidence-based treatment. However, the issue of toxicity and safe use of traditional Chinese medicines have attracted extensive attention from researchers, and the toxicity mechanism of traditional Chinese medicines is still unclear. Therefore, it is urgent to propose new research strategies. As an extension of metabolomics, functional metabolomics use ultra-high performance liquid chromatography-tandem quadrupole time-of-flight-mass(UPLC-Q-TOF/MS) technology to detect endogenous metabolites produced by the body after being interfered by traditional Chinese medicines, obtain metabolic markers, and screen out metabolic enzymes in combination with other technical means. Subsequently, molecular biology experiments were used to verify the relationship between metabolic markers and their associated enzymes, to explain the downstream toxicity mechanisms associated with metabolites, and to form a new strategy of “toxic ingredients-endogenous metabolites-direct targets-toxicity mechanisms”. In recent years, a large number of functional metabolomics have been devoted to exploring the toxicity mechanism of traditional Chinese medicine, such as liver, heart, kidney, lung and other toxicity. In this paper, the research strategies, toxicity targets and action mechanisms of functional metabolomics in the toxicity evaluation of Chinese medicine extracts and Chinese medicine monomers were reviewed, in order to provide a new direction for the application prospect of functional metabolomics in toxicology research.