中文摘要
近年来,菊三七属的多种植物在民间被广泛食用,用于防治糖尿病效果显著。前期化学成分的比较研究提示,黄酮、萜类和酚酸类化合物为该属降糖植物的共有显效成分,而药效研究尚停留在单个植物宏观提取物的降糖评价或单一化合物的简单靶点活性筛选,忽略了该属内不同物种间共有显效成分的异同比较和统一评价,造成该属植物降糖药效成分未能全面准确理解。本项目拟以菊三七属中已被证实具有降糖效果的四种植物为研究对象,采用组合比较和代谢组学相结合的研究方法,对其共有显效成分开展针对2型糖尿病模型动物的生物学活性评价,通过对生物样品代谢物的动态分析,结合糖尿病相关生理生化指标,利用多变量相关分析,从中筛选与抗糖尿病疗效密切关联的代谢物靶标和代谢轮廓,并以此为指导追寻与显效成分变化的关联性,解析其确切有效成分(群)及作用机制。同时,项目将考察肝毒性PAs成分在该属植物内的分布规律,并进行体内毒性评价,为其安全利用提供科学依据。
英文摘要
Recently, some species in plants of Gynura Cass attract many attentions for their use for the prevention and treatment of diabetes mellitus in China. In previous phytochemical reports, the wide presence of flavonoids, terpenes and phenolics was reported among these plants. A variety of research efforts in the past were focused on evaluating total extracts through pharmacological methods or isolating single constituents for single-targeted in vitro bioassay. However, they disregarded the combinatorial role and integrative therapeutic effects of multiple active compounds. The exact composition of hypoglycemic components in Gynura plants is remained to be resolved. In this work, we propose a hypothesis that bioactive components accounting for the similar anti-diabetic efficacy of these Gynura species could be discovered from a combination of their mutual constituents (flavonoids, terpenes and phenolics), by applying a metabolomics strategy to profile the metabolites in typical T2DM mice using HPLC-TOF/MS coupled to partial least square-discriminant analysis. Moreover, the nontargeted metabolomics profiling will reveal the effect of these chemical combinations, with diverse perturbed metabolites being correlated with antidiabetic activities, to discover the novel mechanism of action and related biomarkers. This work helps to offer evidence-based data to answer the key questions of which are real bioactive components for Gynura Cass. plants that could been used for diabetes treatment.
