中文摘要
高脂血症是一种由脂质紊乱导致机体代谢失衡的常见慢性疾病。本项目拟在前期研究基础和技术积累上,以中医药整体观和系统生物学为指导,应用现代药理学、网络生物学、化学计量学等多学科手段,开展广陈皮药材降脂活性的效应物质基础研究,并从肠道菌群和代谢组学角度系统研究广陈皮降血脂的分子作用机制。在全面表征广陈皮药材体内外化学物质基础上,构建基于Peak-cutting样品制备技术的中药降脂活性成分高通量筛选平台,应用“成分缺失/捕获-谱效集成表征”技术,快速制备广陈皮潜在降脂效应物质群;利用细胞模型、整体动物模型对广陈皮制备组分(群)进行体内外降脂活性评价,发现和确认其降脂活性成分群;进而从代谢组学和肠道菌群角度,筛选疾病和药物干预相关的生物标记物和网络靶标,揭示肠道菌群在高脂血症发生发展与药物治疗中的意义,最终系统阐明广陈皮药材降脂作用机制与化学内涵。
英文摘要
Hyperlipidemia is a chronic disease characterized by the lipid metabolism disorders. Guided by the holistic concept of Traditional Chinese Medicine and systems biology, and based on our previous research achievements and accumulation, utilizing the multi-disciplinary means including pharmacology modern, network biology and chemistry metrology, the present project aimed to uncover the hypolipidemic active constituents and mechanism of Guangchenpi (the dried pericarps of citrus reticulata 'Chachi') from the perspective of intestinal microflora and metabolomics. After characterizing the in vitro and in vivo active constituents in Guangchenpi, we planned to construct a hypolipidemic activity high throughput screening platform by Peak-cutting sample preparation. By applying the "chemical markers fishing and knockout/spectrum-effect integrated characterization" technique, we may rapidly discover the hypolipidemic active constituents and mechanism of Guangchenpi; The cell model and the whole animal models are employed to evaluate and confirm the hypolipidemic activity of the prepared constituents (groups). Later, from the perspective of metabolomics and intestinal flora, we designed to screen the related biomarkers and target network with disease and drug intervention, and reveal the significance of intestinal flora in the development of hyperlipidemia and drug therapy, and finally clarify the hypolipidemic mechanism of Guangchenpi.
