基于代谢组学及网络药理学方法研究新疆罗勒抗动脉粥样硬化有效组分及作用靶点

Atherosclerosis is a vascular degenerative diseases caused by many reasons such as lipid metabolism disorders, inflammation, oxidative stress, endothelial injury. It is also one of the major causes of cardiovascular diseases (CVD). Ocimum Basilicum L. (OBL) has long been used to treat cardiovascular diseases in traditional Uyghur Medicine. In previous studies, we demonstrated that OBL extracts have antihyperlipidemic, antithrombotic, anti-inflammatory, vascular endothelial protection and antioxidant effects. Therefore, OBL may have anti-atherosclerotic effects by different pathways such as regulation of lipid metabolism, antioxidant and anti-inflammatory effects, etc. The effective components of OBL could have several targets in different pathways, which might regulate and connect with each others like a network. In this project we plan to screen the anti-atherosclerotic components by comprehensive assessment of metabonomics and give qualitative and quantitative analysis of effective components. The targets and signal pathways will be predicted by network pharmacology. This study should provide experimental evidence for the clinical application of OBL extracts. Importantly, our results will provide novel experimental and mechanistic data for future introduction of new drugs or nutritional products with high potency and low toxicity.

动脉粥样硬化是由于脂质代谢紊乱、炎症反应、氧化应激、内皮损伤等多种因素综合作用引起的血管退行性病变，导致CVD的重要病理基础。罗勒是传统维吾尔医学心血管疾病常用药物。本课题组研究发现新疆罗勒提取物具有调血脂作用、抗血栓作用、抗炎作用、血管内皮保护作用、抗氧化作用，推测罗勒可能通过改善脂质代谢紊乱、抗氧化、抗炎等途径发挥抗动脉粥样硬化作用，且可能包含多个有效成分多靶点的整合调节作用。因此本项目拟采用多药效指标综合评价和代谢组学相结合的方法，筛选罗勒抗AS的有效组分，对有效组分进行化学成分定性定量分析，并以网络药理学方法预测可能的作用靶点及信号通路。本项目研究结果可为罗勒临床用药提供科学依据，为开发高效低毒的新药或药食两用的保健品奠定一定工作基础。

动脉粥样硬化是由于脂质代谢紊乱、炎症反应、氧化应激、内皮损伤等多种因素综合作用引起的血管退行性病变，导致CVD的重要病理基础。研究内容 （1）罗勒总黄酮对ApoE-/-小鼠抗动脉粥样硬化作用及其机制研究。（2）利用1H-NMR代谢组学研究方法探讨罗勒总黄酮对ApoE-/-基因缺陷动脉硬化模型小鼠的影响。（3）基于系统网络药理学研究新疆罗勒挥发油的活性成分。（4）基于网络药理学研究罗勒黄酮类活性成分在心血管疾病中的作用及其机制。结果 （1）罗勒总黄酮在ApoE-/-动脉粥样硬化小鼠中可能通过调节炎症反应、脂质代谢、能量代谢、氨基酸代谢紊乱而发挥一定的防治动脉粥样硬化作用。（2）与模型组相比较血清及尿液的罗勒总黄酮低、中、高三组对上述代谢物有一定程度的逆转，表明罗勒总黄酮可能通过ApoE-/-动脉粥样硬化小鼠的胆碱、氨基酸、胆固醇及能量代谢对动脉硬化病症有一定的调控和改善作用。（3）罗勒挥发油活性成分主要通过5 个信号通路作用于皮肤病、癌症、心脑血管疾病等。（4）罗勒黄酮类活性成分主要通 过DYRK1A, SLC5A11, SLC5A10, SLC5A9, ERBB2, MBNL3, MBNL2, AKR1E2 等不同靶点，经 Cgmp-PKG 信号通路、钙信号通路，甘油脂代谢等途径作用于 心脏病、高血压，心肌梗死、动脉粥样硬化等心血管疾病。结论 本项目研究结果可为罗勒临床用药提供科学依据，为开发高效低毒的新药或药食两用的保健品奠定一定工作基础。