蒙药肋柱花对高脂饮食诱导肥胖大鼠的减肥功效及其苦味机制研究

Obesity is a chronic metabolic disease that influences the largest population in the world. According to the Traditional Mongolian Medicinal Theory, bitter taste has the effect of reducing fat and improving the gut function. Our previous studies showed that the perception of bitter taste in the mouth reduced the appetite and induced rejection response. However, an adaptation has been occurred in a very short time. In addition, gastrointestinal bitter stimulation resulted in various physiological activities, such as influencing hormonal secretion, gastrointestinal motility and nutrition absorption etc. These effects may have important implications for long-term control of appetite, energy homeostasis and the prevention of obesity. Thus, in this project, we choose a classical Mongolian Medicine Lomatogonium Rotatum which taste as a bitterness, and to test the anti-obesity effect in a high-fat diet induced obese rat model. Then, we will aim to investigate the potential mechanism relate to gastrointestinal motility and bitter taste receptor signaling pathway. Finally, we will discuss the relationship between Lomatogonium anti-obesity mechanism and the medicinal flavor theory of traditional Mongolian medicine. Overall, this project will investigate the medicinal flavor theory of Mongolian medicine through modern science and technology approaches, which is of great significance to the modernization development of Mongolian medicine basic theory.

肥胖是世界上涉及人口最多的慢性代谢性疾病。蒙药苦味药性理论认为苦味药性具有燥腐消脂作用，且可增强胃肠功能。我们研究发现，口腔苦味感知可以降低食欲并产生排斥反应。但在短时间将产生耐受性。胃肠道苦味刺激可导致体内荷尔蒙分泌，胃肠动力减缓以及促进营养吸收等生理功能。这些作用可能对长期控制食欲、能量代谢以及治疗肥胖症具有重要意义。因此，本课题以特色苦味蒙药肋柱花为示例药物，以高能量饮食诱导肥胖模型大鼠为研究对象，佐证肋柱花苦味物质减肥功效的同时从分子基因水平及T2Rs信号通路探讨肋柱花调节胃肠运动作用机理，进而探讨肋柱花减肥作用机制与蒙药药味药性理论之间的相关性。本课题通过现代科学技术手段揭示蒙药药性药味理论，对蒙医药基础理论现代化发展具有重要意义。

蒙药苦味药性理论认为苦味药性具有燥腐消脂和调节胃肠动力之功效。胃肠道苦味刺激可致体内荷尔蒙分泌，调节胃肠动力和小肠营养吸收等生理功能，对控制食欲、能量代谢以及防治肥胖症和胃肠动力疾病具有重要意义。本课题以特色苦味蒙药肋柱花为示例药物，以高脂高能量饮食诱导肥胖模型大鼠为研究对象，佐证肋柱花苦味素减肥降脂功效的同时从分子基因水平及T2Rs信号通路探讨肋柱花调节胃肠动力作用机理，进而探讨肋柱花减肥降脂、调节胃肠动力作用机制与蒙药药味药性理论之间的相关性。.首先，通过化学成分和味觉属性分析证实肋柱花主要苦味成分为獐牙菜素、獐牙菜苷、橙皮素、1.7-二羟基-3.8-二甲氧基口山酮、羟甲基香豆素、槲皮素和山奈酚等7种成分。正交试验优选肋柱花苦味素制备工艺后苦味成分含量达66%。肥胖大鼠减肥验证实验表明肋柱花苦味素具有显著调节胃肠动力和减肥降脂作用，上调胃肠道苦味受体表达，良性调节肠道菌Ruminococcaceae、Akkermansiaceae和Lachnospiraceae及其代谢物Momordenol、Elaidic carnitine，Pyridoxal、Mevalonic acid-5P、Phosphrylcholine、Albanol B、Pterolactam、Cryptodorine、Se-Adenosylselenohomocysteine等，参与调控脂肪代谢、信号传导、能量代谢、萜类和多酮类代谢等，从而控制肥胖、抑制内脏脂肪沉积和调控胃肠动力功能。其次，在胃肠动力体内外实验中，我们惊喜的发现肋柱花苦味素可以双向调节胃肠动力，即低浓度范围内收缩胃肠动力，而达到一定浓度之后则舒张胃肠动力，且与激活苦味信号通路相关。细胞实验进一步验证了肋柱花苦味素调节胃肠动力功能与激活苦味信号通路因子和细胞内钙离子浓度升高密切相关。因此，胃肠道苦味受体可作为防治胃肠动力疾病和肥胖症的潜在药用靶点。 .本课题围绕蒙药苦味药性“燥腻消脂”和调节胃肠动力功效理论，通过化学、药理、分子细胞学、多组学联合技术，首次探讨特色苦味蒙药肋柱花减肥、降脂、调节胃肠动力功效及其苦味通路机制，为特色民族药物开发应用和传统基础理论的现代化阐释提供了新的研究思路和科学方法。