Pregnane and Glycosides and Obesity/llya Raskin

项目总结(见说明)： 体重失调的许多病理生理机制可以通过调节能量平衡中的中央调节元件来管理，包括食物摄入量和能量消耗。尽管缺乏临床前、临床和毒理学研究，但含有从沙漠马利筋植物中提取的富含孕烷苷的膳食补充剂仍是最受欢迎的植物减肥药物之一。 研究证据。为了验证富含孕烷糖苷的植物的生理和药理作用，我们筛选了属于乳草家族的植物，并确定沼泽乳草Asclepias incarnata是Hoodia的常见和快速生长的北美近亲，作为活性成分的替代来源。答：龙须菜提取物导致食物摄入量急剧减少，从而减少脂肪沉积，改善胰岛素敏感性标记物，可能是通过一种需要通过初级迷走神经传入进行肠脑沟通的机制。用提取物进行长期治疗和配对喂养以控制其对食物摄入量的影响的研究支持了提取物的额外代谢作用，而不依赖于其对食物摄入量的影响。基于这些观察，我们假设化身素通过促进饱腹感和刺激能量消耗来影响能量平衡。因此，我们的主要目标是了解这种植物通过三个具体目标来增加饱腹感和延缓进展为代谢综合征的机制(S)的互补成分：1)通过以下三个具体目标确定作用部位和机制(S) 2)确定肉质素抗肥胖作用的能量消耗机制；3)利用受控条件下人体消化系统的功能模型，确定肉质素类及其生物活性成分(S)的生物利用度，并评价其构效关系 使用细胞培养分析的特性

PROJECT SUMMARY (See Instructions): Many pathophysiological mechanisms that underlie weight disorders can be managed through modulation of central regulatory elements in energy homeostasis, including food intake and energy expenditure. Dietary supplements that contain pregnane glycoside-enriched extract from a desert milkweed plant Hoodia are among the most popular botanical weight-loss remedies despite the lack of pre-clinical, clinical, and toxicological research evidence. To validate the physiological and pharmacological effects of pregnane glycoside-enriched botanicals, we screened plants that belong to milkweed family and identified swamp milkweed, Asclepias incarnata, a common and fast growing North American relative of Hoodia, as an alternative source of active ingredients. A. incarnata extract produced an acute reduction in food intake that reduced fat deposition and improved markers of insulin sensitivity, possibly through a mechanism requiring gut-brain communication via primary vagal afferents. Studies involving chronic treatment with the extract and pair feeding to control for its effect on food intake supported an additional metabolic role of the extract independent of its effects on food intake. Based on these observations, we hypothesize that incarnatin impacts energy homeostasis by promoting satiety and stimulating energy expenditure. Thus our primary goal is to understand the complementary components of the mechanism(s) by which this botanical enhances satiety and attenuates the progression to metabolic syndrome through three specific aims: 1) To identify the site of action and mechanism(s) through which incarnatin controls food intake; 2) To determine the mechanisms of energy expenditure in the antiobesity activity of incarnatin; 3) To define bioavailability of incarnatin and its bioactive component(s) using a functional model of the human digestive system under controlled conditions and evaluate their structure-activity properties using cell culture assays