Ginsenocide Rb1: A Novel Anti-Obesity and Anti-Hyperglycemic Compound

人参皂苷 Rb1：一种新型抗肥胖和抗高血糖化合物

• 批准号: 8996168
• 负责人: Min Liu
• 金额: $ 32.97万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8996168
• 关键词: Acute; Adipose tissue; Adverse effects; Alternative Medicine; Antidiabetic Drugs; Area; Asians; Blood - brain barrier anatomy; Blood Glucose; Body Weight; Brain; Brain region; Chronic; Chronic Disease; Clinical; Clinical Research; Clinical Trials; Complex; Country; Data; Diabetes Mellitus; Dose; Eating; Epidemic; FOS gene; Fasting; Future; Ginseng Preparation; Herbal supplement; High Fat Diet; Homeostasis; Human; Hyperglycemia; Hypothalamic structure; Incidence; Intraperitoneal Injections; Knowledge; Leptin; Leptin resistance; Mediating; Medicine; Metabolic Diseases; Metabolic syndrome; Middle Hypothalamus; Neurons; Neuropeptides; Non-Insulin-Dependent Diabetes Mellitus; Nucleus solitarius; Obesity; Peripheral; Personal Satisfaction; Pharmaceutical Preparations; Prevention; Property; Public Health; Rat-1; Rattus; Regulation; Reporting; Research; Resistance; Rodent; Role; Safety; Satiation; Signal Pathway; Signal Transduction; Site; Staging; Symptoms; Testing; Therapeutic; Tissues; Toxic effect; Traditional Medicine; Translating; United States; Weight Gain; Work; associated symptom; base; blood glucose regulation; design; fasting glucose; feeding; ginsenoside Rb1; glucose metabolism; impaired glucose tolerance; improved; innovation; insulin secretion; insulin sensitivity; intraperitoneal; leptin receptor; novel; obesity treatment; preclinical study; prevent; reduced food intake; response; targeted agent

DESCRIPTION (provided by applicant): Obesity and type-2 diabetes are national and worldwide epidemics. Since currently available anti-obesity and anti-diabetes drugs have limited efficacy as well as safety concerns, identifying new target compounds, particularly with dual properties in controlling both body weight and blood glucose, is a high priority. Recently, we have identified novel functions of ginsenoside Rb1 (Rb1), the most abundant and biologically active compound in ginseng. Ginseng has been used as a traditional crude medicine in Asian countries to restore and enhance well-being without notable toxic side effects for thousands of years, and is one of the best-selling herbal supplements in the United States. Peripheral administration of Rb1 to rats potently suppresses food intake without eliciting signs of toxicity. Chronic treatment with Rb1 significantly reduces food intake and body weight gain in high-fat diet (HFD)-induced obese rats and also significantly decreases fasting blood glucose and improves impaired glucose tolerance to a greater extent than what occurs in pair-fed controls. These results demonstrate potential novel roles for Rb1 as an anti-obesity and anti-hyperglycemic agent. Our central hypothesis is that Rb1 increases leptin sensitivity to maintain body energy and glucose homeostasis, and it is strongly supported by our preliminary data in lean and HFD-induced obese rats. The rationale for the proposed research is that once the particular mechanisms of Rb1 in the regulation of body weight and blood glucose are understood, the newly acquired information will allow rational design of future pre-clinical studies and clinical trials to develop Rb1 as a novel agent for the prevention and treatment of obesity and diabetes. Guided by strong preliminary data, we propose testing this hypothesis by pursuing three specific aims. First, to determine the interaction of Rb1 and leptin in reducing food intake in rats. Second, to identify the mechanisms through which Rb1 improves energy homeostasis in HFD-induced obese rats. Third, to test the hypothesis that Rb1, like leptin, regulates glucose metabolism by increasing insulin sensitivity at peripheral tissues and/or by increasing insulin secretion. The proposed work is innovative because it assesses novel pharmacological functions of Rb1 in the regulation of energy and glucose homeostasis. Successful completion of the proposed research will enhance our understanding of the mechanisms by which Rb1 prevents and treats obesity and associated symptoms of the metabolic syndrome. Given the continuing epidemics of obesity and diabetes, identifying and understanding a novel pharmacological agent, such as Rb1, with the dual properties of controlling body weight and reducing blood glucose, is expected to have a significant public health impact.

描述（由申请人提供）：肥胖和2型糖尿病是国家和全球流行病。由于目前可用的抗肥胖和抗糖尿病药物具有有限的疗效和安全问题，因此确定新的靶化合物，尤其是在控制体重和血糖的双重特性方面，是一个很高的优先级。最近，我们确定了人参糖苷RB1（RB1）的新功能，它是人参中最丰富和生物活性化合物的新功能。在亚洲国家，人参已被用作传统的原始药物，以恢复和增强福祉，而没有显着的有毒副作用数千年，并且是美国最畅销的草药补品之一。对大鼠的外围施用RB1可有效抑制食物摄入，而不会引起毒性迹象。使用RB1的慢性治疗可显着减少高脂饮食（HFD）诱导的肥胖大鼠的食物摄入和体重增加，并且显着降低了空腹血糖并改善了比配对对照组中发生的葡萄糖耐受性受损的程度。这些结果证明了RB1作为抗肥胖和抗毛血糖剂的潜在新作用。我们的中心假设是，RB1增加了瘦素的敏感性，以维持人体能量和葡萄糖稳态，并且在瘦肉和HFD诱导的肥胖大鼠中的初步数据得到了强有力的支持。拟议研究的理由是，一旦理解RB1在调节体重和血糖中的特定机制，新获得的信息将允许对未来的临床前研究和临床试验进行合理设计，以开发RB1作为预防和治疗肥胖和治疗的新药。在强大的初步数据的指导下，我们提出通过追求三个特定目标来检验这一假设。首先，确定RB1和瘦素在减少大鼠食物摄入量中的相互作用。其次，为了确定RB1改善HFD引起的肥胖大鼠的能量稳态的机制。第三，为了检验RB1，例如瘦素，通过提高胰岛素敏感性和/或增加胰岛素分泌来调节葡萄糖代谢。提出的工作具有创新性，因为它评估了RB1在能量和葡萄糖稳态调节中的新药理功能。成功完成拟议的研究将增强我们对RB1阻止和治疗代谢综合征肥胖和相关症状的机制的理解。鉴于肥胖和糖尿病的持续流行病，鉴定和理解一种新型的药理学剂，例如RB1，具有控制体重和减少血糖的双重特性，预计将对公共卫生产生重大的影响。