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: 8295114
• 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 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8295114
• 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; Diet; Dose; Eating; Epidemic; FOS gene; Fasting; Fatty acid glycerol esters; Future; Ginseng Preparation; 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; 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; response

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. PUBLIC HEALTH RELEVANCE: The objective of this project is to elucidate the mechanisms by which the compound Rb1 prevents and treats obesity, diabetes and other symptoms of the metabolic syndrome. Given the growing incidence of obesity and diabetes, identifying and understanding a new pharmacological agent, like Rb1, with 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型糖尿病是国家和世界范围的流行病。由于目前可用的抗肥胖和抗糖尿病药物具有有限的功效以及安全性问题，因此鉴定新的目标化合物，特别是具有控制体重和血糖的双重性质的目标化合物是高度优先的。最近，我们已经确定了人参中最丰富和最具生物活性的化合物Rb 1（Rb 1）的新功能。几千年来，人参一直被用作亚洲国家的传统生药，以恢复和增强健康，而没有明显的毒副作用，并且是美国最畅销的草药补充剂之一。大鼠外周给予Rb 1可有效抑制食物摄入，而不会引起毒性体征。长期治疗与Rb 1显着减少食物摄入量和体重增加高脂饮食（HFD）诱导的肥胖大鼠，也显着降低空腹血糖和改善葡萄糖耐量受损的程度比发生在配对喂养的控制。这些结果表明Rb 1作为抗肥胖和抗高血糖剂的潜在新作用。我们的中心假设是，Rb 1增加瘦素的敏感性，以维持身体能量和葡萄糖的稳态，这是强烈支持我们的初步数据在瘦和HFD诱导的肥胖大鼠。这项研究的基本原理是，一旦了解了Rb 1调节体重和血糖的特定机制，新获得的信息将允许合理设计未来的临床前研究和临床试验，以开发Rb 1作为预防和治疗肥胖和糖尿病的新型药物。在强有力的初步数据的指导下，我们提出通过追求三个具体目标来检验这一假设。首先，确定Rb 1和瘦素在减少大鼠摄食量中的相互作用。第二，确定Rb 1改善HFD诱导的肥胖大鼠能量稳态的机制。第三，检验Rb 1和瘦素一样，通过增加外周组织的胰岛素敏感性和/或通过增加胰岛素分泌来调节葡萄糖代谢的假设。这项工作是创新的，因为它评估了Rb 1在调节能量和葡萄糖稳态方面的新药理学功能。成功完成拟议的研究将提高我们对Rb 1预防和治疗肥胖和代谢综合征相关症状的机制的理解。鉴于肥胖症和糖尿病的持续流行，识别和理解具有控制体重和降低血糖双重特性的新型药理学试剂，如Rb 1，预计将对公共卫生产生重大影响。 公共卫生相关性：该项目的目的是阐明化合物Rb 1预防和治疗肥胖、糖尿病和代谢综合征的其他症状的机制。鉴于肥胖和糖尿病的发病率不断增加，识别和了解一种新的药理学药物，如Rb 1，具有控制体重和降低血糖的双重特性，预计将对公共卫生产生重大影响。