R21 Project: Anti-diabetic Effects of Panax ginseng

糖尿病是一种慢性代谢性疾病，可导致失明、肾衰竭、神经损伤，并增加缺血性心脏病、中风和周围血管疾病的风险。糖尿病分为两大类：1型或胰岛素依赖型糖尿病（IDDM）和2型或非胰岛素依赖型糖尿病（NIDDM）。在这个国家，糖尿病的发病率约为4.5%，其中90%是2型糖尿病。1992年，美国医疗保健总支出（1050亿美元）中约有14.6%用于治疗糖尿病。这些患者中的许多人还患有糖尿病并发症。考虑到这种疾病的异质性，以及现有治疗方法的局限性，如继发性失败率高和副作用，迫切需要探索新的抗糖尿病药物。本研究项目与补充和替代医学领域有用产品的开发有关。本课题将重点研究人参的抗糖尿病作用，是我们前期人参药理研究的延续。最近，在我们的初步研究中，我们观察到使用人参浆果（或水果）提取物，而不是常用的人参根提取物，对ob/ob小鼠的抗糖尿病作用有令人兴奋的结果。ob/ob小鼠是2型糖尿病的遗传模型，这些动物具有极强的胰岛素抵抗性，空腹血糖水平明显高于瘦小鼠。我们的初步观察数据显示，人参浆果提取物使ob/ob小鼠的高血糖正常化，并增加胰岛素敏感性。此外，我们还通过高效液相色谱法分析了人参浆果的成分，发现与人参根相比，人参浆果具有独特的人参皂苷，人参皂苷是人参的重要成分。在这个修改的提案中，我们将检验人参浆果提取物具有显著的抗高血糖活性的假设。本项目旨在鉴定人参莓的抗高血糖成分，以及这些成分之间的协同作用。我们还将研究这些活性成分的作用机制。我们的策略是使用ob/ob小鼠，使用体内引导的化学分离方法从人参浆果中分离出纯净的，具有生物活性的抗高血糖化合物。葡萄糖稳态、葡萄糖耐量和体内胰岛素敏感性的改善将被测试。拟议项目的结果也将有助于在治疗剂开发之前填补我们的知识空白。

Diabetes mellitus or diabetes is a chronic metabolic disease that can cause blindness, kidney failure, nerve damage, and confers an increased risk of ischemic heart disease, stroke and peripheral vascular disease. Diabetes is divided into two major categories: type 1 or insulin- dependent diabetes mellitus (IDDM), and type 2 or non-insulin dependent diabetes mellitus (NIDDM). In this country, the incidence of diabetes is approximately 4.5%, of which 90% is type 2 diabetes. In 1992, diabetes care required roughly 14.6% of the total U.S. health care expenditure ($105 billion). Many of these patients also suffer from diabetic complications. Considering the heterogeneity of this disease, and the limitations of current therapies, such as high secondary failure rates and side effects, there is an urgent need to explore new anti- diabetic agents. This research project is related to the development of useful products in the field of complementary and alternative medicine. This proposal will focus on our studies on anti-diabetic effects of Panax ginseng, and this project is a continuation of our previous ginseng pharmacological studies. Recently, in our preliminary studies, we observed exciting results on anti-diabetic actions in ob/ob mice using Panax ginseng berry (or fruit) extract, other than the commonly used root extract. The ob/ob mice is a genetic model for type 2 diabetes, and these animals are extremely insulin resistant and have fasting blood glucose levels that are significantly higher than that of lean mice. Data from our pilot observation showed that extract of Panax ginseng berry normalized hyperglycemia and increased insulin sensitivity in ob/ob mice. In addition, we analyzed the constituents of the ginseng berry by HPLC analysis and found that, compared to ginseng root, the ginseng berry has a distinctive profile of ginsenosides, the vital constituent of ginseng. In this revised proposal, we will test the hypothesis that Panax ginseng berry extract has significant anti-hyperglycemic activity. The project aims to identify the anti-hyperglycemic constituents of Panax ginseng berry, and synergistic effects between these constituents. We will also investigate mechanisms of action of these active component(s). Our strategy is to use an in vivo-guided chemical fractionation method to isolate the pure, biologically active, anti-hyperglycemic compound(s) from Panax ginseng berry using the ob/ob mouse. Improvements in glucose homeostasis, glucose tolerance, and in vivo insulin sensitivity will be tested. The results of the proposed project will also help fill gaps in our knowledge before therapeutic agents can be developed.