CARDIOPROTECTIVE EFFECTS OF AMERICAN GINSENG

描述（由申请人提供）：患有心血管疾病的患者经常使用草药作为常规药物治疗的低成本替代品。西洋参是一种非常常见的心血管疾病草药，它是一种公认的抗氧化剂。由于氧化剂介导的损伤是急性和慢性心功能不全的已知机制，因此这些草药可以通过减轻氧化剂损伤来提供心脏保护作用。活性氧（ROS）在两种不同的情况下产生：在诸如缺血/再灌注（I/R）的条件下的急性氧化剂释放和在若干生物过程中作为信号分子的ROS产生。 我们建议研究西洋参的抗氧化作用，这可能会影响ROS的这些不同的作用。在急性氧化应激条件下，ROS从心肌细胞内的几个部位迅速产生，导致细胞成分损伤、功能障碍和细胞死亡。 只有当外源性抗氧化剂快速进入ROS产生的部位时，才能显著改善对这种损伤的有效保护。由于西洋参含有活性成分（西洋参皂苷），这些活性成分具有允许快速进入细胞的化学结构，西洋参皂苷可以抑制自由基，从而保护免受急性氧化应激。 西洋参还可以与心肌细胞内释放的ROS相互作用，作为响应各种病理生理刺激的信号分子。具体目标1将研究西洋参在小鼠心肌细胞中模拟I/R产生ROS时的保护作用，具体目标2将研究西洋参在减弱响应各种刺激释放的ROS方面的作用，以及如何改变对氧化还原依赖过程的生物反应。此外，将比较从西洋参植物的两个部分：根和浆果获得的提取物的抗氧化作用。由于根提取物和浆果提取物的抗氧化特性显著不同，我们预计抗氧化潜力也不同。我们的研究结果表明西洋参提取物具有治疗心血管疾病的潜力。

DESCRIPTION (provided by applicant): Patients suffering from cardiovascular disease frequently use herbal medicines as a low-cost alternative to conventional, pharmacological treatment. American ginseng is a very commonly consumed herbal remedy for cardiovascular conditions and it is a putative antioxidant. Since oxidant-mediated injury is a known mechanism of acute and chronic cardiac dysfunction, these herbs could offer cardioprotective effects through attenuation of oxidant injury. Reactive oxygen species (ROS) are generated in two distinct scenarios: acute oxidant release in conditions such as ischemia/reperfusion (I/R) and ROS generation as signaling molecules in several biological processes. We propose to study the antioxidant effects of American ginseng, which could affect both these distinct roles of ROS. During conditions of acute oxidant stress, ROS are generated rapidly from several sites within the cardiomyocyte, resulting in injury to cellular constituents, dysfunction and cell death. Effective protection against such injury can be significantly improved only if exogenously administered antioxidants rapidly access the site of ROS generation. Since American ginseng contains active constituents (ginsenosides) that are endowed with chemical structures that allow rapid entry in the cells, the ginsenosides could scavenge free radicals resulting in protection against acute oxidant stress. American ginseng could also interact with ROS released within cardiomyocytes as signaling molecules in response to a variety of pathophysiological stimuli. Specific Aim 1 will study the protective effect of American ginseng when ROS are generated by simulated I/R in mouse cardiomyocytes, and Specific Aim 2 will examine American ginseng effects in attenuating ROS released in response to various stimuli and how the biological responses to redox-dependent processes are altered. Additionally, the antioxiant effects of extracts obtained from two parts of the American ginseng plant: the root and berry will be compared. Since the ginsenoside profile of the root extract and the berry extract differs significantly, we expect the antioxidant potential to differ. Our results could show that American ginseng extracts have a potential in treating cardiovascular disease.