EFFECT OF GINSENG ON CISPLATIN-INDUCED EMESIS

描述（由申请人提供）：使用顺铂等血液治疗药物治疗癌症具有严重的不良反应，不仅会使患者的生活质量恶化，而且可能导致他们拒绝可能治愈的化疗。恶心/呕吐是化疗药物的一个重要不良反应，应适当控制，以减少发病率，提高化疗的有效性。目前可用的止吐药物可缓解症状，特别是在联合使用时，但可能导致额外的药物相关不良事件和药物-药物相互作用。顺铂诱导的胃排空延迟也可能有助于恶心/呕吐的发病机制。引起胃肠道病理的种子事件可能是由肠道氧化损伤过程中释放的神经递质引起的。因此，我们建议使用一种草药抗氧化剂，西洋参，拮抗氧化事件，并确定其治疗顺铂诱导的呕吐的潜力。我们将在大鼠模型中研究西洋参根提取物（AGRE）和西洋参浆果提取物（AGBE）及其有效成分（人参皂苷Rg1， Rb1， Re和Rd）在减少化疗诱导的恶心/呕吐和改善胃排空中的作用。大鼠对顺铂等催吐刺激物的反应是改变摄食习惯，表现为对高岭土（一种粘土）等非营养性物质的消耗增加，即异食癖。顺铂诱导高岭土消耗显著增加，该大鼠模型已用于评估新型止吐化合物。此外，顺铂还能延缓大鼠胃排空。我们假设给予AGRE、AGBE及其有效成分将有效减少异食癖和改善胃排空，同时保留顺铂的杀肿瘤活性。在本研究中，我们将评估AGRE、AGBE和人参皂苷Rg1、Rb1、Re和Rd在顺铂治疗大鼠中的止吐活性，并确定中药对顺铂杀瘤活性的影响。由于西洋参对其他组织的化疗药物具有杀瘤和抗氧化保护作用，我们预计西洋参将成为癌症化疗中有效的止吐药物。

DESCRIPTION (provided by applicant): Treatment of cancer with hemotherapeutic agents such as cisplatin is associated with severe adverse effects that not only worsen patients' quality of life but also could lead to their refusal of potentially curative chemotherapy. Nausea/vomiting, a significant adverse effect of chemotherapeutic drugs, should be adequately controlled to reduce morbidity and improve effectiveness of chemotherapy. The currently available anti-emetic drugs relieve the symptoms especially when used in combinations, but lead to the possibility of additional drug-related adverse events and drug-drug interactions. Cisplatin-induced delayed gastric emptying could also contribute to the pathogenesis of nausea/vomiting. The seminal event that causes the gastrointestinal pathology is likely caused by neurotransmitters released during oxidant injury to the gut. We therefore propose to use an herbal anti-oxidant, American ginseng, to antagonize the oxidant events and to determine it's potential in treating cisplatin-induced emesis. We will investigate the role of American ginseng root extract (AGRE) and American ginseng berry extract (AGBE), and their active constituents (ginsenosides Rg1, Rb1, Re, and Rd ), in reducing chemotherapy-induced nausea/vomiting and in improving gastric emptying in a rat model. Rats react to emetic stimuli, like cisplatin, by altered feeding habits, manifested as increased consumption of non-nutritive substances like kaolin (a type of clay), known as pica. Cisplatin induces a significant increase in kaolin consumption, and this rat model has been utilized to evaluate novel anti-emetic compounds. In addition, cisplatin also delays gastric emptying in rats. We hypothesize that administration of AGRE, AGBE and their active constituents will effectively reduce pica and improve gastric emptying, while preserving the tumoricidal activity of cisplatin. In the proposed study, we will evaluate anti-emetic activities of AGRE, AGBE and ginsenosides Rg1, Rb1, Re, and Rd in rats treated with cisplatin, and determine herbal effects on the tumoricidal activity of cisplatin. Due to the fact that ginseng has shown tumoricidal properties and antioxidant protection from chemotherapeutic agents in other tissues, we expect that American ginseng will be an efficacious anti-emetic treatment in cancer chemotherapy.