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.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZAT1-DB (16))
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Sorkin, Barbara C
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University of Chicago
Schools of Medicine
United States
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Wang, Chong-Zhi; Xie, Jing-Tian; Fishbein, Anna et al. (2009) Antiproliferative effects of different plant parts of Panax notoginseng on SW480 human colorectal cancer cells. Phytother Res 23:6-13
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Wang, Chong-Zhi; Xie, Jing-Tian; Zhang, Bin et al. (2007) Chemopreventive effects of Panax notoginseng and its major constituents on SW480 human colorectal cancer cells. Int J Oncol 31:1149-56
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Wang, Chong-Zhi; Mehendale, Sangeeta R; Yuan, Chun-Su (2007) Commonly used antioxidant botanicals: active constituents and their potential role in cardiovascular illness. Am J Chin Med 35:543-58

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