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.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AT002445-02
Application #
7033894
Study Section
Special Emphasis Panel (ZAT1-DB (16))
Program Officer
Sorkin, Barbara C
Project Start
2005-04-01
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2008-03-31
Support Year
2
Fiscal Year
2006
Total Cost
$223,374
Indirect Cost
Name
University of Chicago
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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
Luo, Xiaoji; Wang, Chong-Zhi; Chen, Jin et al. (2008) Characterization of gene expression regulated by American ginseng and ginsenoside Rg3 in human colorectal cancer cells. Int J Oncol 32:975-83
Wang, Chong-Zhi; Aung, Han H; Zhang, Bin et al. (2008) Chemopreventive effects of heat-processed Panax quinquefolius root on human breast cancer cells. Anticancer Res 28:2545-51
Wang, Chong-Zhi; Luo, Xiaoji; Zhang, Bin et al. (2007) Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells. Cancer Chemother Pharmacol 60:69-79
Aung, H H; Wang, C Z; Ni, M et al. (2007) Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol 29:175-80
Aung, Han H; Mehendale, Sangeeta R; Wang, Chong Zhi et al. (2007) Cisplatin's tumoricidal effect on human breast carcinoma MCF-7 cells was not attenuated by American ginseng. Cancer Chemother Pharmacol 59:369-74
Xie, J T; Wang, C Z; Ni, M et al. (2007) American ginseng berry juice intake reduces blood glucose and body weight in ob/ob mice. J Food Sci 72:S590-4
Mehendale, Sangeeta; Aung, Han; Wang, Chong-Zhi et al. (2007) Scutellaria baicalensis and a constituent flavonoid, baicalein, attenuate ritonavir-induced gastrointestinal side-effects. J Pharm Pharmacol 59:1567-72
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
Wang, Chong-Zhi; Aung, Han H; Ni, Ming et al. (2007) Red American ginseng: ginsenoside constituents and antiproliferative activities of heat-processed Panax quinquefolius roots. Planta Med 73:669-74

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