ORIGINAL ARTICLE Sangeeta Mehendale Æ Han Aung Æ Anbao Wang Jun-Jie Yin Æ Chong-Zhi Wang Æ Jing-Tian Xie Chun-Su Yuan American ginseng berry extract and ginsenoside Re attenuate cisplatin-induced kaolin intake in rats Received: 9 August 2004 / Accepted: 12 November 2004 / Published online: 25 March 2005 Ó Springer-Verlag 2005 Abstract Purpose: Cisplatin, a chemotherapeutic agent, causes significant nausea and vomiting. It is postulated that cisplatin-induced oxidant stress may be responsi- ble for these symptoms. We tested whether pretreat- ment with American ginseng berry extract (AGBE), an herb with potent antioxidant capacity, and one of its active antioxidant constituents, ginsenoside Re, could counter cisplatin-induced emesis using a rat pica model. Methods: In rats, exposure to emetic stimuli such as cisplatin causes significant kaolin intake, a phenomenon called pica. We therefore measured cis- platin-induced kaolin intake as an indicator of the emetic response. Rats were pretreated with vehicle, AGBE (dose range 50–150 mg/kg, IP) or ginsenoside Re (2 and 5 mg/kg, IP). Rats were treated with cis- platin (3 mg/kg, IP) 30 min later. Kaolin intake, food intake, and body weight were measured every 24 h for 120 h. Additionally, the free radical scavenging activity of AGBE was measured in vitro using ESR spectros- copy. Results: A significant dose-response relationship was observed between increasing doses of pretreatment with AGBE and reduction in cisplatin-induced pica. Kaolin intake was maximally attenuated by AGBE at a dose of 100 mg/kg. Food intake also improved sig- nificantly at this dose (P<0.05). Pretreatment with ginsenoside Re (5 mg/kg) also decreased kaolin intake (P<0.05). In vitro studies demonstrated a concentra- tion-response relationship between AGBE and its ability to scavenge superoxide and hydroxyl radicals. Conclusion: Pretreatment with AGBE and its major constituent, Re, attenuated cisplatin-induced pica, and demonstrated potential for the treatment of chemo- therapy-induced nausea and vomiting. Significant recovery of food intake further strengthens the con- clusion that AGBE may exert an antinausea/antiemetic effect. Keywords American ginseng Æ Berry Æ Ginsenoside Re Æ Herbal medicine Æ Cisplatin Introduction Treatment with cancer chemotherapy and radiotherapy causes unpleasant symptoms such as nausea, vomiting and abdominal discomfort [1–3]. These adverse effects are significant as they cause increased patient morbidity and anticipatory symptoms in the subsequent treatment cycles [1]. The pathophysiology of these symptoms has been partly attributed to oxidant injury to the intestinal epithelium [4, 5]. The mucosal injury results in excessive serotonin release from the enterochromaffin cells that could mediate the gastrointestinal adverse effects of chemotherapy and radiotherapy [6–10]. Since oxidant injury to the gut may be the primary event responsible for the gastrointestinal symptoms following chemo- therapy or radiotherapy, we hypothesized that pre- treatment with an antioxidant should ameliorate these symptoms. S. Mehendale Æ H. Aung Æ A. Wang Æ C.-Z. Wang J.-T. Xie Æ C.-S. Yuan Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 4028, Chicago, IL 60637, USA S. Mehendale Æ H. Aung Æ A. Wang Æ C.-Z. Wang J.-T. Xie Æ C.-S. Yuan Departments of Anesthesia and Critical Care, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA C.-S. Yuan (&) Committee on Clinical Pharmacology and Pharmacogenomics, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA E-mail: cyuan@airway.uchicago.edu Tel.: +1-773-7021916 Fax: +1-773-8340601 J.-J. Yin Center for Food Safety and Applied Nutrition, FDA, College Park, MD, 20740, USA Cancer Chemother Pharmacol (2005) 56: 63–69 DOI 10.1007/s00280-004-0956-1