Research

A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient

Mark JS Miller¹ , Brian K Reuter² , John L Wallace³ and Keith A Sharkey⁴

¹Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA

²Department of Medicine, University of Virginia, Charlottesville, Virginia, USA

³Inflammation Research Network, Department of Pharmacology and Experimental Therapeutics, University of Calgary, Alberta, Canada

⁴Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada

author email corresponding author email

Journal of Translational Medicine 2008, 6:3doi:10.1186/1479-5876-6-3

Published:	18 January 2008

Abstract

Background

We examined the therapeutic potential of a proprietary Croton palanostigma extract (Zangrado^®) in the management of emesis and itch.

Methods

Emesis was induced in ferrets with morphine-6-glucuronide (0.05 mg/kg sc) in the presence of Zangrado (3 mg/kg, ip) and the cannabinoid receptor 1 antagonist, AM 251 (5 mg/kg, ip). Topical Zangrado (1%) was assessed for anti-pruretic actions in the 5-HT-induced scratching model in rats and evaluated in capsaicin-induced gastric hyperemia as measured by laser doppler flow. In the Apc^Minmouse model of precancerous adenomatosis polyposis, mice received Zangrado (100 μg/ml in drinking water) from the age of 6 – 16 weeks for effects on polyp number. In RAW 264.7 cells Zangrado was examined for effects on lipopolysaccharide-induced nitrite production.

Results

Zangrado was a highly effective anti-emetic, reducing morphine-induced vomiting and retching by 77%. These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism. Itch responses were blocked in both the morphine and 5-HT models. Zangrado did not exacerbate the Apc^Mincondition rather health was improved. Capsaicin-induced hyperemia was blocked by Zangrado, which also attenuated the production of nitric oxide by activated macrophages.

Conclusion

Zangrado is an effective anti-emetic and anti-itch therapy that is devoid of common side-effects, cannabinoid-independent and broadly suppresses sensory afferent nerve activation. This complementary medicine represents a promising new approach to the management of nausea, itch and irritable bowel syndrome.