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

J Transl Med. 2008 Jan 18;6:3. doi: 10.1186/1479-5876-6-3.


Background: We examined the therapeutic potential of a proprietary Croton palanostigma extract (Zangrado(R)) 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 ApcMinmouse model of precancerous adenomatosis polyposis, mice received Zangrado (100 mug/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 ApcMincondition 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiemetics / therapeutic use*
  • Antipruritics / therapeutic use*
  • Cell Line
  • Croton
  • Ferrets
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morphine Derivatives / administration & dosage
  • Nausea / drug therapy
  • Piperidines
  • Plant Extracts / therapeutic use*
  • Proanthocyanidins / therapeutic use*
  • Pruritus / chemically induced
  • Pruritus / drug therapy*
  • Pyrazoles
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Vomiting / chemically induced
  • Vomiting / drug therapy*


  • Antiemetics
  • Antipruritics
  • Morphine Derivatives
  • Piperidines
  • Plant Extracts
  • Proanthocyanidins
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • proanthocyanidin
  • AM 251
  • morphine-6-glucuronide