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


CONCLUSIONS
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.
Miller
Mark J S
MJ
Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA. markjsm03@yahoo.com
Reuter
Brian K
BK
Wallace
John L
JL
Sharkey
Keith A
KA
D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use*; D000982:Antipruritics / Q000627:therapeutic use*; D002460:Cell Line; D029802:Croton; D005289:Ferrets; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009022:Morphine Derivatives / Q000008:administration & dosage; D009325:Nausea / Q000188:drug therapy; D010880:Piperidines; D010936:Plant Extracts / Q000627:therapeutic use*; D044945:Proanthocyanidins / Q000627:therapeutic use*; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy*; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
D000932:Antiemetics; D000982:Antipruritics; D009022:Morphine Derivatives; D010880:Piperidines; D010936:Plant Extracts; D044945:Proanthocyanidins; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C013221:proanthocyanidin; C103505:AM 251; C035349:morphine-6-glucuronide