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

Miller MJ, Reuter BK, Wallace JL, Sharkey KA - J Transl Med (2008)

Bottom Line: These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism.Zangrado did not exacerbate the ApcMincondition rather health was improved.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA. markjsm03@yahoo.com

ABSTRACT

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.

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Related in: MedlinePlus

Suppression of morphine-6-glucuronide-induced vomiting and retching in ferrets with Zangrado, and the effects of CB1 receptor antagonism with AM 251. Ferrets treated with the opioid narcotic, morphine-6-glucuronide (M6G) display a substantial emetic response with on average over 12 episodes per hour. Zangrado administration (3 mg/kg ip) 15 minutes prior to M6G resulted in a 77% reduction in emetic episodes (n = 6, P < 0.01). Co-administration of Zangrado with the CB receptor antagonist, AM 251 (5 mg/kg, ip) failed to reverse the anti-emetic effects of Zangrado (n = 6). The slight increase in emetic episodes with AM 251 is comparable to that seen with ferrets treated with AM 251 alone and is thought to reflect the anti-emetic effects of endogenous cannabinoids [20,21].
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Figure 1: Suppression of morphine-6-glucuronide-induced vomiting and retching in ferrets with Zangrado, and the effects of CB1 receptor antagonism with AM 251. Ferrets treated with the opioid narcotic, morphine-6-glucuronide (M6G) display a substantial emetic response with on average over 12 episodes per hour. Zangrado administration (3 mg/kg ip) 15 minutes prior to M6G resulted in a 77% reduction in emetic episodes (n = 6, P < 0.01). Co-administration of Zangrado with the CB receptor antagonist, AM 251 (5 mg/kg, ip) failed to reverse the anti-emetic effects of Zangrado (n = 6). The slight increase in emetic episodes with AM 251 is comparable to that seen with ferrets treated with AM 251 alone and is thought to reflect the anti-emetic effects of endogenous cannabinoids [20,21].

Mentions: Ferrets respond to M6G with a rapid and reproducible emetic response (vomiting and retching) that typically abates within 10 minutes. Previously, we have shown that this response is suppressed by CB1 receptor agonism and enhanced by CB1 receptor antagonism [20,21]. At the dose of 3 mg/kg, Zangrado was a remarkably effective anti-emetic reducing episodes of vomiting and retching in M6G treated ferrets by 77% (Figure 1). Co-administration of the CB1 receptor antagonist, AM 251, failed to reverse this response, although the number of episodes did increase. However, the magnitude of this AM 251 effect was comparable to what we have previously observed in the M6G model with AM 251 in the absence of Zangrado. In other words, AM 251 significantly raises emetic episodes in M6G treated ferrets because it blocks the anti-emetic tone exerted of endogenous cannabinoids [20]. The number of licking episodes, was reduced by 87% with Zangrado (Fig. 2). This effect was not reversed by AM 251.


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

Miller MJ, Reuter BK, Wallace JL, Sharkey KA - J Transl Med (2008)

Suppression of morphine-6-glucuronide-induced vomiting and retching in ferrets with Zangrado, and the effects of CB1 receptor antagonism with AM 251. Ferrets treated with the opioid narcotic, morphine-6-glucuronide (M6G) display a substantial emetic response with on average over 12 episodes per hour. Zangrado administration (3 mg/kg ip) 15 minutes prior to M6G resulted in a 77% reduction in emetic episodes (n = 6, P < 0.01). Co-administration of Zangrado with the CB receptor antagonist, AM 251 (5 mg/kg, ip) failed to reverse the anti-emetic effects of Zangrado (n = 6). The slight increase in emetic episodes with AM 251 is comparable to that seen with ferrets treated with AM 251 alone and is thought to reflect the anti-emetic effects of endogenous cannabinoids [20,21].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2254379&req=5

Figure 1: Suppression of morphine-6-glucuronide-induced vomiting and retching in ferrets with Zangrado, and the effects of CB1 receptor antagonism with AM 251. Ferrets treated with the opioid narcotic, morphine-6-glucuronide (M6G) display a substantial emetic response with on average over 12 episodes per hour. Zangrado administration (3 mg/kg ip) 15 minutes prior to M6G resulted in a 77% reduction in emetic episodes (n = 6, P < 0.01). Co-administration of Zangrado with the CB receptor antagonist, AM 251 (5 mg/kg, ip) failed to reverse the anti-emetic effects of Zangrado (n = 6). The slight increase in emetic episodes with AM 251 is comparable to that seen with ferrets treated with AM 251 alone and is thought to reflect the anti-emetic effects of endogenous cannabinoids [20,21].
Mentions: Ferrets respond to M6G with a rapid and reproducible emetic response (vomiting and retching) that typically abates within 10 minutes. Previously, we have shown that this response is suppressed by CB1 receptor agonism and enhanced by CB1 receptor antagonism [20,21]. At the dose of 3 mg/kg, Zangrado was a remarkably effective anti-emetic reducing episodes of vomiting and retching in M6G treated ferrets by 77% (Figure 1). Co-administration of the CB1 receptor antagonist, AM 251, failed to reverse this response, although the number of episodes did increase. However, the magnitude of this AM 251 effect was comparable to what we have previously observed in the M6G model with AM 251 in the absence of Zangrado. In other words, AM 251 significantly raises emetic episodes in M6G treated ferrets because it blocks the anti-emetic tone exerted of endogenous cannabinoids [20]. The number of licking episodes, was reduced by 87% with Zangrado (Fig. 2). This effect was not reversed by AM 251.

Bottom Line: These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism.Zangrado did not exacerbate the ApcMincondition rather health was improved.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA. markjsm03@yahoo.com

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus