Zangrado® and Progrado® - Benefits

Zangrado® & Progrado® -  Patented, Highly Concentrated Substances:
(Support studies listed in the Scientific Studies section) 

Zangrado® and Zangrado® are patented extracts derived from the viscous red latex of the Croton species tree found primarily in the South American rainforests and is sustainably wild-crafted. RNI original research demonstrated their mechanism of action as regulating the sensory afferent neurons that line the internal organs as well as the skin

  • Powerful Proanthocyanidins  

  • Powerful Antioxidant Properties

Both extracts affect over-stimulated sensory neurons and signal the central nervous system to respond. Orally, both Progrado and Zangrado have been effective in the treatment of nausea and ulcers with implications for irritable bowel syndrome and gastroesophageal reflux disease as well as other gastrointestinal complaints. Topically, Zangrado has been shown clinically effective in reducing pain and itching associated with insect bites and stings, contact dermatitis, and plays a cicatrizing role in the healing process.

Sensory (afferent) neurons are nerves that respond to sensation – such as pain and itch – and are located throughout the body – lining the skin, organs and lungs.  In a sense, coughing is your body’s way of “itching” its lungs.

Additionally, in human cells, Progrado has been shown to regulate overactive matrix metalloproteinases, molecular “scissors” from breaking down cartilage while increasing cellular IGF-1 levels.  

Zangrado® has been used in clinical trials topically to treat the pain and itch associated with bug bites and bee stings. It has been used internally to reduce nausea (emesis), diarrhea and also itch. Coughing is a method the lungs use to “itch” themselves so intuitively, Zangrado® would be effective internally for certain respiratory conditions. Progrado® has been shown to affect matrix metalloproteinase (MMPs). These are the molecular “scissors” that breakdown cartilage which is normally replaced by new cells.

Progrado® thus allows the body to repair itself.

Importantly, as with red wine, the proanthocyanidins found in Progrado® may offer benefits to the cardiovascular system.

Zangrado® and Progrado® - Science

Ingredient: Zangrado® and Progrado® - Works Cited:

(1) Chordia P, MacArthur RD: Crofelemer, a novel agent for treatment of noninfectious diarrhea in HIV-infected persons. Expert Rev Gastroenterol Hepatol. 2013 Sep;7(7):591-600. http://www.ncbi.nlm.nih.gov/pubmed/24070150

(2) Alonso-Castro AJ, Domínguez F, García-Carrancá A: Rutin exerts antitumor effects on nude mice bearing SW480 tumor. Arch Med Res. 2013 Jul;44(5):346-51. http://www.ncbi.nlm.nih.gov/pubmed/23867787

(3) Frampton JE: Crofelemer: a review of its use in the management of noninfectious diarrhoea in adult patients with HIV/AIDS on antiretroviral therapy. Drugs. 2013 Jul;73(10):1121-9 http://www.ncbi.nlm.nih.gov/pubmed/23807722

(4) Rossi D, Guerrini A, Paganetto G et al: Croton lechleri Müll. Arg. (Euphorbiaceae) stem bark essential oil as possible mutagen-protective food ingredient against heterocyclic amines from cooked food. Food Chem. 2013 Aug 15;139(1-4):439-47. http://www.ncbi.nlm.nih.gov/pubmed/23561129

(5) Montopoli M, Bertin R, Chen Z et al: Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against human melanoma SK23 and colon cancer HT29 cell lines. J Ethnopharmacol. 2012 Dec 18;144(3):747-53. http://www.ncbi.nlm.nih.gov/pubmed/23123266

(6) Alonso-Castro AJ, Ortiz-Sánchez E, Domínguez F et al: Antitumor effect of Croton lechleri Mull. Arg. (Euphorbiaceae). J Ethnopharmacol. 2012 Mar 27;140(2):438-42. http://www.ncbi.nlm.nih.gov/pubmed/22301443

(7) Cottreau J, Tucker A, Crutchley R et al: Crofelemer for the treatment of secretory diarrhea. Expert Rev Gastroenterol Hepatol. 2012 Feb;6(1):17-23. http://www.ncbi.nlm.nih.gov/pubmed/22301443

(8) Pereira U, Garcia-Le Gal C, Le Gal G et al: Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation. Exp Dermatol. 2010 Sep;19(9):796-9. http://www.ncbi.nlm.nih.gov/pubmed/20698880

(9) Takami Y, Uto H, Takeshita M et al: Proanthocyanidin derived from the leaves of Vaccinium virgatum suppresses platelet-derived growth factorinduced proliferation of the human hepatic stellate cell line LI90. Hepatol Res. 2010 Apr;40(4):337-45. http://www.ncbi.nlm.nih.gov/pubmed/20070402

(10) Tradtrantip L, Namkung W, Verkman AS: Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. http://www.ncbi.nlm.nih.gov/pubmed/19808995

(11) Fayad W, Fryknäs M, Brnjic S et al: Identification of a novel topoisomerase inhibitor effective in cells overexpressing drug efflux transporters. PLoS One. 2009 Oct 2;4(10):e7238. http://www.ncbi.nlm.nih.gov/pubmed/19798419

(12) Froldi G, Zagotto G, Filippini R et al: Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles. Phytomedicine. 2009 Aug;16(8):768-75. http://www.ncbi.nlm.nih.gov/pubmed/19406630

(13) Miller MJ, Reuter BK, Wallace JL et al: A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient. J Transl Med. 2008 Jan 18;6:3. http://www.ncbi.nlm.nih.gov/pubmed/18205911

(14) De Marino S, Gala F, Zollo F et al: Identification of minor secondary metabolites from the latex of Croton lechleri (Muell-Arg) and evaluation of their antioxidant activity. Molecules. 2008 Jun 1;13(6):1219-29. http://www.ncbi.nlm.nih.gov/pubmed/18596648

(15) Miller MJ, Bobrowski P, Shukla M et al: Chondroprotective effects of a proanthocyanidin rich Amazonian genonutrient reflects direct inhibition of matrix metalloproteinases and upregulation of IGF-1 production by human chondrocytes. J Inflamm (Lond). 2007 Aug 14;4:16. http://www.ncbi.nlm.nih.gov/pubmed/17697350

(16) Tran CD, Butler RN, Miller MJ: The role of Amazonian herbal medicine Sangre de Grado in Helicobacter pylori infection and its association with metallothionein expression. Helicobacter. 2006 Apr;11(2):134-5. http://www.ncbi.nlm.nih.gov/pubmed/16579844

(17) Gonzales GF, Valerio LG Jr: Medicinal plants from Peru: a review of plants as potential agents against cancer. Anticancer Agents Med Chem. 2006 Sep;6(5):429-44. Review. http://www.ncbi.nlm.nih.gov/pubmed/17017852

(18) Miller MJS, Reuter BK, Bobrowski PJ et al (1996): “Mechanistic and Clinical Assessment of Zangrado®, an Extract of the Amazonian Ethnomedicine Sangre de Grado, for the Treatment of Itch” In Gil Yosipovitch, Malcolm W. Greaves, Alan B. Fleischer, Jr & Francis McGlone (Editors) Itch: Basic Mechanisms and Therapy (pp. 305-315). New York: Marcel Dekker. http://books.google.com/books?id=SzATlwEACAAJ&dq=miller+reuter+bobrowski+Itch&hl=en&sa=X&ei=12EXVJakIeW88QHozYEQ&ved=0CCoQ6AEwAg

 (19) Lopes MI, Saffi J, Echeverrigaray S et al: Mutagenic and antioxidant activities of Croton lechleri sap in biological systems. J Ethnopharmacol. 2004 Dec;95(2-3):437-45. http://www.ncbi.nlm.nih.gov/pubmed/15507372

(20) Fischer H, Machen TE, Widdicombe JH et al: A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells. J Ethnopharmacol. 2004 Aug;93(2- 3):351-7. http://www.ncbi.nlm.nih.gov/pubmed/15234776

(21) Jones K: Review of sangre de drago (Croton lechleri)--a South American tree sap in the treatment of diarrhea, inflammation, insect bites, viral infections, and wounds: traditional uses to clinical research. J Altern Complement Med. 2003 Dec;9(6):877-96. Review. http://www.ncbi.nlm.nih.gov/pubmed/14736360

(22) Risco E, Ghia F, Vila R et al: Immunomodulatory activity and chemical characterisation of sangre de drago (dragon's blood) from Croton lechleri. Planta Med. 2003 Sep;69(9):785-94. http://www.ncbi.nlm.nih.gov/pubmed/14598201

(23) Rossi D, Bruni R, Bianchi N et al: Evaluation of the mutagenic, antimutagenic and antiproliferative potential of Croton lechleri (Muell. Arg.) latex. Phytomedicine. 2003 Mar;10(2-3):139-44. http://www.ncbi.nlm.nih.gov/pubmed/12725567

(24) Sandoval M, Okuhama NN, Clark M et al: Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells. J Ethnopharmacol. 2002 May;80(2-3):121-9. http://www.ncbi.nlm.nih.gov/pubmed/12007701

(25) Williams JE: Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado. Altern Med Rev. 2001 Dec;6(6):567-79. Review. http://www.ncbi.nlm.nih.gov/pubmed/11804547

(26) Miller MJ, Vergnolle N, McKnight W et al: Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado. J Invest Dermatol. 2001 Sep;117(3):725-30. http://www.ncbi.nlm.nih.gov/pubmed/11564183

(27) Miller MJ, MacNaughton WK, Zhang XJ et al: Treatment of gastric ulcers and diarrhea with the Amazonian herbal medicine sangre de grado. Am J Physiol Gastrointest Liver Physiol. 2000 Jul;279(1):G192-200. http://www.ncbi.nlm.nih.gov/pubmed/10898763

(28) Desmarchelier C, Witting Schaus F, Coussio J et al: Effects of Sangre de Drago from Croton lechleri Muell.-Arg. on the production of active oxygen radicals. J Ethnopharmacol. 1997 Oct;58(2):103-8. http://www.ncbi.nlm.nih.gov/pubmed/9406898

(29) Pieters L, De Bruyne T, Van Poel B et al: In vivo wound healing activity of Dragon's Blood (Croton spp.), a traditional South American drug, and its constituents. Phytomedicine. 1995 Jul;2(1):17-22. http://www.ncbi.nlm.nih.gov/pubmed/23196095

(30) Phillipson JD: A matter of some sensitivity. Phytochemistry. 1995 Apr;38(6):1319-43. Review. http://www.ncbi.nlm.nih.gov/pubmed/7786474 

(31) Chen ZP, Cai Y, Phillipson JD: Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon's blood. Planta Med. 1994 Dec;60(6):541-5. http://www.ncbi.nlm.nih.gov/pubmed/7809208

(32) Ubillas R, Jolad SD, Bruening RC et al: SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago). Phytomedicine. 1994 Sep;1(2):77-106. http://www.ncbi.nlm.nih.gov/pubmed/23195881

(33) Pieters L, de Bruyne T, Claeys M et al: Isolation of a dihydrobenzofuran lignan from South American dragon's blood (Croton spp.) as an inhibitor of cell proliferation. J Nat Prod. 1993 Jun;56(6):899-906. http://www.ncbi.nlm.nih.gov/pubmed/8350090

 (34) Itokawa H, Ichihara Y, Mochizuki M et al: A cytotoxic substance from Sangre de Grado. Chem Pharm Bull (Tokyo). 1991 Apr;39(4):1041-2. http://www.ncbi.nlm.nih.gov/pubmed/1893488

(35) Vaisberg AJ, Milla M, Planas MC et al: Taspine is the cicatrizant principle in Sangre de Grado extracted from Croton lechleri. Planta Med. 1989 Apr;55(2):140-3. http://www.ncbi.nlm.nih.gov/pubmed/2748730

(36) Perdue GP, Blomster RN, Blake DA et al: South American plants II: taspine isolation and anti-inflammatory activity. J Pharm Sci. 1979 Jan;68(1):124-6. http://www.ncbi.nlm.nih.gov/pubmed/758452

(37) Rozhon EJ et al: Compositions and methods of treatment with proanthocyanidin polymer antidiarrheal compositions. USPTO 8,574,634:

Nov 5, 2013. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=3&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(38) Quart BD et al: Method for treatment of constipation-predominant irritable bowel syndrome. USPTO 8,067,041: Nov 29, 2011. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=13&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(39) Bobrowski PJ: Method of treating emesis and itch. USPTO 7,883,727: Feb 8, 2011. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=15&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(40) Quart BD et al: Method for treatment of constipation-predominant irritable bowel syndrome. USPTO 7,556,83. Jul 7, 2009. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=25&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(41) Rozhon EJ et al: Method of treating secretory diarrhea with enteric formulations of proanthocyanidin polymer. USPTO 7,341,744: Mar 11, 2008. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=27&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(42) Rozhon EJ et al: Enteric formulations of proanthocyanidin polymer antidiarrheal compositions. USPTO 7,323,195; Jan 29, 2008. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=28&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(43) Bobrowski PJ: Methods and preparations of the latex from the croton species. USPTO 7,208,183: Apr 24, 2007. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=30&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(44) Tempesta MS: Methods for using proanthocyanidin polymers having antiviral activity. USPTO 5,494,661: Feb 27, 1996. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=32&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(45) Winter REK et al: Wound-healing composition and method. USPTO 5,474,782: Dec 12, 1995. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.tml&r=33&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(46) Tempesta M: Proanthocyanidin polymers having antiviral activity and methods of obtaining same. USPTO 5,211,944: May 18, 1993. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=34&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

(47) Lewis WH et al: Wound-healing composition. USPTO 5,156,847: Oct 20, 1992. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=35&f=http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearchbool.html&r=35&f=G&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri&l=50&co1=AND&d=PTXT&s1=Croton&s2=lechleri&OS=Croton+AND+lechleri&RS=Croton+AND+lechleri

Additional Studies: 

  1. Bobrowski, PJ: Methods and preparations of the latex from the croton species. USPTO No. 7,208,183. 2007 April 24.

  2. Bobrowski PJ: Pharmaceutical preparations for the treatment of itch, nausea, hyperalgesia and the complications of opioid agonists.  USPTO No. 7,632,524. 2009 Dec 15.

  3. Bobrowski PJ: Method of treating emesis and itch.  USPTO No. 7,883,727.  2011 Feb 8, 2011.

  4. Miller M, Macnaughton W, Zhang X et al: Treatment of gastric ulcers and diarrhea with the Amazonian herbal medicine sangre de grado. Am J Physio Gastro Liver Physiology, 2000, 279: G192–G200. 

  5. Miller M, Vergnolle N, McKnight W et al: Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado. Journal of Investigative Dermatology, 2001, 117(3): 725-730. 

  6. Miller M, Reuter B, Wallace J, Sharkey K, Bobrowski P: Mechanistic and Clinical Assessment of Zangrado, an Extract of the Amazonian Ethnomedicine Sangre de Grado, for the Treatment of Itch.  In: Yosipovitch G, Greaves MW, Fleischer AB, McGlone F, eds. Itch: Basic Mechanisms and Therapy. (pp. 305-315). New York: M. Dekker, 2004.

  7. Miller M, Bobrowski P, Shukla M et al: Chondroprotective effects of a proanthocyanidin rich Amazonian genonutrient reflects direct inhibition of matrix metalloproteinases and upregulation of IGF-1 production by human chondrocytes.  J Inflammation, 2007, 4:16. 

  8. Miller M, Reuter B, Wallace J et al: A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient. J Translational Medicine, 2008, 6: 3. 

  9. Sandoval M, Okuhama N, Clark M et al: Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells. J Ethnopharm, 2002. 80:121-129. 

Previous Ingredient Next Ingredient

 

Back to Ingredient

 

PhytoZon® is manufactured and distributed exclusively by American Dream Nutrition, LLC., all rights are reserved.