Progrado® 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.

Both extracts affect over-stimulated sensory (afferent) neurons – nerves that sense stimuli, such as pain – 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.

Progrado® / Zangrado® Research

(1) Treatment of gastric ulcers and diarrhea with the Amazonian herbal medicine sangre de grado. American Journal of Physiology – Gastrointestinal and Liver Physiology, 2000, 279: G192–G200. (Download PDF #14)

In a study designed to evaluate its gastrointestinal effects, Zangrado facilitated the healing of experimental gastric ulcers, reducing myeloperoxidase activity, ulcer size, and bacterial content. It also reduced the expression of pro-inflammatory genes tumor necrosis factor-alpha, inducible nitric oxide synthase (iNOS), interleukin (IL)-1beta, IL-6, and cyclooxygenase-2 which were upregulated by the ulcer induction. Additionally, it impaired ileum secretory response to capsaicin but not to electrical field stimulation or an NK-1 agonist. In summary, Zangrado is a potent, cost-effective treatment for gastrointestinal ulcers and distress via antimicrobial, anti-inflammatory, and sensory afferent-dependent actions.

(2) Clinical Trial: Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado. Journal of Investigative Dermatology, 2001, 117(3): 725-730. (Download PDF #15)

In mechanism of action study, Zangrado was tested as a messentary vasorelaxant, for edema, hyperalgesia and gastric hyperemia and in a clinical study for the relief of itching, pain, discomfort, edema, and redness in response to wasps, ants, mosquitoes, bees, cuts and abrasions. Zangrado was found effective in all applications, acting via the potent inhibition of sensory afferent nerve mechanisms which supports its use for disorders characterized by neurogenic inflammation.

(3) Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells. Journal of Ethnopharmacology, 2002, 80: 121-129. (Download PDF #16)

Zangrado was evaluated for its potential role in the treatment of cancer using human stomach and colon cancer cells. Both cell viability and proliferation decreased, while apoptosis increased, upon treatment, similar to that observed with the pharmaceutical Taxol. A significant alteration of microtubular architecture was equally observed in both stomach and colon cancer cells exposed to Zangrado. This induction of apoptosis and microtubule damage suggests that Zangrado should be evaluated further as a potential source of anti-cancer agents.

(4) Chondroprotective effects of a proanthocyanidin rich Amazonian genonutrient reflects direct inhibition of matrix metalloproteinases and upregulation of IGF-1 production by human chondrocytes. Journal of Inflammation, 2007, 4: 16. (Download PDF #17)

Acute oral safety and toxicity of Zangrado and Progrado were evaluated. Of up to doses of 2000 mg/kg (po), neither displayed evidence of toxicity. Additionally, Progrado was shown to be a potent antioxidant in the standardized tests ORAC, NORAC and HORAC. It also prevented IL-1? induced suppression of IGF-1 production from human cartilage explants as well as stimulating basal IGF-1 production. Comparable changes in IGF-1 gene expression occurred in cultured human chondrocytes. In summary, both extracts have an excellent safety profile, and due to its significant chondroprotective and antioxidant actions, Progrado may offer therapeutic benefits in joint health, wound healing and inflammation.

(5) A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient. Journal of Translational Medicine, 2008, 6: 3. (Download PDF #18)

Zangrado was evaluated for the management of emesis and itch. Results indicate that it 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. It therefore represents a promising new approach to the management of nausea, itch and irritable bowel syndrome.

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