Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado

J Invest Dermatol. 2001 Sep;117(3):725-30. doi: 10.1046/j.0022-202x.2001.01446.x.


This study was designed to determine if the Amazonian medicinal sangre de grado, confers benefit by suppressing the activation of sensory afferent nerves.

Methods: (i) vasorelaxation of rat mesenteric arteries in response to calcitonin gene-related peptide; (ii) rat paw edema in response to protease- activating peptide receptor 2-activating peptide; (iii) rat paw hyperalgesia in response to low-dose protease-activating peptide receptor 2-activating peptide or prostaglandin E2; (iv) gastric hyperemia in response luminal capsaicin; (v) a clinical trial of a sangre de grado balm in pest control workers. The parent botanical was fractionated for evaluation of potential active components. In preconstricted rat mesenteric arteries, highly diluted sangre de grado (1:10,000) caused a shift to the right of the calcitonin gene-related peptide dose-response curve (p < 0.01). Paw edema in response to protease-activating peptide receptor 2-activating peptide (500 microg) was reduced by as single topical administration sangre de grado balm (1% concentration, p < 0.01) for at least 6 h. Hyperalgesia induced by either low-dose protease-activating peptide receptor 2-activating peptide (50 microg) or prostaglandin E2 was prevented by sangre de grado balm. A fraction possessing analgesic and capsaicin antagonistic properties was isolated and high-performance liquid chromatography and gas chromatography-mass spectrometry analysis indicated that it was a proanthocyandin oligomer. In pest control workers, sangre de grado balm (Zangrado) was preferred over placebo, for the relief of itching, pain, discomfort, edema, and redness in response to wasps, fire ants, mosquitoes, bees, cuts, abrasions, and plant reactions. Subjects reported relief within minutes. We conclude that sangre de grado is a potent inhibitor of sensory afferent nerve mechanisms and supports its ethnomedical use for disorders characterized by neurogenic inflammation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / pharmacology
  • Capsaicin / pharmacology
  • Edema / drug therapy
  • Female
  • Humans
  • Hyperemia / drug therapy
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / physiopathology
  • Neurogenic Inflammation / drug therapy*
  • Neurogenic Inflammation / physiopathology
  • Phytotherapy*
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Rats
  • Rats, Inbred F344
  • Receptor, PAR-2
  • Receptors, Thrombin / agonists
  • Stomach / physiopathology
  • Vasodilation / drug effects


  • Plant Extracts
  • Receptor, PAR-2
  • Receptors, Thrombin
  • sangre de grado
  • Calcitonin Gene-Related Peptide
  • Capsaicin