The red resin or "blood" as well as the bark of Sangre de Grado has a long history of indigenous use in the rainforest and South America. The earliest written reference dates its use to the 1600's when Spanish naturalist and explorer, P. Bernabé Cobo, found that the curative powers of the sap was widely known throughout the indigenous tribes of Mexico, Peru and Ecuador. For centuries, the sap has been painted on wounds to help stop bleeding, to accelerate healing and to seal and protect the injury from infection. The sap dries quickly and forms a barrier like a second skin. It is used internally as well as externally by indigenous tribes and local people in Peru for wounds, leucorrhea, fractures and piles as well as for intestinal and stomach ulcers. Other indigenous uses include using it for intestinal fevers and pyorrhea in vaginal baths before childbirth, for hemorrhaging after childbirth, and for skin disorders.

Sangre de Grado resin and bark is used in traditional medicine in South America with its uses closely following the indigenous uses. It Peruvian herbal medicine it is widely used and recommended for external use as a wound healing agent and as an antiseptic vaginal douche, for skin disorders like eczema, and to relieve itchy bug bites. It is taken internally for hemorrhaging, mouth ulcers in the mouth, tonsillitis, throat infections, tuberculosis, peptic ulcers, intestinal disorders, rheumatism and to enhance fertility. In Brazilian traditional medicine the sap is used for wounds, hemorrhaging, mouth ulcers and a general tonic. Although thousands of pounds of bark and resin are imported into the United States currently, American consumers and practitioners know very little of Sangre de Grado and its effective uses. Rather, imports of Sangre de Grado are going to a U.S.-based pharmaceutical company, Shaman Pharmaceuticals, Inc. Shaman has developed two pharmaceutical drugs which contain antiviral constituents they isolated and extracted from the bark and resin of Sangre de Grado. Their drugs include Provir, an oral product for the treatment of respiratory viral infections and Virend, a topical antiviral product for the treatment of herpes.

Since much of the research on Sangre de Grado has been performed in the course of developing proprietary drugs, most of the research has not been published or made available to the public. The active constituents in Sangre de Grado include proanthocyanadins (antioxidants), tannins, a lignan named dimethylcedrusine, and an alkaloid called taspine. Other research on taspine in 1977 indicates that it has demonstrated the ability to inhibit RNA-directed DNA polymerase activity in the myeloblastosis virus, Rauscher leukemia virus and Simian sarcoma virus. The taspine alkaloid from Sangre de Grado was first documented with anti-inflammatory actions in 1979. In 1985, taspine was again documented with anti-inflammatory, antisarcomic, and antiviral actions. The cicatrizant or wound healing action of Sangre de grado resin was first attributed to the alkaloid taspine in 1989. Several later studies in 1991 and 1993 also concentrated on the wound healing and antitumor properties of taspine. The lignan, dimethylcedrusine, was isolated by scientists in 1993 and was shown to a play a central role in Sangre de Grado's effective wound healing action as well. This Belgium study revealed that the crude resin stimulated contraction of wounds, helped in the formation of a crust at the wound site, regenerated skin more rapidly and assisted in the formation of new collagen. While the lignan was found to stimulate collagen formation, the crude resin was found to be four times more effective at wound healing and collagen formation than the lignan or the isolated alkaloid, taspine. The Belgium scientists also determined that taspine was active against herpes, however according the Shaman Pharmaceuticals, neither taspine nor dimethylcedrusine is the source of their new drugs. In 1994, other phytochemicals were found, including phenolic compounds, proanthocyanadins and diterpenes, which showed potent anti-bacterial activity as well as wound healing properties.

To date, 4 U.S. patents have been filed on Sangre de grado resin by two different pharmaceutical companies. The first by Walter Lewis, et.al. in 1992 showed issolating the taspine alkaloid from the resin and dissolving it in a DMSO carrier for wound healing. Another patent was filed in 1995 by Walter Lewis and WoundFast Pharmaceuticals, Inc., further documenting the taspine preparation they developed from the resin and it's effective uses to heal wounds more rapidly. The second company was Shaman Pharmaceuticals who filed their first patent in 1993, describing their methods for extracting a proanthocyanidin polymer chemical isolated in the resin and bark of the tree and treating animals and humans infected with respiratory syncytial virus, influenza A, B and C, and Herpes Simplex virus citing numerous clinical experiments they performed. They filed a second patent in 1996, continuing to document the antiviral properties, uses, and clinical testing and results of their extract from Sangre de grado resin and bark against numerous viruses.

As the research reveals, the indigenous uses of Sangre de Grado have certainly been validified. It is a wonderful new sustainable rainforest resource which consumers should learn about and take advantage of as it becomes available in the market place. It is helpful for all types of cuts, scrapes, external wounds, rashes and skin problems, simply being applied directly to the affected area. It also quickly relieves the sting and itch of insect bites. Most recently, North American practitioners are reporting it to be helpful in cases of stomach ulcers, ulcerative colitis and Crohn's when taken internally. Internal dosages based on documented indigenous uses and South American herbal medicine practices are generally 10 to 20 drops of resin placed in water and taken once to two times daily.

Known as Sangre de Grado, Spanish for "Blood of the Dragon," because of its thick red sap, Croton lechleri grows throughout the Amazon. Its sap has been used for centuries by indigenous peoples of the Amazon as a herbal medicine to treat wounds, ease pain and relieve gastrointestinal distress. Wallace and his research team are conducting experimental research on Sangre de Grado as a potent inhibitor of inflammation and pain.

“Not only does Sangre de Grado prevent pain sensation, it also blocks the tissue response to a chemical released by nerves that promotes inflammation. There is currently no other substance that we know of that shares these same activities,” says Wallace. In laboratory tests, Wallace’s research team has demonstrated that Sangre de Grado blocks the activation of nerve fibers that relay pain signals to the brain, therefore functioning as a broad-acting pain killer.

In a clinical trial performed with pest control workers in Louisiana, a balm made from Sangre de Grado was found to provide relief from the bites and stings of a wide variety of insects within 90 seconds. The study further shows that Sangre de Grado offers pain relief and alleviated symptoms - itching and swelling - for up to six hours. Similar types of pain and inflammation can occur in the gastrointestinal tract - with gastritis, ulcer disease and infectious diarrhea. Wallace says, “We find that in animals with these conditions, the sap promotes gastrointestinal healing.”

Sangre de Grado has antibacterial actions, showing excellent promise as a first aid treatment for insect bites and stings, lacerations and even burns. Wallace, who performed these studies in collaboration with researchers at Albany Medical College in Albany, NY, says that isolation of the active ingredient in Sangre de Grado could lead to new therapies for a wide range of inflammatory diseases, including asthma, arthritis and ulcerative colitis.

This research is supported by the Medical Research Council and the Alberta Heritage Foundation for Medical Research.

The Green Pharmacy, James A. Duke, Rodale 1997
"Dragon's blood (Croton lechleri). Several compounds in it, among them dimethylcedrusine and taspine, have antiviral and wound-healing properties that may be especially useful against the viral sores caused by herpes. The natural mixture of all three coumpounds heals wounds four times faster than the individual compounds alone. I use dragon's blood when I get cuts or abrasions in tropical Peru. Unfortunately, this herb is not widely available in the United States, although I expect that it will be soon. It is applied externally."

10. "Croton lechieri Muell.-Arg. Euphorbiaceae. "Sangre de drago", "Sangre de grado", "Dragon's blood". The latex is used to heal wounds, and for vaginal baths before childbirth. It is also recommended for intestinal and stomach ulcers (RVM). It yields the hemostatic sap that accelerates wound healing (NIC). For leucorrhea, fractures, and piles (RAR)."

17."The sangre de grado tree was only a few minutes beyond. A tall slender tree, with smooth pale bark, it didn't look at all juicy, but when Dona Luisa slashed it wtih her machete, sap the color and consistency of blood flowed as from a wound. I was elated as I held a cup to catch the liquid. I'd wanted it for so long! This I knew was a most effective hemostatic agent; it was one of the plants the pharmaceutical company wanted especially, the one I'd used externally to stop the bleeding from a bad cut on my arm. The medicine I had seen given by mouth to stop internal bleeding in a woman hemorrhaging after childbirth. I knew this one could save lots of lives."
"Two of the plants had been scientifically identified for me by a Peruvian botanist who spent a day or two at the hotel. They were among the more important plant medicines, I thought. And the sangre de grado, which taken by mouth stops internal bleeding of a wound and applied externally disinfects and stops bleeding of a wound, was a Euphorbiacea, Croton salutaris; C.planostigma Klotzch."

Web Resources

Clinical References & Abstracts from Medline on Sangre de grado
from Medline on Taspine
U.S. Patents filed on Sangre de grado

Taspine is the cicatrizant principle in Sangre de Grado extracted from Croton lechleri.
Vaisberg AJ; Milla M; Planas MC; Cordova JL; de Agusti ER; Ferreyra R; Mustiga MC; Carlin L; Hammond GB
Planta Med, 55: 2, 1989 Apr, 140-3
Sangre de Grado extract used by Peruvian natives as a cicatrizant agent, was collected from trees of the species Croton lechleri growing in the Peruvian jungle. The Sangre de Grado was found to contain one alkaloid identified as taspine and which was shown to be the active cicatrizant principle by an in vivo test in mice. This alkaloid exhibited a dose-related cicatrizant effect and an ED50 of 0.375 mg/kg. Experiments with taspine hydrochloride in order to study its mechanism of action in cell culture systems showed that the alkaloid was non-toxic to human foreskin fibroblasts at concentrations below 150 ng/ml and that it had no effect on cell proliferation. On the other hand, taspine hydrochloride was found to increase the migration of human foreskin fibroblasts. This effect on the migration of fibroblasts is probably the mechanism by which Sangre de Grado and taspine hydrochloride accelerate the wound healing process. Using the two-stage mouse skin carcinogenesis system, we have been able to show that neither Sangre de Grado nor taspine hydrochloride had carcinogenic or tumour promoter activity after 17 months of treatment.

Isolation of a dihydrobenzofuran lignan from South American dragon's blood (Croton spp.) as an inhibitor of cell proliferation.
Pieters L; de Bruyne T; Claeys M; Vlietinck A; Calomme M; vanden Berghe D
University of Antwerp, Belgium.
J Nat Prod, 56: 6, 1993 Jun, 899-906
Dragon's blood is a red viscous latex extracted from the cortex of various Croton spp. (Euphorbiaceae), most commonly Croton lechleri, Croton draconoides (or Croton palanostigma), and Croton erythrochilus. It is used in South American popular medicine for several purposes, including wound healing. Bioassay-guided fractionation of dragon's blood, using an in vitro test system for the stimulation of human umbilical vein endothelial cells, has resulted in the isolation of a dihydrobenzofuran lignan, 3',4-O-dimethylcedrusin or 4-O-methyldihydrodehydrodiconiferyl alcohol [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-methoxybenzo furan-5- propan-1-ol] [1] as the biologically active principle. A related compound, 4-O-methylcedrusin [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-hydroxybenzo furan-5- propan-1-ol] [2], and the alkaloid taspine [3], also isolated from dragon's blood, were not active in the same assay. A cell proliferation assay, measuring the incorporation of tritiated thymidine in endothelial cells, showed that compound 1 did not stimulate cell proliferation, but rather inhibited thymidine incorporation, while protecting cells against degradation in a starvation medium.

Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon's blood.
Chen ZP; Cai Y; Phillipson JD
Department of Pharmacognosy, School of Pharmacy, University of London, U.K.
Planta Med, 60: 6, 1994 Dec, 541-5
Three in-vitro assays have been adopted to examine the cytotoxicity and anti-bacterial activity of the blood-red sap of Croton lechleri from Ecuador, and to examine its effect upon the proliferation of endothelial cells. The sap was found not to be cytotoxic. Several simple phenolic compounds and diterpenes showed a potent anti-bacterial activity. The sap has little effect upon the proliferation of endothelial cells, and no single active ingredient was identified. A mechanism for the wound-healing property of the sap has been proposed.

A cytotoxic substance from Sangre de Grado.
Itokawa H, Ichihara Y, Mochizuki M, Enomori T, Morita H, Shirota O, Inamatsu M, Takeya K
Tokyo College of Pharmacy, Japan.
Chem Pharm Bull (Tokyo) 1991 Apr;39(4):1041-1042
Taspine has been isolated as a cytotoxic substance from Sangre de Grado, sap of Croton palanostigma (Euphorbiaceae), by bioassay guided fractionation. The cytotoxicity (IC50) of taspine was found to be 0.39 microgram/ml against KB cells and 0.17 microgram/ml against V-79 cells.

A matter of some sensitivity.
Phillipson JD
Department of Pharmacognosy, School of Pharmacy, University of London, U.K.
Phytochemistry, 38: 6, 1995 Apr, 1319-43
he development of sensitive chromatographic and spectroscopic techniques for the isolation and structure determination of natural products has greatly facilitated phytochemical investigations. Chemical investigations of herbarium material have resulted in the isolation of indole, quinoline and isoquinoline alkaloids from a wide number of plants. Examples of novel natural products from higher plants are given and include alkaloids, terpenoids, phenolics and quinones. Some plants investigated have not yielded the types of constituents which would have been predicted from them. Plant tissue cultures provide alternative sources of biologically active compounds and examples investigated include Cinchona, Ailanthus, Brucea and Artemisia for antiprotozoal compounds and Datura for tropane alkaloids. Biological tests are useful for bioassay-guided fractionation of plant extracts and examples of the isolation of a series of natural products with antiprotozoal and cytotoxic activities are given. Chemical and biological investigations into the traditional medicine Dragon's blood (Croton lechleri) from S. America and a Chinese prescription for the treatment of atopic eczema are described. The use of radio-ligand binding assays for the detection of a wide range of biological activities is discussed. Sensitivity of chemical and biological techniques has greatly improved prospects for finding new drug entities from plants and for investigating traditional medicines. Basic phytochemical investigations should continue to be encouraged especially in view of the rapid loss of plant species.

Enhancement of wound healing by the alkaloid taspine defining mechanism of action.
Porras-Reyes BH, Lewis WH, Roman J, Simchowitz L, Mustoe TA
Division of Plastic Surgery, Washington University School of Medicine, Saint Louis, Missouri
Proc Soc Exp Biol Med 1993 May;203(1):18-25
Taspine (mol wt 369,000) is an alkaloid extracted from trees of Croton (family Euphorbiaceae) of the western Amazon region that has been used by natives and others as a vulnerary agent. Taspine was purified from tree sap to test its healing properties using different topical concentrations in the paired rat surgical incision model. Wound tensile strength and histology were evaluated. Samples treated with 250 micrograms, but not those treated with 50 micrograms or 10 micrograms, had significant higher values for MBS than paired controls (26%, P < 0.005, and 30%, P < 0.001, by Days 5 and 7, respectively). Taspine did not modify MBS at Day 12. Sample treated with 250 micrograms had significantly greater mononuclear cellular infiltration at Days 5 and 7 but not at Day 12. To better understand the effect of taspine as an enhancer of wound healing, we conducted in vitro studies in cell cultures. Taspine stimulated chemotaxis for fibroblasts. Taspine did not have an effect on specific assays for macrophage chemotaxis, neutrophil activation, fibroblast proliferation, or matrix assembly. Taken together, the data suggest that taspine promotes early phases of wound healing in a dose-dependent manner with no substantial modification thereafter. Its mechanism of action is probably related to its chemotactic properties on fibroblasts and is not mediated by changes in extracellular matrix.