Dragon's Blood

Scientific Name(s): Croton lechleri Muell.-Arg. Family: Euphorbiaceae (spurges)

Common Name(s): Dragon's blood , sangre de grado , sangre de drago , drago

Uses

Dragon's blood has been used for its antiviral, wound healing, and GI benefits.

Dosing

The standardized dragon's blood product SP-303 ( Provir ) has been studied for diarrhea at doses of 125 to 500 mg daily. 1

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

There have been no major toxicities reported with the use of dragon's blood.

Toxicology

No data available.

Botany

The genus croton contains about 750 species of trees and shrubs commonly found in tropical and subtropical regions of both hemispheres. This tree grows from 10 to 20 m in height. The trunk is covered with smooth, mottled bark, which when cut or “wounded,” oozes a red, sappy resin that makes it appear as if the tree is “bleeding.” 2

Red resin from the genus Daemonorops draco , used to color varnishes and lacquers, is the common dragon's blood of commerce, 3 and is an entirely different plant than C. lechleri . Since C. lechleri latex is sold in Peru and elsewhere, it is also “of commerce” though not as widespread as the Daemonorops resin.

History

Sangre de grado, Spanish for “blood of the dragon,” has a long history of use for both the bark and the resin. An early reference dating back to the 1600s notes that Spanish explorer P. Bernabe Cobo found the sap was being used by indigenous tribes throughout Peru and Ecuador. They used it internally and externally to stop bleeding, help heal wounds, and treat intestinal problems. Studies regarding this plant date back to the late 1970s. Preparations made from dragon's blood are found in several pharmaceutical products, some of them patented.

Chemistry

Alkaloid taspine has been isolated from C. lechleri . 4 Diterpenes and polyphenolic compounds including proanthocyanidins (90%), catechins, epicatechins, gallocatechins, and related structures have been found in the sap. 5 , 6 Clerodane diterpenoids including korberin A and B have been isolated as well. 7 A dihydrobenzofuran lignan; 3′,4-O-dimethylcedrusin, has been found in the latex. 8 Volatile constituents from C. lechleri sap, as determined by GC/MS analyses, include ethyl acetate, ethyl propionate, 2-methylbutanol, 2-methyl-bu acetate, Pr acetate, 3-methyl-bu acetate, eucalyptol, 1-bu acetate, and 3-methyl-2-pentanol. 9 Other phytochemicals reported from the plant include pinenes, camphene, eugenol, linalool, pectic acid, tannin, vanillin, and resin. 2 One report suggests the presence of pro-oxidant compounds. 10 Another report provides the synthesis of methyl dihydrohardwickiate from crolechinic acid isolated from C. lechleri 11 with the goal of generating useful derivatives.

Sinoacutine has been isolated from C. lechleri leaves. 12 A review on certain techniques for isolation of natural products is available, including chemical and biological investigations of dragon's blood in particular. 13

Uses and Pharmacology

C. lechleri resin and bark are used in traditional medicine in South America. Externally, it is employed as an antiseptic, as a wound-healing agent, and for skin disorders. Internally, it is used for hemorrhaging, mouth and throat ulcers/infections, and intestinal disorders. 2 This important “rainforest resource” has several uses that have been validated by several studies.

Antibacterial and antiviral effects
Animal data

Several phenolic compounds and diterpenes have demonstrated potent antibacterial activity. 7 , 14 Antiviral effects are seen from C. lechleri as well. A large proanthocyanidin oligomer isolated from the latex demonstrates broad activity against DNA and RNA viruses, including RSV, influenza A, parainfluenza virus, herpesvirus types 1 and 2, and hepatitis A and B viruses. 15 Constituent taspine inhibited RNA-directed DNA polymerase activity from certain virus types, including leukemia and sarcoma virus. 16

Clinical data

Research reveals no clinical data regarding the use of dragon's blood as an antibacterial or antiviral agent.

Wound-healing effects
Animal data

The taspine alkaloid from dragon's blood was first documented with anti-inflammatory actions in 1979. 4 Later studies confirmed these actions, leading to further studies in the area of wound healing. Taspine was found to be the healing principle, as in 1 study by in vivo testing in mice. Increased migration of human fibroblasts was suggested as the probable mechanism in this acceleration of the wound-healing process. 17 Another report evaluating taspine's wound-healing properties demonstrated positive results (with higher dosing, earlier seen than later), using such parameters as wound tensile strength and histology. Taspine also was found to stimulate chemotaxis for fibroblasts. Data from the report suggest that taspine promotes early phases of wound healing in a dose-dependent manner. 18 A patent was issued for taspine in DMSO (solvent), which healed wounds faster than DMSO alone or no treatment at all. 19 Another dragon's blood constituent, a dihydrobenzofuran lignan also involved in wound healing actions, was isolated in 1993. 8

Clinical data

Research reveals no clinical data regarding the use of dragon's blood for wound healing.

GI effects
Animal data

Research reveals no animal data regarding the use of dragon's blood for GI effects.

Clinical data

Dragon's blood also plays a role in GI health. Practitioners are reporting it beneficial for stomach ulcers, ulcerative colitis, and Crohn's disease when taken internally. Ten to 20 drops of the resin in water once to twice daily is the regimen based on South American herbal medicine practices. 2 A patent describing use of the proanthocyanidin polymer from croton species as an antidiarrheal was issued to Shaman Pharmaceuticals, Inc. USA. 20 The company's natural dietary supplements containing standardized extract from C. lechleri sap are called NSF 21 and NSF-1B. 22 The products claim “clinically demonstrated relief from diarrhea that won't cause constipation.” Normalization of diarrhea caused by excess fluid secretion into the intestinal tract is the suspected mechanism of action. 23 A double-blind, randomized, placebo-controlled trial of the principal ingredient (SP-303) in patients with HIV-associated diarrhea demonstrated beneficial effects. 24

Other uses

One report describes protective effects of C. lechleri latex on spontaneous lipid peroxidation in rat livers. 25 Taspine, isolated from C. palanostigma sap, has been isolated as a cytotoxic substance. 26

Dosage

The standardized dragon's blood product SP-303 ( Provir ) has been studied for diarrhea at doses of 125 to 500 mg daily. 1

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

No major toxicity has been reported from dragon's blood. The natural product (NSF) web page mentions its safety and efficacy in clinical testing involving more than 1200 patients. No interactions were observed. 21 One report found taspine to be nontoxic to human foreskin fibroblasts. 17

There is no safety data regarding pregnancy. The American Herbal Products Association lists dragon's blood as Class I, meaning it can be consumed safely when used appropriately. 27

Toxicology

Research reveals little or no information regarding toxicity with the use of this product.

Bibliography

1. DiCesare D, DuPont HL, Mathewson JJ, et al. A double blind, randomized, placebo-controlled study of SP-303 ( Provir ) in the symptomatic treatment of acute diarrhea among travelers to Jamaica and Mexico. Am J Gastroenterol . 2002 Oct;97(10):2585-2588.
2. http://www.rain-tree.com/sangre.htm
3. http://www.mcs.drexel.edu/~gslombey/Personal/Sangre.html
4. Perdue G, et al. South American plants II: Taspine isolation and anti-inflammatory activity. J Pharm Sci . 1979;68(1):124-126.
5. Cai Y, et al. Biological and chemical investigation of dragon's blood from Croton species of South America. Part 1. Polyphenolic compounds from Croton lechleri . Phytochemistry . 1991;30(6):2033-2040.
6. Cai Y, et al. Biological and chemical investigation of dragon's blood from Croton species of South America. Part 2. Diterpenes from Croton lechleri . Phytochemistry . 1993;32(3):755-760.
7. Cai Y, et al. Biological and chemical investigation of dragon's blood from Croton species of South America. Part 3. Clerodane diterpenoids from Croton lechleri . Phytochemistry . 1993;34(1):265-268.
8. Pieters L, 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;56(6):899-906.
9. Bellesia F, et al. Headspace analysis of Croton lechleri L. sap. J Essent Oil Res . 1996;8(4):435-437.
10. Desmarchelier C, et al. Effects of sangre de drago from Croton lechleri Muell.-Arg. on the production of active oxygen radicals. J Ethnopharmacol . 1997;58(2):103-108.
11. Costa M, et al. Synthesis of methyl dihydrohardwickiate and its C-4 epimer. Structural amendment of natural crolechinic acid. Phytochemistry . 2000;53(8):851-854.
12. Carlin L, et al. Isolation of sinoacutine from the leaves of Croton lechleri . Planta Med . 1996;62(1):90-91.
13. Phillipson J. A matter of some sensitivity. Phytochemistry . 1995;38(6):1319-1343.
14. Chen Z, et al. Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon's blood. Planta Med . 1994;60(6):541-545.
15. Ubillas R, et al. SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (sangre de drago). Phytomedicine . 1994;1(2):77-106.
16. Sethi M. Inhibition of RNA-directed DNA polymerase activity of RNA tumor viruses by taspine. Can J Pharm Sci . 1977;12(1):7-9.
17. Vaisberg A, et al. Taspine is the cicatrizant principle in sangre de grado extracted from Croton lechleri . Planta Med . 1989;55(2):140-43.
18. Porras-Reyes B, et al. Enhancement of wound healing by the alkaloid taspine defining mechanism of action. Proc Soc Exp Biol Med . 1993;203(1):18-25.
19. Lewis W, et al. Wound-healing compositions . U.S. Patent 5156847, Oct. 20, 1992.
20. Rozhon E, et al. Enteric formulations of proanthocyanadin polymer antidiarrheal compositions. #WO 9816111, Apr. 23, 1998.
21. http://www.diarrheasolutions.com .
22. http://www.nsfib.com .
23. Gabriel, et al. A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion. Am J Physiology . 1999;279(39):G58-G63.
24. Holodniy, et al. A double blind, randomized, placebo-controlled, phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS. Amer J Gastroenterology . 1999;94(11):3267-3273.
25. Desmarchelier C, et al. Protective effects of “sangre de drago” from Croton lechleri Muell.-Arg. on spontaneous lipid peroxidation. R Soc Chem . 1999;240:272-274.
26. Itokawa H, et al. A cytotoxic substance from sangre de grado. Chem Pharm Bull (Tokyo) . 1991;39(4):1041-1042.
27. American Herbal Products Association. American Herbal Products Association Botanical Safety Handbook . Boca Raton, FL: CRC Press, 1997.

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