sangre de dragón

Dragon's Blood: A Comprehensive Reference

1. Identity, Nomenclature, and Botanical Sources

Dragon's blood is a bright red resin obtained from different species of four distinct plant genera: Croton, Dracaena, Daemonorops, and Pterocarpus. The red resin has been in continuous use since ancient times as varnish, medicine, incense, pigment, and dye. Although the name is applied broadly, the botanical sources are chemically distinct and should not be treated as interchangeable.

1.1 Croton lechleri Müll. Arg. (South American Dragon's Blood)

The genus Croton comprises approximately 750 species of trees and shrubs commonly found in tropical and subtropical regions. C. lechleri is a medium-sized tree that grows approximately 15 m in height, and the trunk is covered with smooth, mottled bark. When the bark is cut or damaged, it oozes a red, sap-like resin, which makes the tree appear to be bleeding. Croton lechleri (Euphorbiaceae) is found in Peru, Ecuador, Colombia, and northern Brazil. Croton urucurana is usually sighted in the southeast, mid-west, and southern regions of Brazil, as well as in Argentina and Uruguay. Both species are relatives and their respective sap has a similar pharmacological activity.

Common names include: Blood of the Dragon, Crofelemer, Drago, Dragon's Blood, Sangre de Drago, Sangre de Grado, and SP-303. Dragon's blood is also referred to as "Sangre de drago" in Peru and "Sangre de grado" in Ecuador. Other species within the dragon's blood complex of the Croton genus include C. draco, C. palanostigma, C. sordidus, C. urucurana, and C. xalapensis.

1.2 Dracaena Species

Dragon's blood — the red resin produced by tree species in the genus Dracaena (Asparagaceae) — is a precious traditional Chinese medicine and a folk medicine used by many nationalities in the world. It has several therapeutic functions of activating blood circulation and dissipating blood stasis, relieving inflammation and pain, astringency and hemostasis. Six Dracaena species are well documented: D. cochinchinensis, D. cambodiana, D. cinnabari, D. draco, D. loureiri, and D. schizantha. All these plants are rich in flavones, flavanones, homoisoflavanones, dihydrochalcones, homoisoflavanes, stilbenes, phenolic oligomers, and other phenolic compounds; thus far, 185 phenolic compounds have been identified.

Dracaena cinnabari is an endemic plant located on Socotra Island, Yemen. Deep red resin attained from this species is commonly known as dragon's blood. Voyagers to the Canary Islands in the 15th century obtained dragon's blood as dried garnet-red drops from Dracaena draco, a tree native to the Canary Islands and Morocco. The resin is exuded from its wounded trunk or branches. Dragon's blood is also obtained by the same method from the closely related Dracaena cinnabari, which is endemic to the island of Socotra. This resin was traded to ancient Europe via the Incense Road.

1.3 Daemonorops / Calamus Species (Southeast Asian Dragon's Blood)

Daemonorops draco, a rattan palm native to Malaysia and Indonesia, produces much of the dragon's blood of commerce. Dragon's blood resin is also produced from the rattan palms of the genus Calamus (formerly Daemonorops) of the Indonesian islands and known there as jernang or djernang. It is gathered by breaking off the layer of red resin encasing the unripe fruit of the rattan. Dragon's blood derived from species of Dracaena and Daemonorops is a phenolic resin, with well-recognized chemical content.

1.4 Common Forms and Preparations

Dragon's blood is a red resin obtained from the sap of several species of plants that is used as a varnish, paint pigment, and dye, but also as a traditional medicine, used topically as an astringent and orally as treatment for diarrhea and digestive diseases. In contemporary commerce, dragon's blood is sold in a wide variety of formulated forms: it is available as creams, gels, serums, masks, sprays, mouthwash, toothpaste, resin, powder, capsules, tablets, liquid, or tinctures. Crofelemer, the active ingredient in the pharmaceutical product Mytesi, is a botanical drug substance extracted and purified from the red bark sap of the Croton lechleri tree found in the Amazon rainforest. The sap of Croton lechleri is collected by making incisions in the bark, and it can be used fresh, dried to a powder, or processed into standardized extracts.

2. Traditional and Historical Use

2.1 Ancient Mediterranean Cultures

Dragon's blood has a legacy as a pigment, dye, and potential remedy for respiratory and gastrointestinal concerns since ancient Greek, Roman, and Arab times. Greek physician Dioscorides was among the first to describe its therapeutic uses. In the Arab world, it was called the "blood of two brothers," while first-century Roman texts referenced it as the blood of a dragon crushed by an elephant. Historical records of the Romans and Greeks also note Dracaena cinnabari, found on an island in the Indian Ocean. The resin of Dracaena species — the "authentic" dragon's blood — and the extremely poisonous mineral cinnabar (mercury sulfide) were often confused by the ancient Romans.

Some medieval encyclopedias claimed its source as the literal blood of elephants and dragons who had perished in mortal combat. Dragon's blood, despite being used for paint, was also used for various medical applications during the period between 1880 and 1914 as a type of "cure-all, stimulant, muscle-relaxant and abortifacient."

2.2 Traditional Use in Yemen and the Arab World

Dragon's blood (Dracaena) is used for treating dysentery, diarrhoea, hemorrhage and external ulcers in Yemeni folk medicine. Dracaena resin has strong astringent properties and is used as a muscle relaxant. Seventeenth-century botanical authorities documented that dragon's blood (Dracaena) was used for overflow of menses, in fluxes, dysenteries, spitting of blood and fastening of loose teeth. It was also used to treat gonorrhea, stoppage of urine, watery eyes, and minor burns.

2.3 Traditional Use in East and Southeast Asia

In China, the red resin of Dracaena cochinchinensis was used by local people for treatment of wounds, leucorrhea, fractures, diarrhoea and piles as well as for intestinal and stomach ulcers. Daemonorops resin is also used in traditional Chinese medicine to stimulate circulation, promote tissue regeneration by aiding the healing of fractures, sprains and ulcers and to control bleeding and pain. In traditional Chinese medicine, it is known as xue jie, used in various traditional preparations. Early Chinese herbal manuals from the Ming dynasty (circa 16th century) mention its use as a hemostatic agent — helping to stop bleeding. In the rainforests of Kalimantan, local Dayak tribes long prized the resin for sealing canoes and treating skin lesions.

2.4 South American Indigenous and Folk Traditions

The crude plant latex of C. lechleri is traditionally used in South American medicine for the treatment of diarrhea, wounds, inflammations, tumors, insect bites, and other conditions. The Spanish naturalist Bernabé Cobo recorded in the 1600s that indigenous tribes across Mexico, Peru, and Ecuador used Croton sap widely, primarily for wound care. Sap of Croton lechleri was also used to speed up internal healing after an abortion and in vaginal baths taken before childbirth. Croton's sap has been reviewed by many researchers for its therapeutic uses. In South America, the sap is still applied topically to cuts, insect bites, and herpes sores, and taken orally for gastrointestinal issues.

2.5 Non-Medicinal Historical Uses

The resin from Dracaena was used to make varnishes, tinctures, plasters, toothpaste, stains for horns to resemble tortoiseshell, wool dye, to decorate pottery, and as a cosmetic lipstick to the 18th century. Two versions of Dragon's Blood (Dracaena draco and Dracaena cinnabari) were used as a varnish for Stradivarius violins. There was also an 18th-century recipe for toothpaste that contained dragon's blood.

3. Phytochemistry: Key Constituents and Active Compounds

3.1 Croton lechleri Constituents

Studies identify proanthocyanidins as the predominant phytochemical group in terms of relative quantity. Additionally, other significant phytochemical groups include alkaloids, diterpenoids, phytosteroids, saponins, phenolics, and polyphenolics.

The most pharmacologically studied constituents include:

• SP-303 / Crofelemer: Crofelemer is a complex mixture of procyanidins and prodelphinidins with up to 30 (epi)catechin or (epi)gallocatechin units per molecule, resulting in a molecular mass of up to 9 kDa.
• Taspine: A number of chemicals were isolated in the late 1980s and 1990s and tested in cellular and animal models, for example identifying taspine as a cicatrizant (wound healing promoter). Taspine promotes wound healing via increased migration of fibroblasts to the wound site by acting as a chemotactic factor for fibroblasts.
• Additional phenolics: Active components in C. lechleri include proanthocyanidins, catechins, phenols, flavonoids, diterpenes, taspine, and sterols.

It is notable that the larger proanthocyanidins as a class have high antiviral activity, whereas most of the monomers are inactive.

3.2 Dracaena Species Constituents

Flavonoids and their oligomers are the primary chemical clusters distributed in Dracaena plants. Pharmacological activities including analgesic, anti-inflammatory, antibacterial, hypolipidemic, hypoglycemic, and cytotoxic effects; bi-directional regulation effects on hemorheology; and cardiovascular and cerebrovascular effects have been disclosed by modern pharmacological evaluations.

Several phytochemicals have been isolated from D. cinnabari, including the biflavonoid cinnabarone, triflavonoids, metacyclophanes, chalcones, chalcanes, dihydrochalcones, sterols, and terpenoids. Among dihydrochalcones, loureirin A and B are considered as indicators for quality control of dragon blood from D. cinnabari.

In addition to flavonoids and stilbenoids, chemical and pharmacological studies have indicated that other phenolic compounds, saponins, and terpenes are the main effective compounds occurring in dragon's blood. Soqotri resin is a mixture of several phenolic derivatives with high content of flavonoid derivatives that are known as antioxidant compounds. Homoisoflavonoids and two isolated compounds from the Soqotri resin have been reported for their antioxidant activities: dracophane and a homoisoflavonoid, 7,8-methylenedioxy-3(4-hydroxybenzyl) chromane.

3.3 Mechanisms of Action

Antisecretory / Antidiarrheal Mechanism (Croton lechleri): Crofelemer is a first-in-class intraluminally active, use-dependent chloride (Cl⁻) ion channel modulator that produces an antidiarrheal effect by reducing Cl⁻ secretion and the accompanying high-volume fluid secretion into the GI lumen. SP-303, a mixture of proanthocyanidin oligomers, inhibited cAMP-mediated chloride secretion in two intestinal epithelial cell lines. The dual inhibitory action of crofelemer on two structurally unrelated prosecretory intestinal Cl⁻ channels may account for the intestinal antisecretory activity.

Wound Healing: Taspine promotes wound healing via increased migration of fibroblasts to the wound site by acting as a chemotactic factor for fibroblasts. When administered intraperitoneally, the resin demonstrated significant anti-inflammatory effects. However, taspine alone cannot be considered the primary compound responsible for these activities, suggesting that other constituents, likely proanthocyanidins, also play a significant role.

Antiviral Mechanism: The antiviral mechanism of SP-303 seems to derive from its direct binding to components of the viral envelope, resulting in inhibition of viral attachment and penetration of the plasma membrane.

Smooth Muscle Relaxation (Dracaena cinnabari): The aqueous extract of D. cinnabari resin has been shown to cause a concentration-dependent decrease of amplitude in phasic contractions. In albino male rats, it relaxes the tone of longitudinal segments of the ileum, uterus, and urinary bladder rings. This observation is consistent with the reported effects of other Dracaena species and dragon's blood-producing plants. The relaxant effect of the D. cinnabari resin aqueous extract may be attributed to the presence of hydrophilic flavonoids in the resin since different flavonoids have been shown to exert spasmolytic effects on smooth muscles.

4. Scientific Evidence by Area of Use

4.1 Antidiarrheal Activity — Strongest Human Evidence

The antidiarrheal application of C. lechleri latex has the most robust human clinical evidence of any application, culminating in regulatory approval.

Crofelemer, a single constituent of the C. lechleri tree, is approved by the US Food and Drug Administration (FDA) (brand name Mytesi) for symptomatic relief of noninfectious diarrhea in patients with HIV/AIDS who are receiving antiretroviral therapy. A Phase III clinical trial for diarrhea in HIV patients was completed in 2012, and the drug was approved by the FDA on 31 December 2012.

The pivotal clinical evidence includes: a double-blind, randomized, placebo-controlled Phase II study assessed the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS. Among 51 adults with AIDS and non-infectious diarrhea treated with SP-303 (crofelemer) or placebo every 6 hours for 4 days, reduction in stool weight was greater with crofelemer (−451 vs −150 g daily by day 4), and there were no serious adverse events or changes in laboratory values.

Crofelemer demonstrated reduction of duration of diarrhea and frequency of watery stools in patients with traveler's diarrhea and patients with HIV/AIDS. Crofelemer has also shown benefit in adult patients with acute infectious diarrhea from E. coli and salmonella, and in patients with moderate to severe watery diarrhea from Vibrio cholerae. Crofelemer has also been shown to improve abdominal pain and discomfort in patients with diarrhea-predominant irritable bowel syndrome.

In large clinical trials, crofelemer was found to decrease watery bowel movements and improve stool consistency in patients with HIV infection receiving antiretroviral therapy who had persistent diarrhea that could not be attributed to an infectious cause. Crofelemer was approved for use in the United States in 2013.

Evidence strength: Strong for the specific indication of noninfectious diarrhea in HIV/ART patients (supported by Phase II and Phase III RCTs, regulatory approval). Evidence for other diarrheal conditions (traveler's diarrhea, IBS-D) is supportive but based on smaller or less definitive trials.

4.2 Wound Healing

The array of phytochemical action in preclinical studies includes anti-inflammatory, antioxidant, antimicrobial, antifungal, and antineoplastic properties. Clinical studies reflect wound healing and antiviral properties.

One published randomized controlled clinical trial directly addressed wound healing: this clinical trial study was designated to evaluate the wound healing effect of dragon's blood on human wounds. Sixty patients, between the ages of 14–65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of the trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in dragon's-blood resin, are probably the main reasons for the wound healing property of this plant.

Being natural, accessible, safe, and affordable makes dragon's blood cream a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of dragon's blood.

Evidence strength: Preliminary. The single published RCT used a small population (n=60), employed a specific wound model (skin tag removal), and its findings require replication in larger, more diverse populations before firm conclusions can be drawn.

4.3 Antiviral Activity

SP-303, a large proanthocyanidin oligomer isolated from the latex of Croton lechleri, has demonstrated broad activity against a variety of DNA and RNA viruses. In cell culture, SP-303 exhibits potent activity against isolates and laboratory strains of respiratory syncytial virus (RSV), influenza A virus (FLU-A), and parainfluenza virus (PIV). Parallel assays of SP-303 and ribavirin showed comparable activity against these viruses. SP-303 also exhibits significant inhibitory activity against herpesvirus (HSV) types 1 and 2, including herpesviruses resistant to acyclovir and foscarnet. Inhibition was also observed against hepatitis A and B viruses.

However, the translation to human clinical benefit has been limited: the purified oligomeric proanthocyanidin fraction was first described in 1994 under the name SP-303 as an antiviral drug, but a study testing it for the treatment of herpes simplex did not show any benefit. A small clinical trial of topical SP-303 (Virend) for genital and anal herpes simplex lesions in AIDS patients was conducted, but the antiviral application was not ultimately developed further.

Evidence strength: Preclinical only for most antiviral claims. In vitro and animal model data are extensive, but human clinical evidence for antiviral applications is lacking or negative (herpes simplex).

4.4 Anti-inflammatory Activity

The anti-inflammatory capacities of C. lechleri are linked to several ethnomedicinal uses and pharmacological observations, as the inflammatory mechanism is involved in processes such as healing, ulcers, and intestinal disorders. The anti-inflammatory effect of the alkaloid taspine has been reported. Preclinical studies in animal models have supported anti-inflammatory activity, but dedicated anti-inflammatory human clinical trials are absent from the published literature.

Evidence strength: Preclinical. Mechanistic and animal studies are supportive; no dedicated human RCTs for inflammatory conditions have been published.

4.5 Antimicrobial Activity

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 strong antifungal and antioxidant activities of the whole raw resin (as solution in methanol) confirm the traditional preparation using the whole crude resin as powder in Socotra.

Evidence strength: In vitro / preclinical only. No human clinical trials specifically testing antimicrobial efficacy have been identified.

4.6 Antitumor / Cytotoxic Activity

In addition to their wound-healing and antitumor activities, C. lechleri resin and isolated proanthocyanidins have been shown to be effective in treating various diarrheal conditions, including those associated with HIV. Their anti-inflammatory properties contribute to improving this condition. In one study, the sap irreversibly altered the microtubule structure of cancer cells, preventing adhesion and inducing apoptosis. It also inhibited mutagenicity of 2-aminoanthracene, although the mechanism is unknown. Laboratory studies indicate that it can kill cancer cells, but no studies have been done in humans.

Evidence strength: In vitro and animal models only. Human evidence is absent.

4.7 Cardiovascular and Metabolic Effects (Dracaena Species)

Dragon's blood from Dracaena species is a valuable source of bioactive compounds, mainly flavonoids and their oligomers. Its potential therapeutic effects on different diseases are attractive, such as the notable effect on cardiovascular diseases. D. cinnabari resin has demonstrated antidiabetic and hypolipidemic effects in animal models.

Evidence strength: Preclinical / animal models. Human clinical data are absent.

4.8 Radiation Attenuation

Dragon's blood may have radioprotective effects in radiation-induced rat brain injury. This area of investigation is confined to animal studies.

Evidence strength: Animal models only.

5. Body Systems and Health Areas of Association

Laboratory and clinical evidence supports activity as an analgesic, hemostatic, antidiarrheal, antirheumatic, antitumor, antiviral, wound healing, cardio-protective, neuroprotective, anti-inflammatory, and antioxidant agent. More specifically, the body systems and health areas with documented associations are:

• Gastrointestinal system: Antidiarrheal (strongest clinical evidence); antiulcer activity; intestinal inflammation. C. lechleri resin and isolated proanthocyanidins have been shown to be effective in treating various diarrheal conditions, including those associated with HIV.
• Integumentary system (skin and wound healing): Preclinical properties include anti-inflammatory, antioxidant, antimicrobial, antifungal, and antineoplastic effects. Clinical studies reflect wound healing and antiviral properties.
• Immune and hematological system: Activating blood circulation, dissipating blood stasis, astringency, and hemostasis.
• Cardiovascular and metabolic system: Analgesic, anti-inflammatory, antibacterial, hypolipidemic, hypoglycemic, and cytotoxic effects; bidirectional regulation effects on hemorheology; and cardiovascular and cerebrovascular effects have been identified in preclinical evaluations of Dracaena species.
• Oral health: Historically used in toothpaste preparations; astringent properties relevant to gum and oral tissue care.
• Oncology (preclinical only): Antiproliferative and cytotoxic properties have been observed in laboratory models.

6. Dosage Forms and Reported Dosages

A variety of traditional uses are associated with dragon's blood resin or sap; however, evidence from clinical trials is insufficient to support dosing recommendations for C. lechleri in its crude or supplement form. Clinical data are lacking to provide dosing recommendations.

For the FDA-approved pharmaceutical form:

• Delayed-release tablets of 125 mg of crofelemer constitute the approved pharmaceutical product (Mytesi).
• One Mytesi 125-mg delayed-release tablet is taken twice daily.
• Crofelemer, at oral doses of up to 738 mg/kg/day (177 times the recommended human daily dose of 125 mg twice daily), had no effects on fertility or reproductive performance of male and female rats in preclinical safety studies.

For the Phase II HIV diarrhea trial: 51 adults with AIDS and non-infectious diarrhea were treated with SP-303 (crofelemer) or placebo every 6 hours for 4 days. The specific dose per administration used in that Phase II study is not separately stated in the available sources beyond that schedule.

7. Safety Considerations and Interactions

7.1 General Safety Profile

While its safety has not been evaluated in depth in large prospective studies in humans, dragon's blood is generally regarded as safe, and in several small clinical trials it has not been implicated in any severe adverse events. Therapy with dragon's blood has not been linked to elevations in serum enzymes or to instances of clinically apparent liver injury.

No major toxic effects from consumption of C. lechleri extract have been reported. Systemic absorption of crofelemer is minimal, and studies report low levels of GI-related adverse effects (e.g., abdominal pain, flatulence, dyspepsia).

Side effects of oral therapy with C. lechleri preparations have been mild nausea, bitter taste, and occasional diarrhea.

7.2 Taspine Cytotoxicity

Weak to no mutagenicity has been reported for the sap or essential oil of C. lechleri; however, the chemical constituent taspine is considered cytotoxic. This is relevant primarily to isolated taspine, not necessarily to the whole plant extract at traditional doses.

7.3 Oral Toxicity Data

A study on oral toxicity of the D. cinnabari resin methanol extract was performed on female Sprague Dawley rats. Acute and sub-acute oral toxicity tests found that the extract could be tolerated up to 2,000 mg/kg body weight.

7.4 Safety in Special Populations

Information regarding safety and efficacy in pregnancy and lactation is lacking. C. lechleri sap has been traditionally used as a vaginal bath before childbirth and for healing after an abortion; however, clinical data are insufficient to support these uses. The safety and effectiveness of Mytesi (crofelemer) have not been established in pediatric patients.

7.5 Drug Interactions

Case reports for interactions with C. lechleri extracts are lacking. Animal studies suggest crofelemer may worsen dacomitinib-induced diarrhea, although clinical relevance is not known. For the broader extract form used as a dietary supplement, formal drug interaction studies in humans have not been published in the peer-reviewed literature available through the sources reviewed.

7.6 Identification and Adulteration Concerns

A great degree of confusion existed for the ancients in regard to the source and identity of dragon's blood. This concern persists in modern commerce, as products from different botanical genera have distinct chemical profiles and safety/efficacy implications. Some of the pharmacological investigations reported only elementary methodologies and unreliable findings, and even worse, some important aspects were questionable or missing in these articles. This underscores the importance of sourcing dragon's blood products that clearly identify the botanical genus and species.

8. Research Gaps and Current Evidence Appraisal

The overall scientific evidence base for dragon's blood varies substantially by botanical source and intended application. Despite its extensive traditional use, a comprehensive review of the scientific studies conducted over the past two decades is lacking, which hinders a thorough understanding of the chemical and pharmacological characteristics of the species.

The clearest and most clinically validated application is the use of the purified proanthocyanidin fraction (crofelemer/SP-303) from Croton lechleri for noninfectious HIV-associated diarrhea, which has been evaluated in Phase II and Phase III randomized controlled trials and received FDA approval. Although its popularity is rising in Western medicine, C. lechleri offers limited use in dermatology and further investigation is necessary to gain further insight into its potential clinical implication. For Dracaena species, more than 120 papers dealing with dragon trees have appeared in recent years, indicating significant interest in their research, cultural uses and conservation. The most intensively investigated species are Dracaena cochinchinensis, D. cinnabari, D. draco, and D. cambodiana. Almost half of the papers deal with the chemical composition of resin and its bioactivity. Only a few studies are devoted to taxonomy and ethnobotany. Most findings in both the Dracaena and Croton literature outside of the antidiarrheal/crofelemer context remain at the in vitro or animal model stage and require human clinical confirmation.

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