Dragon's Blood — Benefits Deep Dive

Deep-Dive Articles

Table of Contents

1. Deep-Dive Articles
2. The Evidence in One Page
3. Evidence Ledger at a Glance
4. The Sap and the Drug Are Not the Same Thing
5. Open Questions
6. Key Research: Crofelemer, the Drug
7. Key Research: Wounds, Skin and Inflammation
8. Key Research: Which Plant Is Which
9. Key Research: Taspine, Toxicity and Safety
10. External Resources
11. Connections

The Evidence in One Page

What is solid

• A drug came out of this latex. Crofelemer, an oligomeric proanthocyanidin purified from Croton lechleri stem-bark latex, was approved by the US FDA in December 2012 for symptomatic relief of non-infectious diarrhoea in adults with HIV/AIDS on antiretroviral therapy.
• Its mechanism is well described. In cell experiments it inhibits two different chloride channels in the gut lining, CFTR and the calcium-activated channel TMEM16A. Chloride flowing into the gut drags water with it, so blocking that flow reduces watery stools.
• It stays in the gut. Several reviews describe it as minimally absorbed, acting locally.
• The chemistry of the latex is mapped. Proanthocyanidins dominate, and taspine is the only alkaloid found in the latex, at an average of 9% of dry weight across 22 sites in Peru and Ecuador.

What is weaker than it sounds

• The drug's benefit is modest. In the ADVENT trial, 17.6% of people on crofelemer 125 mg twice daily met the response definition over four weeks, against 8.0% on placebo.
• It did not work everywhere it was tried. A 12-week trial in 242 people with diarrhoea-predominant IBS did not improve stool consistency, frequency, urgency or adequate relief. A 51-patient chemotherapy-diarrhoea trial missed its primary endpoint.
• The skin evidence is mostly laboratory. Reviews mention positive clinical reports for wounds and insect-bite symptoms, but describe no large, independent, placebo-controlled trial of the crude sap.
• Human "dragon's blood" wound data are about another plant. The 14-trial pressure-ulcer meta-analysis concerns the Chinese resin Resina Draconis.

What raises concern

• The latex was mutagenic in the Ames bacterial test (with metabolic activation) and in yeast.
• The sap of a related species, Croton palanostigma, with taspine as its main identified compound, damaged DNA in mice at every dose tested.
• Taspine slowed the growth of human melanoma and colon cancer cells in culture at 0.1 µg/mL.
• There are no published human safety studies of the crude sap taken by mouth, and no pregnancy or drug-interaction data.

Evidence Ledger at a Glance

Ranked from strongest to weakest. Negative results and missing evidence are listed separately because they mean different things.

1. Established, human, drug: crofelemer reduces non-infectious diarrhoea in people with HIV on antiretroviral therapy (phase 3 RCT, FDA approval 2012). Modest effect size.
2. Established, human, drug safety: crofelemer was generally well tolerated, minimally absorbed, with no appreciable effect on HIV viral load or CD4 counts; LiverTox reports occasional enzyme elevations and no clinically apparent liver injury.
3. Established, laboratory: crofelemer blocks CFTR (maximum about 60%) and TMEM16A (maximum over 90%) chloride channels.
4. Established, chemical: proanthocyanidin-dominated latex with taspine as its sole latex alkaloid; three leaf chemotypes; regional variation.
5. Negative, human, drug: no improvement in bowel function endpoints in diarrhoea-predominant IBS; primary endpoint missed in chemotherapy-induced diarrhoea, with a reduction in grade 2 or worse episodes in cycle 2.
6. Reproducible, laboratory and animal: anti-inflammatory and immune-modulating effects of the latex (complement inhibition, slowed T-cell proliferation, reduced rat paw swelling by injection).
7. Laboratory only: toxicity to cancer cell lines by the sap, taspine, leaf and twig extracts; antioxidant and anti-glycation effects in the test tube and in cultured vessel cells.
8. Traditional, thinly tested in humans: wounds and insect bites. Positive clinical reports are mentioned in reviews; no large independent placebo-controlled trial is described.
9. Safety signal, laboratory and animal: mutagenic sap in bacterial and yeast tests; genotoxic related Croton sap in mice; cytotoxic taspine.
10. Absent: human pharmacokinetics, dose-finding, interaction and pregnancy data for the crude sap; long-term safety data even for the drug, according to a 2013 review.

The Sap and the Drug Are Not the Same Thing

This is the most important distinction for anyone reading about dragon's blood. It is easy to assume that because an FDA-approved drug comes from this tree, the sap shares its proof. The research does not support that inference, for four reasons:

1. Different composition. Crofelemer is a purified proanthocyanidin oligomer. The crude latex also contains taspine at around 9% of dry weight, along with diterpenoids, sterols, saponins and other compounds.
2. Different safety evidence. The drug's safety record comes from controlled trials of a defined substance. The latex itself has tested mutagenic in laboratory assays, and no human safety study of the crude latex has been published.
3. Different consistency. The latex varies by region and chemotype. Even the drug varies between lots, which is why regulatory scientists use it as a model of a complex-mixture drug.
4. Different indication. The drug was approved for one specific situation: non-infectious diarrhoea in adults with HIV on antiretroviral therapy. It was not approved for wounds, insect bites, ulcers, viral infections, IBS or cancer.

Open Questions

• Does the crude latex, applied to an ordinary cut or insect bite, change healing time or symptoms compared with a placebo or a simple dressing in a properly blinded trial?
• How much taspine, if any, reaches the bloodstream after sap is swallowed or applied to broken skin?
• Do the mutagenicity findings in bacteria and yeast translate into any risk in people at traditional doses?
• Is the genotoxicity seen with Croton palanostigma sap in mice shared by Croton lechleri sap?
• Which constituent is responsible for wound effects in animals: taspine, the proanthocyanidins, or both?
• What does long-term use of crofelemer look like? A 2013 review noted that long-term safety data were lacking.

Key Research: Crofelemer, the Drug

The mechanism study, the phase 3 approval trial, the negative IBS trial, the chemotherapy-diarrhoea trial, and the independent reviews of the approval.

1. Tradtrantip L, Namkung W, Verkman AS. Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Molecular pharmacology. 2010;77(1):69-78. PubMed PMID: 19808995
2. Macarthur RD, Hawkins TN, Brown SJ, et al. Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two-stage study. HIV clinical trials. 2013;14(6):261-73. PubMed PMID: 24334179
3. Frampton JE. Crofelemer: a review of its use in the management of non-infectious diarrhoea in adult patients with HIV/AIDS on antiretroviral therapy. Drugs. 2013;73(10):1121-9. PubMed PMID: 23807722
4. Yeo QM, Crutchley R, Cottreau J, et al. Crofelemer, a novel antisecretory agent approved for the treatment of HIV-associated diarrhea. Drugs of today (Barcelona, Spain : 1998). 2013;49(4):239-52. PubMed PMID: 23616951
5. Patel TS, Crutchley RD, Tucker AM, et al. Crofelemer for the treatment of chronic diarrhea in patients living with HIV/AIDS. HIV/AIDS (Auckland, N.Z.). 2013;5:153-62. PubMed PMID: 23888120
6. Chordia P, MacArthur RD. Crofelemer, a novel agent for treatment of non-infectious diarrhea in HIV-infected persons. Expert review of gastroenterology & hepatology. 2013;7(7):591-600. PubMed PMID: 24070150
7. Castro JG, Chin-Beckford N. Crofelemer for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on anti-retroviral therapy. Expert review of clinical pharmacology. 2015;8(6):683-90. PubMed PMID: 26517110
8. Mangel AW, Chaturvedi P. Evaluation of crofelemer in the treatment of diarrhea-predominant irritable bowel syndrome patients. Digestion. 2008;78(4):180-6. PubMed PMID: 19092244
9. Pohlmann PR, Graham D, Wu T, et al. HALT-D: a randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane. Breast cancer research and treatment. 2022;196(3):571-581. PubMed PMID: 36280642
10. Kleindl PA, Xiong J, Hewarathna A, et al. The Botanical Drug Substance Crofelemer as a Model System for Comparative Characterization of Complex Mixture Drugs. Journal of pharmaceutical sciences. 2017;106(11):3242-3256. PubMed PMID: 28743606
11. Crofelemer. 2012;. PubMed PMID: 31643647
12. Logan C, Beadsworth MB, Beeching NJ. HIV and diarrhoea: what is new? Current opinion in infectious diseases. 2016;29(5):486-94. PubMed PMID: 27472290

Key Research: Wounds, Skin and Inflammation

Reviews of the traditional uses and the laboratory work on inflammation and immunity. The pressure-ulcer meta-analysis is included because it is often cited for "dragon's blood", but it concerns the Chinese resin.

1. Jones K. Review of sangre de drago (Croton lechleri)--a South American tree sap in the treatment of diarrhea, inflammation, insect bites, viral infections, and wounds: traditional uses to clinical research. Journal of alternative and complementary medicine (New York, N.Y.). 2003;9(6):877-96. PubMed PMID: 14736360
2. Pona A, Cline A, Kolli SS, et al. Review of future insights of Dragon's Blood in dermatology. Dermatologic therapy. 2019;32(2):e12786. PubMed PMID: 30556246
3. de Albuquerque RDDG, León-Vargas FR, Carrasco-Montañez DD, et al. A Review on Phytochemistry and Recent Pharmacology of Dragon's Blood (Croton lechleri), a Multifunctional Ethnomedicinal Resource from the Amazon Forest. Planta medica. 2025;91(8):409-418. PubMed PMID: 40043740
4. Risco E, Ghia F, Vila R, et al. Immunomodulatory activity and chemical characterisation of sangre de drago (dragon's blood) from Croton lechleri. Planta medica. 2003;69(9):785-94. PubMed PMID: 14598201
5. Chen Z, Bertin R, Marin R, et al. Effects of Croton lechleri sap (Sangre de Drago) on AGEs formation, LDL oxidation and oxidative stress related to vascular diseases. Natural product research. 2022;36(16):4165-4169. PubMed PMID: 34338088
6. Mahboubi Kancha M, Mehrabi M, Aghaie F, et al. Preparation and characterization of PVA/chitosan nanofibers loaded with Dragon's blood or poly helixan as wound dressings. International journal of biological macromolecules. 2024;272(Pt 2):132844. PubMed PMID: 38834119
7. Nguyen JK, Masub N, Jagdeo J. Bioactive ingredients in Korean cosmeceuticals: Trends and research evidence. Journal of cosmetic dermatology. 2020;19(7):1555-1569. PubMed PMID: 32100931
8. Xu J, Xiong T, Yang Y, et al. Resina Draconis as a topical treatment for pressure ulcers: A systematic review and meta-analysis. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. 2015;23(4):565-74. PubMed PMID: 25968301

Key Research: Which Plant Is Which

1. Gupta D, Bleakley B, Gupta RK. Dragon's blood: botany, chemistry and therapeutic uses. Journal of ethnopharmacology. 2008;115(3):361-80. PubMed PMID: 18060708
2. Liu Y, Zhao X, Yao R, et al. Dragon's Blood from Dracaena Worldwide: Species, Traditional Uses, Phytochemistry and Pharmacology. The American journal of Chinese medicine. 2021;49(6):1315-1367. PubMed PMID: 34247562
3. Wu C, Cai XQ, Chang Y, et al. Rapid identification of dragon blood samples from Daemonorops draco, Dracaena cinnabari and Dracaena cochinchinensis by MALDI-TOF mass spectrometry. Phytochemical analysis : PCA. 2019;30(6):720-726. PubMed PMID: 31313432
4. Al-Awthan YS, Bahattab OS. Phytochemistry and Pharmacological Activities of Dracaena cinnabari Resin. BioMed research international. 2021;2021:8561696. PubMed PMID: 34337055
5. Al-Okaishi A. Exploring the historical distribution of Dracaena cinnabari using ethnobotanical knowledge on Socotra Island, Yemen. Journal of ethnobiology and ethnomedicine. 2021;17(1):22. PubMed PMID: 33794944
6. Mothana RA, Arbab AH, ElGamal AA, et al. Isolation and Characterization of Two Chalcone Derivatives with Anti-Hepatitis B Virus Activity from the Endemic Socotraen Dracaena cinnabari (Dragon's Blood Tree). Molecules (Basel, Switzerland). 2022;27(3). PubMed PMID: 35164217
7. Yang PX, Fan XX, Liu MX, et al. Longxuetongluo Capsule alleviate ischemia/reperfusion induced cardiomyocyte apoptosis through modulating oxidative stress and mitochondrial dysfunction. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024;134:155993. PubMed PMID: 39244943

Key Research: Taspine, Toxicity and Safety

1. Milanowski DJ, Winter RE, Elvin-Lewis MP, et al. Geographic distribution of three alkaloid chemotypes of Croton lechleri. Journal of natural products. 2002;65(6):814-9. PubMed PMID: 12088421
2. Montopoli M, Bertin R, Chen Z, et al. Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against human melanoma SK23 and colon cancer HT29 cell lines. Journal of ethnopharmacology. 2012;144(3):747-53. PubMed PMID: 23123266
3. Lopes MI, Saffi J, Echeverrigaray S, et al. Mutagenic and antioxidant activities of Croton lechleri sap in biological systems. Journal of ethnopharmacology. 2004;95(2-3):437-45. PubMed PMID: 15507372
4. Maistro EL, Ganthous G, Machado Mda S, et al. Dragon's blood Croton palanostigma induces genotoxic effects in mice. Journal of ethnopharmacology. 2013;147(2):406-11. PubMed PMID: 23528364
5. Alonso-Castro AJ, Ortiz-Sánchez E, Domínguez F, et al. Antitumor effect of Croton lechleri Mull. Arg. (Euphorbiaceae). Journal of ethnopharmacology. 2012;140(2):438-42. PubMed PMID: 22301443
6. Froldi G, Zagotto G, Filippini R, et al. Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2009;16(8):768-75. PubMed PMID: 19406630
7. Zhang Y, He L, Meng L, et al. Suppression of tumor-induced angiogenesis by taspine isolated from Radix et Rhizoma Leonticis and its mechanism of action in vitro. Cancer letters. 2008;262(1):103-13. PubMed PMID: 18180095
8. Tzintzarov A, Boyadzhieva SS, Coelho JAP, et al. Novel Insights into the Biological Activity of Croton lechleri Twigs Extracts and Advancements in Their Sustainable Recovery. Molecules (Basel, Switzerland). 2024;29(17). PubMed PMID: 39275010

PubMed Topic Searches

1. PubMed: Croton lechleri toxicity
2. PubMed: Taspine cytotoxicity
3. PubMed: Crofelemer safety
4. PubMed: Croton dragon's blood clinical trials

External Resources

• LiverTox: Crofelemer — the US National Library of Medicine's liver-safety entry for the drug.
• PubMed — the biomedical literature database behind every citation on these pages.
• ClinicalTrials.gov — the trials registry, where crofelemer studies and any trial of the crude sap would be listed.
• National Center for Complementary and Integrative Health — plain-language summaries of herbs and supplements.
• Plants of the World Online (Kew) — authoritative botanical names, useful for separating Croton, Dracaena and Daemonorops.

Connections

• All Herbs
• Dragon's Blood (Croton lechleri) — the main topic page
• Skin, Wound and Topical Herbs — the parent category
• Crofelemer: From Sap to Licensed Drug — the approved drug
• Wound Healing and Insect Bites — the traditional skin uses
• Four Plants, One Name — which resin is which
• Taspine, Toxicity and Safety Unknowns — the safety findings
• HIV/AIDS — the condition behind the drug's approval
• Chronic Diarrhea — causes and evaluation
• Irritable Bowel Syndrome — the negative crofelemer trial
• Grape Seed Extract — proanthocyanidins from another source
• French Maritime Pine Bark — another proanthocyanidin-rich bark
• Comfrey — another wound herb with an internal safety concern
• Calendula — a wound herb with more human trial data

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