Croton lechleri

Purported Benefits, Side Effects & More

Croton lechleri

Purported Benefits, Side Effects & More
Croton lechleri

Common Names

  • Sangre de Drago
  • Dragon's Blood
  • Sangre de Grado
  • Sangre de Dragón
  • SP-303
  • Crofelemer

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Croton lechleri has not been shown to treat cancer in humans.

The dark red sap of C. lechleri, a tree found in many regions of South America, has been used in traditional medicine for wound healing and gastric ulcers. SP-303, a mixture of proanthocyanidin oligomers derived from the plant, was found effective in the treatment of traveler's diarrhea and diarrhea experienced by AIDS patients. Now known as crofelemer, it is has been approved by the FDA to treat AIDS-associated diarrhea.

Studies done in animals showed that C.lechleri reduced the size of gastric ulcers and also decreased the time required for wound healing, but human data are lacking. Laboratory studies indicate that it can kill cancer cells, but no studies have been done in humans.

What are the potential uses and benefits?
  • To treat diarrhea

    Clinical trials have shown that C. lechleri is effective for traveler's diarrhea and diarrhea experienced by AIDS patients.
  • To treat cancer

    Lab studies suggest that C. lechleri can kill cancer cells, but human data are lacking.
  • To treat viral infections

    One clinical trial found that topical C. lechleri was no more effective than placebo for recurrent genital herpes lesions in AIDS patients.
  • To treat gastric ulcers

    Animal studies suggest that C. lechleri may reduce the size of gastric ulcers, but studies have not been conducted in humans.
  • For wound healing

    There are no studies in humans that support this use, but animal studies suggest C. lechleri can decrease the time required for wound healing.
What else do I need to know?

Do Not Take if:

You are taking dacomitinib: Animal studies suggest crofelemer may worsen dacomitinib-induced diarrhea. Clinical relevance is not yet known.

For Healthcare Professionals

Scientific Name
Croton lechleri
Clinical Summary

Croton lechleri is a tree that is found in many regions of South America (1). Its dark red viscous latex, also known as Sangre de Grado or Dragon’s blood, has been used in traditional medicine for diarrhea and wound healing. In vitro and animal studies suggest it can promote the healing of gastric ulcers (8) and inhibit cutaneous neurogenic inflammation (15).

A mixture of proanthocyanidin oligomers isolated from the latex of C. lechleri has shown benefits for the treatment of travelers’ diarrhea (2) and diarrhea experienced by AIDS patients (3) (18). Named crofelemer, it has been approved by the FDA as a prescription drug to relieve diarrhea associated with antiretroviral therapy in AIDS patients (17). Supplementary analysis suggests it may also help reduce abdominal pain in women with irritable bowel syndrome with diarrhea (22). A clinical trial is underway to determine feasibility and tolerability of crofelemer for preventing diarrhea in breast cancer patients receiving trastuzumab, pertuzumab, and docetaxel or paclitaxel (THP), or trastuzumab, pertuzumab, docetaxel, and carboplatin (TCHP) (19).

In other studies, crofelemer was reported to be no more effective than placebo in AIDS patients with recurrent genital herpes  (14), while topical use of a cream containing C. lechleri resin and pomegranate seed oil was found useful in preventing and improving skin changes associated with dermal scarring (20).

C. lechleri demonstrated apoptotic effects in cancer cells (4). However, it also increased the viability of leukemic cells (5). Further research is needed to determine the anticancer potential.

Purported Uses and Benefits
  • Diarrhea
  • Cancer
  • Antiviral
  • Ulcers
  • Wound repair
Mechanism of Action

SP-303, a mixture of proanthocyanidin oligomers, inhibited cAMP-mediated chloride secretion in two intestinal epithelial cell lines (6) (7). The dual inhibitory action of crofelemer, a purified proanthocyanidin oligomer, on two structurally unrelated prosecretory intestinal Cl(-) channels may account for the intestinal antisecretory activity (16). The sap of C. lechleri also decreased capsaicin mediated chloride secretion (8) by inhibiting activation of sensory afferent nerves. In another study, it irreversibly altered the microtubule structure of cancer cells, preventing adhesion and inducing apoptosis (4). It also inhibited mutagenicity of 2-Aminoanthracene, although the mechanism is unknown (10). Topical application of Taspine, an alkaloid derived from C. lechleri sap, to a wound site produced an increase in wound healing activity (11) and an increase in the wound tensile strength 5-7 days following injury (12). Taspine promotes wound healing via increased migration of fibroblasts to the wound site (11) by acting as a chemotactic factor for fibroblasts (12).

  • Dacomitinib: Animal studies suggest crofelemer may worsen dacomitinib-induced diarrhea, although clinical relevance is not known (21).
  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. J Altern Complement Med 2003;9(6):877-96.
  2. 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;97(10):2585-8.
  3. Holodniy M, Koch J, Mistal M, 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. Am J Gastroenterol 1999;94(11):3267-73.
  4. Sandoval M, Okuhama NN, Clark M, et al. Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells. J Ethnopharmacol 2002;80(2-3):121-9.
  5. Styczynski J, Wysocki M. Alternative medicine remedies might stimulate viability of leukemic cells. Pediatr Blood Cancer 2006;46(1):94-8.
  6. Fischer H, Machen TE, Widdicombe JH, et al. A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells. J Ethnopharmacol 2004;93(2-3):351-7.
  7. Gabriel SE, Davenport SE, Steagall RJ, Vimal V, Carlson T, Rozhon EJ. A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion. Am J Physiol 1999;276(1 Pt 1):G58-63.
  8. Miller MJ, MacNaughton WK, Zhang XJ, et al. Treatment of gastric ulcers and diarrhea with the Amazonian herbal medicine sangre de grado. Am J Physiol Gastrointest Liver Physiol 2000;279(1):G192-200.
  9. Miller MJ, Vergnolle N, McKnight W, et al. Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado. J Invest Dermatol 2001;117(3):725-30.
  10. Rossi D, Bruni R, Bianchi N, et al. Evaluation of the mutagenic, antimutagenic and antiproliferative potential of Croton lechleri (Muell. Arg.) latex. Phytomedicine 2003;10(2-3):139-44.
  11. Vaisberg AJ, Milla M, Planas MC, et al. Taspine is the cicatrizant principle in Sangre de Grado extracted from Croton lechleri. Planta Med 1989;55(2):140-3.
  12. Porras-Reyes BH, Lewis WH, Roman J, Simchowitz L, Mustoe TA. Enhancement of wound healing by the alkaloid taspine defining mechanism of action. Proc Soc Exp Biol Med 1993;203(1):18-25.
  13. Chen ZP, Cai Y, Phillipson JD. Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon’s blood. Planta Med 1994;60(6):541-5.
  14. Orozco-Topete R, Sierra-Madero J, Cano-Dominguez C, et al. Safety and efficacy of Virend for topical treatment of genital and anal herpes simplex lesions in patients with AIDS. Antiviral Res 1997;35(2):91-103.
  15. Pereira U, Garcia-Le Gal C, Le Gal G, et al. Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation. Exp Dermatol. 2010 Sep;19(9):796-9.
  16. Tradtrantip L, Namkung W, Verkman AS. Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels.Mol Pharmacol. 2010 Jan;77(1):69-78.
  17. FDA approves first anti-diarrheal drug for HIV/AIDS patients. US Food and Drug Administration; August 14, 2017. Accessed February 9, 2021.
  18. 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 Clin Trials. 2013 Nov-Dec;14(6):261-73.
  19. Gao JJ, Tan M, Pohlmann PR, Swain SM. HALT-D: A Phase II Evaluation of Crofelemer for the Prevention and Prophylaxis of Diarrhea in Patients With Breast Cancer on Pertuzumab-Based Regimens. Clin Breast Cancer. 2017 Feb;17(1):76-78.
  20. Bogdan C, Iurian S, Tomuta I, Moldovan M. Improvement of skin condition in striae distensae: development, characterization and clinical efficacy of a cosmetic product containing Punica granatum seed oil and Croton lechleri resin extract. Drug Des Devel Ther. 2017 Feb 24;11:521-531.
  21. Van Sebille YZA, Gibson RJ, Wardill HR, Ball IA, Keefe DMK, Bowen JM. Dacomitinib-induced diarrhea: Targeting chloride secretion with crofelemer. Int J Cancer. 2018 Jan 15;142(2):369-380.
  22. Nee J, Salley K, Ludwig AG, et al. Randomized Clinical Trial: Crofelemer Treatment in Women With Diarrhea-Predominant Irritable Bowel Syndrome. Clin Transl Gastroenterol. Dec 2019;10(12):e00110.
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