Download PDF
Planta Med
DOI: 10.1055/a-2551-5681
Reviews

A Review on Phytochemistry and Recent Pharmacology of Dragonʼs Blood (Croton lechleri), a Multifunctional Ethnomedicinal Resource from the Amazon Forest

Ricardo D.D.G. de Albuquerque
1   Laboratório de Tecnologia em Produtos Naturais, Universidade Federal Fluminense, Santa Rosa, Niterói, RJ, Brazil
,
Frank R. León-Vargas
2   Departamento de Ingeniería Química, Facultad de Ingeniería Química, Universidad Nacional de la Amazonia Peruana, Iquitos, Loreto, Peru
,
Daniel D. Carrasco-Montañez
2   Departamento de Ingeniería Química, Facultad de Ingeniería Química, Universidad Nacional de la Amazonia Peruana, Iquitos, Loreto, Peru
,
Jorge L. Carranza-Gonzales
3   Departamento de Ingeniería de Alimentos, Facultad de Industrias Alimentarias, Universidad Nacional de la Amazonia Peruana, Iquitos, Peru
,
Yessenia V.S. Ramos-Rivas
4   Departamento de Ciencias Clinicas Facultad de Medicina, Universidad Nacional de la Amazonia Peruana, Iquitos, Peru
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Croton lechleri, commonly known as “Sangre de Drago”, is a widely utilized ethnomedicinal resource in the Amazon region, known for its diverse bioactive properties. These include wound-healing activity, anti-inflammatory effects, antitumor activity, and other therapeutic benefits. 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 this species. Hence, this review is essential to inform researchers and readers about the current state of knowledge in this field. A systematic search was conducted using databases such as Scopus and Google Scholar, yielding 33 relevant articles focusing on the phytochemistry and recent pharmacological investigations of C. lechleri. These 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 pharmacological studies reviewed highlight several potential therapeutic effects of C. lechleri, particularly those associated with its resin. These effects include wound-healing, antitumor, anti-inflammatory, and gastrointestinal benefits, among others. The findings underscore the remarkable medicinal importance of this species, supporting its continued investigation and potential therapeutic applications.

Keywords

Sangre de Drago - Croton lechleri - Euphorbiaceae - phytochemicals - biological activities - natural resources


Publication History

Received: 02 November 2024

Accepted after revision: 05 March 2025

Accepted Manuscript online:
05 March 2025

Article published online:
20 March 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Peres IS, Conceição KA, Silva LA, Khouri NG, Yoshida CM, Concha VO, Lucarini M, Durazzo A, Santini A, Souto EB, Severino P. Dragonʼs blood: Antioxidant properties for nutraceuticals and pharmaceuticals. Rendiconti Lincei Sci Fis Nat 2023; 34: 131-142
    CrossrefPubMedSearch in Google Scholar
  • 2 Napagoda M, Wijesundara D. Medicinal plants as sources of novel therapeutics: The history, present, and future. Chem Nat Prod Phytochem Pharm Med Plants 2022; 3: 4-18
    PubMedSearch in Google Scholar
  • 3 Choudhary SS, Verma S. A comprehensive review on patents, herbal treatment and clinical trials on acquired immune deficiency syndrome. Infect Disord Drug Targets 2024; 24: 70-81
    CrossrefPubMedSearch in Google Scholar
  • 4 Forero E, Chavez R, Bernal HY. Agrotecnología para el cultivo de sangre de grado o sangregrado. In: Martínez JV, Bernal HJ, Cáceres A. Fundamentos de agrotecnología para el cultivo de plantas medicinais Iberoamericanas. Santafé de Bogotá: Convenio Andrés Bello, Ciencia y Tecnología para el Desarrollo; 2000: 57-190
    Search in Google Scholar
  • 5 De Marino S, Gala F, Zollo F, Vitalini S, Fico G, Visioli F, Iorizzi M. Identification of minor secondary metabolites from the latex of Croton lechleri (Muell-Arg) and evaluation of their antioxidant activity. Molecules 2008; 13: 1219-1229
    CrossrefPubMedSearch in Google Scholar
  • 6 King S, Martin M, Fonseca R, Fonseca M, Diaz C, Valles K. Sustainable harvesting of dragonʼs blood (Croton lechleri) in Peru. Herb Gram 2020; 125: 44-57
    PubMedSearch in Google Scholar
  • 7 Cevallos-Morillo C, Cisneros-Pérez P, Llive R, Ricaurte M, Reinoso C, Meneses MA, Guamán MC, Palma-Cando A. Croton lechleri extracts as green corrosion inhibitors of admiralty brass in hydrochloric acid. Molecules 2021; 26: 7417
    CrossrefPubMedSearch in Google Scholar
  • 8 Cai Y, Evans FJ, Roberts MF, Phillipson JD, Zenk MH, Gleba YY. Polyphenolic compounds from Croton lechleri . Phytochem 1991; 30: 2033-2040
    CrossrefPubMedSearch in Google Scholar
  • 9 Ubillas R, Jolad SD, Bruening RC, Kernan MR, King SR, Sesin DF, Barrett M, Stoddart CA, Flaster T, Kuo J, Ayala F, Meza E, Castañel M, Mcmeekin D, Rozhon E, Tempesta MS, Barnard D, Huffman J, Smee D, Sidwell R, Nakanishi K. SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago). Phytomedicine 1994; 1: 77-106
    CrossrefPubMedSearch in Google Scholar
  • 10 Fischer H, Machen TE, Widdicombe JH, Carlson TJ, King SR, Chow JW, Illek B. 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: 351-357
    CrossrefPubMedSearch in Google Scholar
  • 11 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; 77: 69-78
    CrossrefPubMedSearch in Google Scholar
  • 12 Cai Y, Chen ZP, Phillipson JD. Diterpenes from Croton lechleri . Phytochem 1993; 32: 755-760
    CrossrefPubMedSearch in Google Scholar
  • 13 Chen ZP, Cai Y, Phillipson JD. Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragonʼs blood. Planta Med 1994; 60: 541-545
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Alonso-Castro AJ, Ortiz-Sánchez E, Domínguez F, López-Toledo G, Chávez M, Ortiz-Tello AJ, García-Carrancá A. Antitumor effect of Croton lechleri mull. arg.(Euphorbiaceae). J Ethnopharmacol 2012; 140: 438-442
    CrossrefPubMedSearch in Google Scholar
  • 15 Tzintzarov A, Boyadzhieva SS, Coelho JA, Tsvetanova F, Petrova M, Stoev G, Yankov DS, Ugrinova I, Stateva RP. Novel insights into the biological activity of croton lechleri twigs extracts and advancements in their sustainable recovery. Molecules 2024; 29: 4171
    CrossrefPubMedSearch in Google Scholar
  • 16 Diedrich C, da Silva LD, Sari R, de Cristo Borges GC, Muniz HS, de Lima VA, Oldoni TLC, Carpes ST. Bioactive compounds extraction of Croton lechleri barks from Amazon forest using chemometrics tools. J King Saudi Univ Sci 2021; 33: 101416
    CrossrefPubMedSearch in Google Scholar
  • 17 Milanowski DJ, Winter RE, Elvin-Lewis MP, Lewis WH. Geographic distribution of three alkaloid chemotypes of croton lechleri . J Nat Prod 2002; 65: 814-819
    CrossrefPubMedSearch in Google Scholar
  • 18 Carlín L, Vaisberg AJ, Hammond GB. Isolation of sinoacutine from the leaves of Croton lechleri . Planta Med 1996; 62: 90-91
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Pieters L. La sangre de drago: Una droga tradicional de Sudamérica: Constituyentes biológicamente activos active biological. 1st Edition. Quito: Abya-Yala; 1998: 13-202
    Search in Google Scholar
  • 20 Bettolo RM, Scarpati ML. Alkaloids of Croton draconoides . Phytochem 1979; 18: 9-11
    CrossrefPubMedSearch in Google Scholar
  • 21 Rossi D, Guerrini A, Maietti S, Bruni R, Paganetto G, Poli F, Sacchetti G. Chemical fingerprinting and bioactivity of Amazonian Ecuador Croton lechleri Müll. Arg.(Euphorbiaceae) stem bark essential oil: A new functional food ingredient?. Food Chem 2011; 126: 837-848
    CrossrefPubMedSearch in Google Scholar
  • 22 Rempel C, Zagonel FD, da Silva DS, Marmitt DJ, Sehnem E. Effect of the cream based on Croton lechleri Müll. Arg. in the treatment of diabetic patientsʼ ulcers: A case study. Cadernos UniFOA 2020; 15: 44
    CrossrefPubMedSearch in Google Scholar
  • 23 Risco E, Ghia F, Vila R, Iglesias J, Álvarez E, Cañigueral S. Immunomodulatory activity and chemical characterisation of sangre de drago (Dragonʼs blood) from Croton lechleri . Planta Med 2003; 69: 785-794
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Namjoyan F, Kiashi F, Moosavi ZB, Saffari F, Makhmalzadeh BS. Efficacy of dragonʼs blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial. J Tradit Complement Med 2016; 6: 37-40
    CrossrefPubMedSearch in Google Scholar
  • 25 Monterubbianesi R, Sarri S, Memè L, Orsini G, Sparabombe S. Combining the non-surgical treatment with extracts of Croton Lechleri and Myrciaria Dubia to solve gingival cleft. Appl Sci 2023; 13: 1735
    CrossrefPubMedSearch in Google Scholar
  • 26 Wang W, Olson D, Cheng B, Guo X, Wang K. Sanguis Draconis resin stimulates osteoblast alkaline phosphatase activity and mineralization in MC3 T3-E1 cells. J Ethnopharmacol 2012; 142: 168-174
    CrossrefPubMedSearch in Google Scholar
  • 27 Rossi D, Bruni R, Bianchi N, Chiarabelli C, Gambari R, Medici A, Lista A, Paganetto G. Evaluation of the mutagenic, antimutagenic and antiproliferative potential of Croton lechleri (Muell. Arg.) latex. Phytomedicine 2003; 10: 139-144
    CrossrefPubMedSearch in Google Scholar
  • 28 Montopoli M, Bertin R, Chen Z, Bolcato J, Caparrotta L, Froldi G. Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against human melanoma SK23 and colon cancer HT29 cell lines. J Ethnopharmacol 2012; 144: 747-753
    CrossrefPubMedSearch in Google Scholar
  • 29 Hess C. The Effect of the Peruvian Plant Extract, Croton lechleri (Dragonʼs Blood) on PC3 Prostate Tumor Cell Apoptosis [Dissertation]. Rock Hill: Winthrop University; 2018
    Search in Google Scholar
  • 30 Rossi D, Guerrini A, Paganetto G, Bernacchia G, Conforti F, Statti G, Maietti S, Poppi I, Tacchini M, Sacchetti G. Croton lechleri Müll. Arg.(Euphorbiaceae) stem bark essential oil as possible mutagen-protective food ingredient against heterocyclic amines from cooked food. Food Chem 2013; 139: 439-447
    CrossrefPubMedSearch in Google Scholar
  • 31 Tamariz Ortiz JH, Capcha Mendoza R, Palomino Chains EJ, Aguilar Olano J. Antibacterial activity of dragonʼs blood (Croton lechleri) against Helicobacter pylori . Accessed October 23, 2016 at: https://crotonlechleri.wordpress.com/2016/04/03/antibacterial-activity-of-dragons-blood-croton-lechleri-%25e2%2580%258b%25e2%2580%258b-against-helicobacter-pylori/
    PubMed
  • 32 Corrales Ramírez L, Castillo-Castañeda A, Melo Vargas A. In vitro evaluation of antibacterial potential of Croton lechleri against bacterial isolates from patients with skin ulcers. Nova 2013; 11: 51-63
    PubMedSearch in Google Scholar
  • 33 Guevara CB, Montaluisa L, Rodriguez MEM. The antimicrobial activity of alcoholic extracts of leaves and bark from two varieties of “Sangre de Drago” compared with the antibacterial activity present in the latex of the same species. F1000Res 2018; 7: 2020
    CrossrefPubMedSearch in Google Scholar
  • 34 dos Santos APA, Pacheco SGA, Teles CBG. Efeito leishmanicida in vitro do látex de Croton lechleri (Euphorbiaceae). Rev Cien Farm Bas Apl 2015; 36: 413-418
    PubMedSearch in Google Scholar
  • 35 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; 11: 521-531
    CrossrefPubMedSearch in Google Scholar
  • 36 Desmarchelier C, Schaus FW, Coussio J, Cicca G. Effects of sangre de drago from Croton lechleri Muell.-Arg. on the production of active oxygen radicals. J Ethnopharmacol 1997; 58: 103-108
    CrossrefPubMedSearch in Google Scholar
  • 37 Lopes MI, Saffi J, Echeverrigaray S, Henriques JAP, Salvador M. Mutagenic and antioxidant activities of Croton lechleri sap in biological systems. J Ethnopharmacol 2004; 95: 437-445
    CrossrefPubMedSearch in Google Scholar
  • 38 Froldi G, Zagotto G, Filippini R, Montopoli M, Dorigo P, Caparrotta L. Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles. Phytomedicine 2009; 16: 768-775
    CrossrefPubMedSearch in Google Scholar
  • 39 Chen Z, Bertin R, Marin R, Medjiofack Djeujo F, Froldi G. Effects of Croton lechleri sap (Sangre de Drago) on AGEs formation, LDL oxidation and oxidative stress related to vascular diseases. Nat Prod Res 2022; 36: 4165-4169
    CrossrefPubMedSearch in Google Scholar
  • 40 Vaisberg AJ, Milla M, Planas MC, Cordova JL, de Agusti ER, Ferreyra R, Mustiga MC, Carlín L, Hammond GB. Taspine is the cicatrizant principle in Sangre de Grado extracted from Croton lechleri . Planta Med 1989; 55: 140-143
    Thieme ConnectPubMedSearch in Google Scholar
  • 41 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: 18-25
    CrossrefPubMedSearch in Google Scholar
  • 42 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 Gastrointest Liver Physiol 1999; 276: G58-G63
    CrossrefPubMedSearch in Google Scholar
  • 43 Perdue GP, Blomster RN, Blake DA, Farnsworth NR. South American plants II: Taspine isolation and anti‐inflammatory activity. J Pharm Sci 1979; 68: 124-126
    CrossrefPubMedSearch in Google Scholar
  • 44 Barnard DL, Smee DF, Huffman JH, Meyerson LR, Sidwell RW. Antiherpesvirus activity and mode of action of SP-303, a novel plant flavonoid. Chemotherapy 1993; 39: 203-211
    CrossrefPubMedSearch in Google Scholar
  • 45 Safrin S, Phan L, Elbeik T. Evaluation of the in vitro activity of SP-303 against clinical isolates of acyclovir-resistant and foscarnet-resistant herpes simplex virus [abstract 136]. Antiviral Res 1993; 20: 117
    CrossrefPubMedSearch in Google Scholar
  • 46 Gilbert BE, Wyde PR, Wilson PZ, Meyerson L. SP-303 small particle aerosol treatment of influenza A virus infection in mice and respiratory syncytial virus infection in cotton rats. Antiviral Res 1993; 21: 37-45
    CrossrefPubMedSearch in Google Scholar
  • 47 Wyde PR, Meyerson LR, Ambrose MW, Pfeifer JP, Voss TG, Gilbert BE. Elucidation of a polyphenolic polymer with antiviral activity against myxo- and paramyxoviruses [abstract 45]. Antiviral Res 1991; 15: 67
    CrossrefPubMedSearch in Google Scholar
  • 48 Barnard DL, Huffman JH, Nelson RM, Morris JLB, Gessaman AC, Sidwell RW, Meyerson LR. Mode of action of SP-303 against respiratory syncytial virus (RSV) [abstract 176]. Antiviral Res 1992; 17 (Suppl. 1) 138
    PubMedSearch in Google Scholar
  • 49 Wyde PR, Ambrose MW, Meyerson LR, Gilbert BE. The antiviral activity of SP 303, a natural polyphenolic polymer, against respiratory syncytial and parainfluenza type 3 viruses in cotton rats. Antiviral Res 1993; 20: 145-154
    CrossrefPubMedSearch in Google Scholar
  • 50 Soike KF, Zhang JY, Meyerson LR. Reduction of respiratory syncytial virus (RSV) shedding in African green monkeys treated with SP303 [abstract 89]. Antiviral Res 1992; 91 (Suppl. 1) 91
    PubMedSearch in Google Scholar
  • 51 Sethi ML. Inhibition of RNA-directed DNA polymerase activity of RNA tumor viruses by taspine. Canadian J Pharm Sci 1977; 12: 7-9
    PubMedSearch in Google Scholar
  • 52 Koch J, Tuveson J, Carlson T, Schmidt J. A new therapy for HIV-associated diarrhea improves quality of life. Seventh European Conference on Clinical Aspects and Treatment of HIV-Infection. Lisbon, Portugal; October 23 – 27, 1999.
    PubMed
  • 53 Orozco-Topete R, Sierra-Madero J, Cano-Dominguez C, Kershenovich J, Ortiz-Pedroza G, Vasquez-Valls E, Garcia-Cosio C, Soria-Cordoba A, Armendariz AM, Teran-Toledo X, Romo-Garcia J, Fernandez H, Rozhon EJ. Safety and efficacy of Virend for topical treatment of genital and anal herpes simplex lesions in patients with AIDS. Antiviral Res 1997; 35: 91-103
    CrossrefPubMedSearch in Google Scholar
  • 54 Miller MJS, Vergnolle N, McKnight W, Musah RA, Davison CA, Trentacosti AM, Thompson JH, Sandoval M, Wallace JL. Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado. J Invest Dermatol 2001; 117: 725-730
    CrossrefPubMedSearch in Google Scholar
  • 55 de Albuquerque RDDG. Plants as auxiliaries in the healing process: Mechanisms of action, formulations and indications. Med Plant Comm 2018; 1: 9-12
    PubMedSearch in Google Scholar
  • 56 Salatino A, Salatino MLF, Negri G. Traditional uses, chemistry and pharmacology of Croton species (Euphorbiaceae). J Braz Chem Soc 2007; 18: 11-33
    CrossrefPubMedSearch in Google Scholar
  • 57 Bergemalm D, Andersson E, Hultdin J, Eriksson C, Rush ST, Kalla R, Halfvarson J. Systemic inflammation in preclinical ulcerative colitis. Gastroenterol 2021; 161: 1526-1539
    CrossrefPubMedSearch in Google Scholar
  • 58 Ciciliato MP, de Souza MC, Tarran CM, de Castilho ALT, Vieira AJ, Rozza AL. Anti-inflammatory effect of vanillin protects the stomach against ulcer formation. Pharmaceutics 2022; 14: 755
    CrossrefPubMedSearch in Google Scholar