Croton lechleri

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Croton lechleri
Sangre de Grado.jpg
Scientific classification OOjs UI icon edit-ltr.svg
Kingdom: Plantae
Clade: Tracheophytes
Clade: Angiosperms
Clade: Eudicots
Clade: Rosids
Order: Malpighiales
Family: Euphorbiaceae
Genus: Croton
Species:
C. lechleri
Binomial name
Croton lechleri

Croton lechleri is a species of flowering plant in the spurge family, Euphorbiaceae, that is native to northwestern South America. It is commonly known as sangre de grado (Peruvian Spanish), sangre de drago (Ecuadorian Spanish) or sangre de grada (Bolivian Spanish) . [2] They refer to this tree's (and several related species') thick red latex. [2] [3]

Contents

The latex has medicinal properties, and is used by local peoples as a liquid bandage, applied to seal wounds, as it dries quickly to form a protective skin-like barrier. [4] Its use by native people has led to scientific study and observation of its in vitro antioxidant activity as well as both mutagenic [5] and antimutagenic [6] behavior.

The latex also contains a number of chemicals, including taspine. [7] Oligomeric proanthocyanidins, another kind of chemical contained in the latex, have been investigated for the treatment of HIV-associated diarrhea under the name crofelemer. [8] In January 2013, crofelemer, under the trade name Mytesi, was approved by the FDA for the treatment of non-infectious diarrhea in HIV+ patients. [9]

Description

Croton lechleri belongs to the family Euphorbiaceae and are medium-sized trees with evergreen foliage, growing 10 to 20 meters (30 to 60 feet) in height. [4] Despite their relatively large height, the trees have very narrow trunks, averaging a bole diameter of about 30 centimeters (1 ft). [3] The leaves are large, alternate cordate (heart-shaped), bright green and 15–30 cm in width and length. [10] The flowers are greenish-white, white or amber, which produce small, three-part capsule fruits that appear on a thin spike that measures 30–50 cm. [4] [10] Both the smooth, mottled bark and viscous, red, latex-rich resin excreted from the wounded trunk of the tree are used medicinally.[9] While the sap can be harvested with a tap much like natural latex from rubber trees, trees that are repeatedly tapped become vulnerable to fungal infections. [5]

Croton lechleri are native to the Amazon basin and are distributed across the tropical regions of the South American countries of Bolivia, Brazil, Colombia, Ecuador, Peru, and Venezuela. [4] [11] They are most commonly found in the northwest lowlands between sea level up to 1000 m in elevation, mostly in mineral-rich disturbed soil and along rivers. [4] [10]

History

The earliest written reference to Croton lechleri dates to the 17th century, when Spanish Jesuit missionary, naturalist, and explorer, Bernabé Cobo encountered the use of the plant's resin by indigenous tribes throughout Mexico, Peru and Ecuador. [11] This discovery was greatly overshadowed in Europe by his description of cinchona bark, or Jesuit's bark, which was instrumental in the discovery and isolation of quinine.

Medicinal Use

Traditional Medicine

The resin of Croton lechleri, commonly known as sangre de drago, has a long history of medicinal use by indigenous peoples and is widely used in both urban and rural contexts in Peru and Ecuador, and to a lesser extent in other endemic countries.[8] For centuries, the sap has been used to cover abrasions, cuts, scratches, blisters, bites and stings to prevent bleeding, decrease inflammation, seal wounds and injuries to protect from infection. [4] [12] The sap dries quickly on soft, damaged tissue, forming a barrier similar in thickness to the skin removed, noted as something akin to a "second skin." [12] Antimicrobial activity offered by the plant is further believed to offer protection to the injury. [13] The formation of this resistant barrier is likely due to the saps ability to co-precipitate with surrounding proteins or extracellular matrix elements. [4] The hemostatic qualities relevant in wound healing that are associated with sangre de grado are further relevant to Amazonian indigenous communities in arresting the large amounts of bleeding following childbirth. [4] Beyond cutaneous ailments, the use of sangre de grado is taken orally for gastrointestinal disorders and irregularities including gastritis, gastric ulcers, intestinal infections, and inflammation. [4]

Modern Use and Clinical Research

Wound Care

Recent studies confirm the biochemical role played by the chemical composition of sangre de grado as a cicatrizant beneficial in the reduction of mean wound healing time. [14] [15] [16] The polyphenolic compounds of the sap further create a protective layer at the wound surface, preventing the entry of pathogenic microbes. These compounds condense and bind to surrounding extracellular proteins, clogging the wound and offering vasoconstriction at the site of injury, which is crucial in wound healing. [13] Taspine was found to be the principal cicatrizant agent in murine models as well as able to increase the chemotaxis of human fibroblast cells which is the most likely mechanism by which the resin and taspine accelerate the wound healing process. [17] The chemotaxis of fibroblasts aids the reformation in the reformation of the matrix following re-epithelialization, allowing for the regeneration of damaged skin. [14]

Antimicrobial Activity

Some compounds of the resin, as found in a particular study, 2,4,6-trimethoxyphenol, 1,3,5-trimethoxybenzene, crolechinic acid, and korberins A and B showed exhibited antibacterial properties individually. [14] Sangre de grado from the closely related Croton urucurana was reported to exhibit antifungal qualities due to the presence of catechins and epigallocatechin contained in the resin, both of which are also found in Croton lechleri. In one study, disk diffusion method proved concentration-dependent antifungal activity against Trichophyton , Microsporum and Epidermophyton , three of the most common species of dermatophytes that cause superficial fungal infections of human skin. [16] Further research is needed, however, to examine the role of sangre de grado from Croton lechleri as an effective antifungal agent in animal and human models.

Antiviral activity against influenza, parainfluenza, Herpes simplex viruses I and II, and Hepatitis A and B by Croton lechleri extracts and compounds have been exhibited. [13] [18] [19] [20] The most notable compound involved in antiviral activity is SP-303, also known as crofelemer, which has been heavily studied in vitro for its antiviral activity against the aforementioned viruses, as well as thymidine kinase mutants of HSV-1 and HSV-2 and acyclovir-resistant strains. [18] [21]

Antidiarrhoeal Activity

Crofelemer, a purified proanthocyanidin oligomer extracted from the sap of Croton lechleri has been investigated for potential antidiarrhoeal activity. Various clinical studies have confirmed significant improvement in acute E. coli and V. cholera diarrhea cases from the administration of crofelemer. [22] [23] In the context of the principal luminal membrane determinants of intestinal fluid secretion, the mechanism of crofelemer action involves the inhibition of apical membrane cAMP-stimulated (CFTR) and calcium-stimulated (CaCC) Cl− channels by crofelemer molecules, with little effect on cation channels or cAMP/calcium signaling. [24] As a result, fewer chloride ions are excreted into the bowel, decreasing the excretion of sodium ions and water, improving stool consistency and preventing diarrhea. [24]

Up to 90% of individuals living with HIV face HIV-associated diarrhea, largely caused as a side effect of antiretroviral drugs such as nucleoside analog reverse transcriptase inhibitors and protease inhibitors, which worsens with an increasingly compromised immune system. [10] Various clinical have emphasized statistically significant efficacy crofelemer in HIV-associated diarrhea and restoration of digestive regularity. [10] In 2012, a Phase III clinical trial for diarrhea in HIV patients was completed, and the drug was approved US Food and Drug Administration (FDA) the following year under the trade name Mytesi. [9] [10]

Chemistry

Proanthocyanidins are the main constituent of the resin produced by Croton lechleri, constituting more than 90% of its dry weight. [25] The remaining 10% is largely alkaloid taspine, as well as catechin, epigallocatechin, epicatechin, and low amounts of terpene compounds. [25]

Related Research Articles

<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.

An antiseptic is an antimicrobial substance or compound that is applied to living tissue to reduce the possibility of sepsis, infection or putrefaction. Antiseptics are generally distinguished from antibiotics by the latter's ability to safely destroy bacteria within the body, and from disinfectants, which destroy microorganisms found on non-living objects.

<span class="mw-page-title-main">Dragon's blood</span> Bright red plant-based resin

Dragon's blood is a bright red resin which is obtained from different species of a number of distinct plant genera: Calamus spp. also including Calamus rotang, Croton, Dracaena and Pterocarpus. The red resin has been in continuous use since ancient times as varnish, medicine, incense, pigment, and dye.

<span class="mw-page-title-main">Exudate</span> Fluid emitted through pores or a wound

An exudate is a fluid released by an organism through pores or a wound, a process known as exuding or exudation. Exudate is derived from exude 'to ooze' from Latin exsūdāre 'to sweat'.

An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.

<span class="mw-page-title-main">Ajoene</span> Chemical compound

Ajoene is an organosulfur compound found in garlic (Allium sativum) extracts. It is a colorless liquid that contains sulfoxide and disulfide functional groups. The name (and pronunciation) is derived from "ajo", the Spanish word for garlic. It is found as a mixture of up to four stereoisomers, which differ in terms of the stereochemistry of the central alkene (E- vs Z-) and the chirality of the sulfoxide sulfur (R- vs S-).

<i>Croton</i> (plant) Genus of flowering plants

Croton is an extensive plant genus in the spurge family, Euphorbiaceae. The plants of this genus were described and introduced to Europeans by Georg Eberhard Rumphius. The common names for this genus are rushfoil and croton, but the latter also refers to Codiaeum variegatum. The generic name comes from the Greek κρότος, which means "tick" and refers to the shape of the seeds of certain species.

<i>Calotropis</i> Genus of flowering plants

Calotropis is a genus of flowering plants in the family Apocynaceae, first described as a genus in 1810. It is native to southern Asia and North Africa.

Proanthocyanidins are a class of polyphenols found in many plants, such as cranberry, blueberry, and grape seeds. Chemically, they are oligomeric flavonoids. Many are oligomers of catechin and epicatechin and their gallic acid esters. More complex polyphenols, having the same polymeric building block, form the group of tannins.

<span class="mw-page-title-main">Procyanidin</span>

Procyanidins are members of the proanthocyanidin class of flavonoids. They are oligomeric compounds, formed from catechin and epicatechin molecules. They yield cyanidin when depolymerized under oxidative conditions.

<i>Euphorbia candelabrum</i> Species of flowering plant

Euphorbia candelabrum is a succulent species of plant in the family Euphorbiaceae, one of several plants commonly known as candelabra tree. It is endemic to the Horn of Africa and eastern Africa along the East African Rift system. It is known in Ethiopia by its Amharic name, qwolqwal, or its Oromo name, adaamii. It is closely related to three other species of Euphorbia: Euphorbia ingens in the dry regions of southern Africa, Euphorbia conspicua from western Angola, and Euphorbia abyssinica, which is native to countries including Sudan, Eritrea, Djibouti, Ethiopia and Somalia.

<span class="mw-page-title-main">Glaucine</span> Chemical compound

Glaucine(1,2,9,10-TetraMethoxyAporphine, Bromcholitin, Glauvent, Tusidil, Tussiglaucin) is an aporphine alkaloid found in several different plant species in the family Papaveraceae such as Glaucium flavum, Glaucium oxylobum and Corydalis yanhusuo, and in other plants like Croton lechleri in the family Euphorbiaceae.

<span class="mw-page-title-main">Prodelphinidin</span>

Prodelphinidin is a name for the polymeric tannins composed of gallocatechin. It yields delphinidin during depolymerisation under oxidative conditions.

<span class="mw-page-title-main">Hyperoside</span> Chemical compound

Hyperoside is a chemical compound. It is the 3-O-galactoside of quercetin.

Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs.

<span class="mw-page-title-main">Taspine</span> Chemical compound

Taspine is an alkaloid which acts as a potent acetylcholinesterase inhibitor and cicatrizant. It is found in various plants including Magnolia x soulangeana and Croton lechleri.

The ChemDB HIV, Opportunistic Infection and Tuberculosis Therapeutics Database is a publicly available tool developed by the National Institute of Allergy and Infectious Diseases to compile preclinical data on small molecules with potential therapeutic action against HIV/AIDS and related opportunistic infections.

<span class="mw-page-title-main">Crofelemer</span> Pharmaceutical drug

Crofelemer is an antidiarrheal indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Other possible uses include diarrhea in children, acute infectious diarrhea, and diarrhea in patients with irritable bowel syndrome. It is a purified oligomeric proanthocyanidin from "dragon's blood", the sap of the South American tree Croton lechleri.

<i>Plinia peruviana</i> Species of plant in the family Myrtaceae

Plinia peruviana, commonly known as jabuticaba cabinho in Brazil, is a species of plant in the family Myrtaceae. It is endemic to central, South America.

Croton grandilevus is a species of croton endemic to central and southern Brazil and to Paraguay.

References

  1. ↑ "Croton lechleri". Germplasm Resources Information Network . Agricultural Research Service, United States Department of Agriculture . Retrieved 2012-07-07.
  2. 1 2 Meza, E.N.(Editor). 1999.
  3. 1 2 "Database File for: Sangre de Grado (Croton lechleri)". Tropical Plant Database. Rainforest Database. Retrieved 2012-07-07.
  4. 1 2 3 4 5 6 7 8 9 Miller, Mark (2001). "Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado". Journal of Investigative Dermatology. 117 (3): 725–730. doi: 10.1046/j.0022-202x.2001.01446.x . PMID   11564183.
  5. 1 2 Lopes, M. I. L. E.; Saffi, J.; Echeverrigaray, S. R.; Henriques, J. O. A. P. G.; Salvador, M. (December 2004). "Mutagenic and antioxidant activities of Croton lechleri sap in biological systems". Journal of Ethnopharmacology. 95 (2–3): 437–445. doi:10.1016/j.jep.2004.08.025. PMID   15507372.
  6. ↑ Rossi, D.; Bruni, R.; Bianchi, N.; Chiarabelli, C.; Gambari, R.; Medici, A.; Lista, A.; Paganetto, G. (2003). "Evaluation of the mutagenic, antimutagenic and antiproliferative potential of Croton lechleri (Muell. Arg.) latex". Phytomedicine. 10 (2–3): 139–144. doi:10.1078/094471103321659843. hdl: 11392/532990 . PMID   12725567.
  7. ↑ Lopes, T. V.; Félix, S. R.; Schons, S. V.; Nobre, M. O. (January 2013). "Dragon's blood (Croton lechleri Mull., Arg.): an update on the chemical composition and medical applications of this natural plant extract. A review". Revista Brasileira de Higiene e Sanidade Animal. 7 (2): 167–191. doi: 10.5935/1981-2965.20130016 .
  8. ↑ Tradtrantip, L.; Namkung, W.; Verkman, A. S. (2009). "Crofelemer, an Antisecretory Antidiarrheal Proanthocyanidin Oligomer Extracted from Croton lechleri, Targets Two Distinct Intestinal Chloride Channels". Molecular Pharmacology. 77 (1): 69–78. doi:10.1124/mol.109.061051. PMC   2802429 . PMID   19808995.
  9. 1 2 "FDA approves first anti-diarrheal drug for HIV/AIDS patients". Food and Drug Administration. Dec 31, 2012.
  10. 1 2 3 4 5 6 Jones, Kenneth (December 2003). "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". The Journal of Alternative and Complementary Medicine. 9 (6): 877–896. doi:10.1089/107555303771952235. ISSN   1075-5535. PMID   14736360.
  11. 1 2 Cavalie Martel, Karina P.; Ortega Buitrón, Marisol R.; Bernardo Basilio, Yulith (2019-03-08). "Efectividad de la sangre de grado (croton lechleri) en la cicatrización de heridas post exodoncia en adultos". Investigación Valdizana. 13 (1): 7–14. doi: 10.33554/riv.13.1.167 . ISSN   1995-445X.
  12. 1 2 Taylor, Leslie (2005). The healing power of rainforest herbs: a guide to understanding and using herbal medicinals. Garden City Park, NY: Square One Publishers. ISBN   9780757001444. OCLC   690786708.
  13. 1 2 3 Chen, Z. P.; Cai, Y.; Phillipson, J. D. (December 1994). "Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon's blood". Planta Medica. 60 (6): 541–545. doi:10.1055/s-2006-959567. ISSN   0032-0943. PMID   7809208.
  14. 1 2 3 Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif (2015-01-22). "Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial". Journal of Traditional and Complementary Medicine. 6 (1): 37–40. doi:10.1016/j.jtcme.2014.11.029. ISSN   2225-4110. PMC   4737969 . PMID   26870678.
  15. ↑ Pieters, L.; De Bruyne, T.; Van Poel, B.; Vingerhoets, R.; Totté, J.; Vanden Berghe, D.; Vlietinck, A. (July 1995). "In vivo wound healing activity of Dragon's Blood (Croton spp.), a traditional South American drug, and its constituents". Phytomedicine. 2 (1): 17–22. doi:10.1016/S0944-7113(11)80043-7. ISSN   0944-7113. PMID   23196095.
  16. 1 2 Gurgel, Luilma A.; Sidrim, J. J. C.; Martins, Domingos T.; Filho, V. Cechinel; Rao, Vietla S. (2005-02-28). "In vitro antifungal activity of dragon's blood from Croton urucurana against dermatophytes". Journal of Ethnopharmacology. 97 (2): 409–412. doi:10.1016/j.jep.2004.11.033. ISSN   0378-8741. PMID   15707783.
  17. ↑ Vaisberg, A. J.; Milla, M.; Planas, M. C.; Cordova, J. L.; de Agusti, E. R.; Ferreyra, R.; Mustiga, M. C.; Carlin, L.; Hammond, G. B. (April 1989). "Taspine is the cicatrizant principle in Sangre de Grado extracted from Croton lechleri". Planta Medica. 55 (2): 140–143. doi:10.1055/s-2006-961907. ISSN   0032-0943. PMID   2748730.
  18. 1 2 Ubillas, R.; Jolad, S.D.; Bruening, R.C.; Kernan, M.R.; King, S.R.; Sesin, D.F.; Barrett, M.; Stoddart, C.A.; Flaster, T.; Kuo, J.; Ayala, F. (September 1994). "SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago)". Phytomedicine. 1 (2): 77–106. doi: 10.1016/S0944-7113(11)80026-7 . PMID   23195881.
  19. ↑ Maldonado-Sánchez, Milagros; Aguinaga-Villegas, Dante; Nieto-Gamboa, José; Fonseca-Arellano, Félix; Shardin-Flores, Linda; Cadenillas-Albornoz, Violeta (May 2019). "Estrategias de aprendizaje para el desarrollo de la autonomía de los estudiantes de secundaria". Propósitos y Representaciones. 7 (2): 415–439. doi: 10.20511/pyr2019.v7n2.290 .
  20. ↑ Wyde, Philip R.; Ambrose, Mark W.; Meyerson, Laurence R.; Gilbert, Brian E. (February 1993). "The antiviral activity of SP-303, a natural polyphenolic polymer, against respiratory syncytial and parainfluenza type 3 viruses in cotton rats". Antiviral Research. 20 (2): 145–154. doi:10.1016/0166-3542(93)90004-3. PMID   8384824.
  21. ↑ Barnard, D. L.; Smee, D. F.; Huffman, J. H.; Meyerson, L. R.; Sidwell, R. W. (May 1993). "Antiherpesvirus activity and mode of action of SP-303, a novel plant flavonoid". Chemotherapy. 39 (3): 203–211. doi:10.1159/000239127. ISSN   0009-3157. PMID   7685261.
  22. ↑ LeDuc, James (June 1997). "International Conference on Emerging Infectious Diseases in the Pacific Rim, Bangkok, Thailand". Emerging Infectious Diseases. 3 (2): 248–249. doi: 10.3201/eid0302.970229 .
  23. ↑ "Head Start's 9th National Research Conference Program, June 23-25, 2008, Washington, DC: (584792012-001)". 2008. doi:10.1037/e584792012-001.{{cite journal}}: Cite journal requires |journal= (help)
  24. 1 2 Tradtrantip, Lukmanee; Namkung, Wan; Verkman, A. S. (January 2010). "Crofelemer, an Antisecretory Antidiarrheal Proanthocyanidin Oligomer Extracted from Croton lechleri, Targets Two Distinct Intestinal Chloride Channels". Molecular Pharmacology. 77 (1): 69–78. doi:10.1124/mol.109.061051. ISSN   0026-895X. PMC   2802429 . PMID   19808995.
  25. 1 2 Cai, Y.; Evans, F.J.; Roberts, M.F.; Phillipson, J.D.; Zenk, M.H.; Gleba, Y.Y. (January 1991). "Polyphenolic compounds from Croton lechleri". Phytochemistry. 30 (6): 2033–2040. doi:10.1016/0031-9422(91)85063-6.
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