CRTON LECHLERI Abstrcts J Ethnopharmacol. 2012 Dec 18;144(3):747-53. doi: 10.1016/j.jep.2012.10.032. Epub 2012 Oct 30.

Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against human melanoma SK23 and colon cancer HT29 cell lines. Montopoli M, Bertin R, Chen Z, Bolcato J, Caparrotta L, Froldi G.

Source

Department of Pharmaceutical and Pharmacological Sciences, Padua University, Largo E. Meneghetti 2, Padua, Italy.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Croton lechleri Mull. Arg. (Euphorbiaceae) is a traditional medicinal plant which produces a red sap, traditionally known as "Sangre de Drago"; it is used in folk medicine externally for wounds, fractures, and haemorrhoids, internally for intestinal and stomach ulcers and also for the empirical cure of cancers.

MATERIALS AND METHODS:

We investigated the effects of Croton lechleri sap and taspine in comparison with taxol and vinblastine on the growth of human cancer cell lines of SK23 (melanoma), LoVo and HT29 (colorectal cancer) using MTT and Trypan blue assays. Further, we studied cell cycle by flow cytometry and detected acetylated--tubulin by confocal microscope.

RESULTS:

Croton lechleri inhibited cell proliferation starting from 1 g/mL in SK23 cells, whereas 10 times higher concentrations were required for growth inhibition of HT-29 and LoVo cell lines. Also taspine (0.1 g/mL) inhibited the SK23 and HT29 cell proliferation. Further, assay was assessed on SK23 and HT29 cell lines with 24-48 h treatment with sap and taspine. Both sap and taspine inhibited cancer cell proliferation; taspine showed higher activity on SK23 cells, which was significantly increased after 48 h of SK23 treatment. Using confocal microscopy we observed that Croton lechleri (1 g/mL) caused a loss of microtubule structure, whereas taspine (0.5 g/mL) caused an increase in acetylated -tubulin and a modification of cellular morphology, mainly in SK23 cells. Croton lechleri sap 10 and 50 g/mL influence cell cycle; 50 g/mL sap caused a dramatic reduction of cells in G(1)/G(0) and S phases with a great increase of subG(0) cells.

CONCLUSIONS:

The data showed that Croton lechleri and taspine could inhibit cell proliferation with higher potency against melanoma SK23 cells, supporting the empirical use of the sap as anticancer in ethnomedicine and taspine as a possible anticancer agent.

Planta Med. 1989 Apr;55(2):140-3.

Taspine is the cicatrizant principle in Sangre de Grado extracted from Croton lechleri. Vaisberg AJ, Milla M, Planas MC, Cordova JL, de Agusti ER, Ferreyra R, Mustiga MC, Carlin L, Hammond GB.

Abstract

Sangre de Grado extract used by Peruvian natives as a cicatrizant agent, was collected from trees of the species Croton lechleri growing in the Peruvian jungle. The Sangre de Grado was found to contain one alkaloid identified as taspine and which was shown to be the active cicatrizant principle by an in vivo test in mice. This alkaloid exhibited a dose-related cicatrizant effect and an ED50 of 0.375 mg/kg. Experiments with taspine hydrochloride in order to study its mechanism of action in cell culture systems showed that the alkaloid was non-toxic to human foreskin fibroblasts at concentrations below 150 ng/ml and that it had no effect on cell proliferation. On the other hand, taspine hydrochloride was found to increase the migration of human foreskin fibroblasts. This effect on the migration of fibroblasts is probably the mechanism by which Sangre de Grado and taspine hydrochloride accelerate the wound healing process. Using the two-stage mouse skin carcinogenesis system, we have been able to show that neither Sangre de Grado nor taspine hydrochloride had carcinogenic or tumour promoter activity after 17 months of treatment.

Proc Soc Exp Biol Med. 1993 May;203(1):18-25.

Enhancement of wound healing by the alkaloid taspine defining mechanism of action. Porras-Reyes BH, Lewis WH, Roman J, Simchowitz L, Mustoe TA.

Source

Division of Plastic Surgery, Washington University School of Medicine, Saint Louis, Missouri 63110.

Abstract

Taspine (mol wt 369,000) is an alkaloid extracted from trees of Croton (family Euphorbiaceae) of the western Amazon region that has been used by natives and others as a vulnerary agent. Taspine was purified from tree sap to test its healing properties using different topical concentrations in the paired rat surgical incision model. Wound tensile strength and histology were evaluated. Samples treated with 250 micrograms, but not those treated with 50 micrograms or 10 micrograms, had significant higher values for MBS than paired controls (26%, P < 0.005, and 30%, P < 0.001, by Days 5 and 7, respectively). Taspine did not modify MBS at Day 12. Sample treated with 250 micrograms had significantly greater mononuclear cellular infiltration at Days 5 and 7 but not at Day 12. To better understand the effect of taspine as an enhancer of wound healing, we conducted in vitro studies in cell cultures. Taspine stimulated chemotaxis for fibroblasts. Taspine did not have an effect on specific assays for macrophage chemotaxis, neutrophil activation, fibroblast proliferation, or matrix assembly. Taken together, the data suggest that taspine promotes early phases of wound healing in a dose-dependent manner with no substantial modification thereafter. Its mechanism of action is probably related to its chemotactic properties on fibroblasts and is not mediated by changes in extracellular matrix.

J Altern Complement Med. 2003 Dec;9(6):877-96.

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. Jones K.

Source

Armana Research, Inc., Halfmoon Bay, British Columbia, Canada. armana@dccnet.com

Abstract

OBJECTIVE:

The objective of this review is to provide an overview of the pharmacologic evidence that may or may not support clinical and ethnomedical uses of the sap of sangre de drago (dragon's blood; Croton lechleri Mll.

Arg.). Data sources used were BIOSIS, EMBASE, PubMed, TOXLIT, International Pharmaceutical Abstracts, manual searches, papers on file from peer-reviewed journals, textbooks available at Armana Research, Inc., and researchers in the field of South American botanical medicine.

CONCLUSIONS:

The results of in vitro and in vivo studies largely support the majority of ethnomedical uses of sangre de drago including the treatment of diarrhea, wounds, tumors, stomach ulcers, herpes infection, the itching, pain and swelling of insect bites, and other conditions. Clinical studies of sangre de drago products have reported positive results in the treatment of traveler's and watery diarrhea and the symptoms of insect bites. Because the sap has shown low toxicity and preparations used in clinical studies were well tolerated, further clinical and pharmacologic studies are anticipated. Acknowledgment of the diversity in the chemical makeup of the sap from one geographic area to another and the recent characterization of alkaloid chemotypes of sangre de drago will require that materials developed for clinical use are standardized.

Exp Dermatol. 2010 Sep;19(9):796-9. doi: 10.1111/j.1600-0625.2010.01090.x.

Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation. Pereira U, Garcia-Le Gal C, Le Gal G, Boulais N, Lebonvallet N, Dorange G, Lefeuvre L, Gougerot A, Misery L.

Source

University of Western Brittany, Laboratory of Nervous Factors and Tissular Struturation (EA 4326), Brest, France.

Abstract

Sangre de drago (SD) is a viscous bright red resin collected from Croton lechleri trees that grow in the South American jungle. This sap is used extensively in the native pharmacopoeia to treat skin disorders. Its effectiveness as an inhibitor of neurogenic inflammation has been recently demonstrated. To understand the underlying mechanisms of these effects, we examined the ability of SD to reduce substance P (SP) release in an in vitro model of cutaneous neurogenic inflammation (CNI). This model is based on an enzyme immunoassay of SP (an inducer of CNI) in a porcine co-culture of dorsal root ganglion neurons and keratinocytes. After incubation with different concentrations of SD, we noted an immediate and significant dose-dependent decrease in basal SP release, with average values of 32% at 1% SD (v/v) and 26% at 0.1% (v/v). On the other hand, pretreatment (72 or 1 h) of the co-culture with 1% SD (v/v) was sufficient to induce a 111% (72 h) or 65% (1 h) inhibition of capsaicin-induced SP release, while 0.1% SD (v/v) triggered a 109% (72 h) or 30% (1 h) inhibition. We conclude that sangre de drago is a potent inhibitor of CNI through direct inhibition of neuropeptide release by sensory afferent nerves.

Altern Med Rev. 2001 Dec;6(6):567-79.

Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado. Williams JE.

Source

California Acupuncture College, San Diego, CA, USA. drwilliams665@home.com

Abstract

Viral diseases, including emerging and chronic viruses, are an increasing worldwide health concern. As a consequence, the discovery of new antiviral agents from plants has assumed more urgency than in the past. A number of native Amazonian medicines of plant origin are known to have antimicrobial and anti-inflammatory activity, although only a few have been studied for their antiviral properties and immunomodulating effects. Those most studied include: Sangre de Grado (drago) (Croton lechleri) in the Euphorbiaceae family and Una de Gato (Uncaria tomentosa) in the Rubiaceae family. This article reviews the chemical composition, pharmacological properties, state of current research, clinical use, and potential antiviral and immunomodulating activity of these and other plants from the Peruvian Amazon.

Phytomedicine. 2009 Aug;16(8):768-75. doi: 10.1016/j.phymed.2009.02.003. Epub 2009 Apr 29.

Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles. Froldi G, Zagotto G, Filippini R, Montopoli M, Dorigo P, Caparrotta L.

Source

Department of Pharmacology and Anaesthesiology, University of Padova, Padua, Italy. g.froldi@unipd.it

Abstract

The effects of red sap from Croton lechleri (SdD), Euphorbiaceae, on vascular and gastric smooth muscles were investigated. SdD, from 10 to 1000 microg/ml, induced concentration-dependent vasoconstriction in rat caudal arteries, which was endothelium-independent. In arterial preparations pre-constricted by phenylephrine (0.1 microM) or KCl (30 mM), SdD also produced concentration-dependent vasoconstriction. To study the mechanisms implicated in this effect we used selective inhibitors such as prazosin (0.1 microM), an antagonist of alpha(1)-adrenoceptors, atropine (0.1 microM), an antagonist of muscarinic receptors, and ritanserin (50 nM), a 5-HT(2A) antagonist; none of these influenced vasoconstriction caused by SdD. Likewise, nifedipine (50 nM), an inhibitor of L-type calcium channels, did not modify the action of SdD. Capsaicin (100 nM), an agonist of vanilloid receptors, also did not affect vasoconstriction by SdD. We also investigated the action of SdD (10-1000 microg/ml) on rat gastric fundus; per se the sap slightly increased contractile tension. When the gastric fundus was pre-treated with SdD (100 microg/ml) the contraction induced by carbachol (1 microM) was increased, whereas that by KCl (60mM) or capsaicin (100 nM) were unchanged. The data shows that SdD increased contractile tension in a concentration-dependent way, both on vascular and gastric smooth muscles. The vasoconstriction is unrelated to alpha(1), M, 5-HT(2A) and vanilloid receptors as well as L-type calcium channels. SdD increased also contraction by carbachol on rat gastric fundus. Thus for the first time, experimental data provides evidence that sap from C. lechleri owns constricting activity on smooth muscles.

Molecules. 2008 Jun 1;13(6):1219-29.

Identification of minor secondary metabolites from the latex of Croton lechleri (Muell-Arg) and evaluation of their antioxidant activity. De Marino S, Gala F, Zollo F, Vitalini S, Fico G, Visioli F, Iorizzi M.

Source

Dipartimento di Chimica delle Sostanze Naturali, Universit degli Studi di Napoli Federico II,Via D. Montesano 49, I-80131 Napoli, Ita. sidemari@unina.it

Abstract

Dragon's blood (Sangre de drago), a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae), is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous

extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-beta-O-4'- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods ((1)H-, (13)C- NMR and 2D-NMR experiments), ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex) exhibited the highest antioxidant activity.

Planta Med. 2003 Sep;69(9):785-94.

Immunomodulatory activity and chemical characterisation of sangre de drago (dragon's blood) from Croton lechleri. Risco E, Ghia F, Vila R, Iglesias J, Alvarez E, Caigueral S.

Source

Unitat de Farmacologia i Farmacognsia, Facultat de Farmcia, Universitat de Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain.

Abstract

The immunomodulatory activity of the latex from Croton lechleri (sangre de drago) was determined by in vitro assays. Classical (CP) and alternative (AP) complement pathways activities were determined in human serum. Intracellular generation of reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) and monocytes, and phagocytosis of opsonised fluorescent microspheres were measured by flow cytometry. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Activity on proliferation of murine lymphocytes was also investigated. In addition, anti-inflammatory activity was assayed in vivo by carrageenan-induced rat paw oedema test. Some of the activities were compared with those of the isolated alkaloid taspine. Sangre de drago from Croton lechleri showed immunomodulatory activity. It exhibited a potent inhibitory activity on CP and AP of complement system and inhibited the proliferation of activated T-cells. The latex showed free radical scavenging capacity. Depending on the concentration, it showed antioxidant or prooxidant properties, and stimulated or inhibited the phagocytosis. Moreover, the latex has strong anti-inflammatory activity when administered i. p. Taspine cannot be considered the main responsible for these activities, and other constituents, probably proanthocyanidins, should be also involved.

J Ethnopharmacol. 2004 Dec;95(2-3):437-45.

Mutagenic and antioxidant activities of Croton lechleri sap in biological systems. Lopes MI, Saffi J, Echeverrigaray S, Henriques JA, Salvador M.

Source

Instituto de Biotecnologia da Universidade de Caxias do Sul (UCS), Rua Francisco Getlio Vargas, 1130 Caxias do Sul, RS, Brazil.

Abstract

The sap of Croton lechleri Muell.-Arg (Euphorbiaceae), called Dragon's blood, is used in folk medicine as a cicatrizant, anti-inflammatory and to treat cancer. In this research, the antioxidant activity of Croton lechleri sap was evaluated against the yeast Saccharomyces cerevisiae and against maize plantlets treated with the oxidative agents apomorphine and hydrogen peroxide. The mutagenic activity of the sap was also analyzed using the Salmonella/microsome assay (Salmonella typhimurium TA97a, TA98, TA100, TA102, TA1535) and

in cells of the yeast Saccharomyces cerevisiae. The results showed that Croton lechleri sap possesses significant antioxidant activity against the oxidative damages induced by apomorphine in Saccharomyces cerevisiae under all the conditions studied. However, in the case of hydrogen peroxide, antioxidant activity of the sap was detected only in cells in the stationary phase of growth. The sap was also able to protect cells of the maize plantlets from the toxic effect of apomorphine. This sap showed mutagenic activity for strain TA1535 of Salmonella typhimurium in the presence of metabolic activation and a weak mutagenic activity for strain TA98. These strains detect base pair substitutions and frameshift mutations, respectively. Mutagenicity was also observed in a haploid Saccharomyces cerevisiae strain XV185-14c for the lys1-1, his1-7 locus-specific reversion and hom3-10 frameshift mutations

Planta Med. 1994 Dec;60(6):541-5.

Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon's blood. Chen ZP, Cai Y, Phillipson JD.

Source

Department of Pharmacognosy, School of Pharmacy, University of London, U.K.

Abstract

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 sap has little effect upon the proliferation of endothelial cells, and no single active ingredient was identified. A mechanism for the wound-healing property of the sap has been proposed.

Phytomedicine. 1994 Sep;1(2):77-106. doi: 10.1016/S0944-7113(11)80026-7.

SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago). Ubillas R, Jolad SD, Bruening RC, Kernan MR, King SR, Sesin DF, Barrett M, Stoddart CA, Flaster T, Kuo J, Ayala F, Meza E, Castael M, McMeekin D, Rozhon E, Tempesta MS, Barnard D, Huffman J, Smee D, Sidwell R, Soike K, Brazier A, Safrin S, Orlando R, Kenny PT, Berova N, Nakanishi K.

Source

Shaman Pharmaceuticals, 213 East Grand Avenue, South San Francisco, CA 94080-4812, U.S.A.

Abstract

SP-303, a large proanthocyanidin oligomer isolated from the latex of the plant species Croton lechleri (Eupborbiaceae) 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. 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. Antiviral effects of SP-303 were measured by three distinct methods: CPE, MTT and precursor uptake/incorporation. Cytotoxicity endpoints were markedly greater than the respective antiviral endpoints. SP-303 exhibited activity in RSV-infected cotton rats and African green monkeys, PIV-3-infected cotton rats, HSV-2 infected mice and guinea pigs and FLU-A-infected mice. The most successful routes of SP-303 administration for producing efficacy were: topical application to HSV-2- genital lesions in mice and guinea pigs, aerosol inhalation to FLU-A-infected mice and PIV-3-infected cotton rats, and oral

dosage to RSV-infected cotton rats. A variety of toxicological evaluations demonstrated the safety of SP-303, particularly orally, which was predictable, since condensed tannins are a common dietary component. It is notable that the larger proanthocyanidins as a class have high antiviral activity, whereas most of the monomers are inactive. Clinical trials are ongoing to evaluate SP-303 as a therapeutic antiviral agent