Anticancerous & Cytotoxic Actions:
Alonso-Castro, A., et al. "Rutin exerts antitumor effects on nude mice bearing SW480 tumor." Arch. Med. Res. 2013 Jul; 44(5): 346-51.

Castelli, S., et al. "A natural anticancer agent taspine targets human topoisomerase IB." Anticancer Agents Med. Chem. 2013 Feb; 13(2): 356-63.

Montopoli, M., et al. "Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against human melanoma SK23 and colon cancer HT29 cell lines." J. Ethnopharmacol. 2012 Dec 18; 144(3): 747-53.

Zhang, Y., et al. "Antitumor activity of taspine by modulating the EGFR signaling pathway of Erk1/2 and Akt in vitro and in vivo." Planta Med. 2011 Nov;77(16):1774-81.

Alonso-Castro, A., et al. "Antitumor effect of Croton lechleri Mull. Arg. (Euphorbiaceae). J Ethnopharmacol. 2012 Mar; 140(2): 438-42.

Lu, W., et al. "A novel taspine analog, HMQ1611, inhibits growth of non-small cell lung cancer by inhibiting angiogenesis." Oncol. Lett. 2012 Nov; 4(5): 1109-1113.

Zhang, Y., et al. "A novel angiogenesis inhibitor impairs LoVo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation." Cell Death Dis. 2012 Oct 11; 3: e406. (LoVo cells are human colon cancer cells)

He, H., et al. "Tas13D inhibits growth of SMMC-7721 cell via suppression VEGF and EGF expression." Asian Pac. J. Cancer Prev. 2012; 13(5): 2009-14.

Zhang, Y., et al. "Facile synthesis and biological evaluation of novel symmetrical biphenyls as antitumor agents." Med Chem. 2012 Mar; 8(2): 145-50.

Zhang, Y., et al. "Effects of taspine on proliferation and apoptosis by regulating caspase-3 expression and the ratio of Bax/Bcl-2 in A431 cells." Phytother Res. 2011 Mar; 25(3): 357-64. (A431 cells are squamous cell skin cancer)

Zhan, Y., et al. "Activity of taspine isolated from Radix et Rhizoma Leonticis against estrogen-receptor-positive breast cancer." Fitoterapia. 2011 Sep; 82(6): 896-902.
Takami, Y., et al. "Proanthocyanidin derived from the leaves of Vaccinium virgatum suppresses platelet-derived growth factor-induced proliferation of the human hepatic stellate cell line LI90." Hepatol Res. 2010 Apr; 40(4): 337-45.

Fayed, W., et al. "Identification of a novel topoisomerase inhibitor effective in cells overexpressing drug efflux transporters." PLoS One. 2009 Oct; 4(10): e7238.

Zhang, Y., et al. "[Inhibitory effect of taspine on mouse S180 sarcoma and its mechanism]." Zhongguo Zhong Yao Za Zhi. 2007 May; 32(10) :953-6.

Gonzales, G., et al. "Medicinal plants from Peru: a review of plants as potential agents against cancer." Anticancer Agents Med, Chem. 2006 Sep; 6(5) :429-44.

Rossi, D., et al. "Evaluation of the mutagenic, antimutagenic and antiproliferative potential of Croton lechleri (Muell. Arg.) latex." Phytomedicine. 2003 Mar; 10(2-3): 139-44.

Sandoval, M., et al. "Sangre de grado (Croton palanostigma) induces apoptosis in human gastrointestinal cancer cells." J. Ethnopharmacol. 2002; 80(2-3): 121-9.

Chen, Z., et al. "Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon’s blood." Planta Med. 1994; 60(6): 541-45.

Pieters, L., et al. "Isolation of a dihydrobenzofuran lignan from South American dragon’s blood (Croton sp.) as an inhibitor of cell proliferation." J. Nat. Prod. 1993; 56(6): 899-906.

Itokawa, H., et al. "A cytotoxic substance from sangre de grado." Chem. Pharm. Bull. 1991; 39(4): 1041-42.

Wound Healing, Neuromuscular, & Cellular Protective Antioxidant Actions:
Pona, A., et al. "Review of future insights of Dragon's Blood in dermatology." Dermatol. Ther. 2018 Nov 22: e12786.

Escobar, J., et al. "Dragon's blood sap: storage stability and antioxidant activity." Molecules. 2018 Oct 15; 23(10).

Bogdan, C., et al. "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; 11: 521-531.

Martins, C., et al. "Dragon's blood sap (Croton lechleri) as storage medium for avulsed teeth: in vitro study of cell viability." Braz. Dent. J. 2016 Oct-Dec; 27(6): 751-756.

Namjoyan, F., et al. "Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial." J. Tradit. Complement. Med. 2015 Jan; 6(1): 37-40.

Rossi, D., et al. "Croton lechleri Müll. Arg. (Euphorbiaceae) stem bark essential oil as possible mutagen-protective food ingredient against heterocyclic amines from cooked food." Food Chem. 2013 Aug; 139(1-4): 439-47.

Pereira, U., et al. "Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation." Exp. Dermatol. 2010 Sep; 19(9): 796-9.

De Marino, S., et al. "Identification of minor secondary metabolites from the latex of Croton lechleri (Muell-Arg) and evaluation of their antioxidant activity." Molecules. 2008 Jun; 13(6): 1219-29.

Frum, Y., et al. "In vitro 5-lipoxygenase and anti-oxidant activities of South African medicinal plants commonly used topically for skin diseases." Skin Pharmacol. Physiol. 2006; 19(6): 329-35.

Rollinger, J., "Taspine: bioactivity-guided isolation and molecular ligand-target insight of a potent acetylcholinesterase inhibitor from Magnolia x soulangiana." J. Nat. Prod. 2006 Sep; 69(9): 1341-6.

Dong, Y., et al. "Enhancement of wound healing by taspine and its effect on fibroblast." Zhong. Yao. Cai. 2005; 28(7): 579-82.

Dong, Y., et al. "Effect of taspine hydrochloride on skin wound healing in rats and its mechanism." Zhong. Xi. Yi. Jie. He. Xue. Bao. 2005 Sep; 3(5): 386-90.

Lopes, M., et al. "Mutagenic and antioxidant activities of Croton lechleri sap in biological systems." J. Ethnopharmacol. 2004 Dec; 95(2-3): 437-45.

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 Dec; 9(6): 877-96.

Desmarchelier, C., et al. "Effects of sangre de drago from Croton lechleri Muell.-Arg. on the production of active oxygen radicals." J. Ethnopharmacol. 1997; 58: 103-8.

Phillipson, J. "A matter of some sensitivity." Phytochemistry. 1995 Apr; 38(6): 1319-43.
Chen, Z., et al. "Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon’s blood." Planta Med. 1994; 60(6): 541-45.

Porras-Reyes, B., et al. "Enhancement of wound healing by the alkaloid taspine defining mechanism of action." Proc. Soc. Exp. Biol. Med. 1993; 203(1): 18-25.

Vaisberg, A., et al. "Taspine is the cicatrizant principle in sangre de grado extracted from Croton lechleri." Planta Med. 1989; 55(2): 140-43.

Macrae, W., et al. "Studies on the pharmacological activity of Amazonian Euphorbiaceae." J. Ethnopharmacol. 1988; 22(2): 143-72.

Pain-relieving & Anti-inflammatory Actions:
Gordon, W., et al. "A nonsteroidal novel formulation targeting inflammatory and pruritus-related mediators modulates experimental allergic contact dermatitis." Dermatol. Ther. 2018 Mar; 8(1): 111-126.

Pereira, U., et al. "Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation." Exp Dermatol. 2010 Sep; 19(9): 796-9.

Xiangming, L., et al. "Effects of dragon's blood resin and its component loureirin B on tetrodotoxin-sensitive voltage-gated sodium currents in rat dorsal root ganglion neurons." Sci. China C. Life Sci. 2004 Aug; 47(4): 340-8.

Tsacheva, I., et al. "Complement inhibiting properties of dragon's blood from Croton draco. "Z. Naturforsch. 2004; 59(7-8): 528-32.

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 Dec; 9(6): 877-96.

Risco, E., et al. "Immunomodulatory activity and chemical characterisation of sangre de drago (dragon's blood) from Croton lechleri." Planta Med. 2003; 69(9): 785-94.

Miller, M., et al. "Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado." J. Invest. Dermatol. 2001; 117(3): 725-30.

Perdue, G., et al. "South American plants II: Taspine isolation and anti-inflammatory activity." J. Pharm. Sci. 1979; 68(1): 124-26.

Antimicrobial & Antiviral Actions:
Extracts of sangre de grado have demonstrated antiviral activity against influenza, parainfluenza, Herpes simplex viruses I and II, and Hepatitis A and B. The antiviral and anti-diarrheal properties of sangre de grado came to the the attention of the pharmaceutical industry in the mid 1990's.. A U.S.-based pharmaceutical company filed patents on three pharmaceutical preparations that contain antiviral constituents and novel chemicals (a group of plant flavonoids they named SP-303), extracted from the bark and resin of sangre de grado. Their patented drugs include an oral product for the treatment of respiratory viral infections, a topical antiviral product for the treatment of herpes, and an oral product for the treatment of persistent diarrhea.

Roumy, V., et al. "In vitro antimicrobial activity of traditional plant used in mestizo shamanism from the Peruvian Amazon in case of infectious diseases." Pharmacogn. Mag. 2015 Oct; 11(Suppl 4): S625-33.

Rodriguez-Garcia, A., et al. "Development and in vitro evaluation of biopolymers as a delivery system against periodontopathogen microorganisms." Acta Odontol. Latinoam. 2010; 23(2): 158-63.

Gurgel, L., et al. "In vitro antifungal activity of dragon's blood from Croton urucurana against dermatophytes." J. Ethnopharmacol. 2005; 97(2): 409-12.

Williams, J. "Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado." Altern. Med. Rev. 2001; 6(6): 567-79.

Ubillas, R., et al. "SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago)." Phytomedicine. 1994 Sep; 1(2): 77-106.

Sidwell R., et al. "Influenza virus-inhibitory effects of intraperitoneally and aerosol-administered SP-303, a plant flavonoid." Chemotherapy. 1994; 40(1): 42-50.
Chen, Z., et al. "Studies on the anti-tumour, an
ti-bacterial, and wound-healing properties of dragon’s blood." Planta Med. 1994; 60(6): 541-45.

Rao, G., et al. "Antimicrobial agents from higher plants. Dragon's blood resin."J. Nat. Prod. 1982 Sep-Oct; 45(5): 646-8.

Anti-ulcer & Anti-diarrhea Actions:
Teixeira, A., et al. "Prophylactic use of a standardized botanical extract for the prevention of naturally occurring diarrhea in newborn Holstein calves." J. Dairy Sci. 2017 Apr; 100(4): 3019-3030.

Gao, J., et al. "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.

Lock, O., et al. "Bioactive compounds from plants used in Peruvian traditional medicine." Nat. Prod. Commun. 2016 Mar; 11(3): 315-37.

Teixeira, A., et al. "Effect of crofelemer extract on severity and consistency of experimentally induced enterotoxigenic Escherichia coli diarrhea in newborn Holstein calves. J. Dairy Sci. 2015 Nov; 98(11): 8035-43.

Frampton, J., et al. "Crofelemer: a review of its use in the management of non-infectious diarrhoea in adult patients with HIV/AIDS on antiretroviral therapy." Drugs. 2013 Jul; 73(10): 1121-9.

Chordia, P., et al. "Crofelemer, a novel agent for treatment of non-infectious diarrhea in HIV-infected persons." Expert Rev. Gastroenterol. Hepatol. 2013 Sep; 7(7): 591-600.

Cottreau, J., et al. "Crofelemer for the treatment of secretory diarrhea." Expert Rev. Gastroenterol. Hepatol. 2012 Feb; 6(1): 17-23.

Tradtrantip, L., et al. "Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels." Mol. Pharmacol. 2010 Jan; 77(1): 69-78.

Tran, C., et al. "The role of Amazonian herbal medicine Sangre de Grado in Helicobacter pylori infection and its association with metallothionein expression." Helicobacter. 2006 Apr; 11(2): 134-5.

Paula, A., et al. "The gastroprotective effect of the essential oil of Croton cajucara is different in normal rats than in malnourished rats." Br. J. Nutr. 2006 Aug; 96(2): 310-5.

Fischer, H., 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.

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 Dec; 9(6): 877-96.

Miller, M., et al. "Treatment of gastric ulcers and diarrhea with the Amazonian herbal medicine sangre de grado." Am. J. Physiol. Gastrointest. Liver Physiol. 2000; 42: G192-200.

Gabriel, S., et al. "A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion." Am. J. Physiol. 1999 Jan; 276(1 Pt 1): G58-63.

Holodniy, 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 Nov; 94(11): 3267-73.

Vasoconstrictive Action:
Froldi, G., et al. "Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles." Phytomedicine. 2009 Aug; 16(8): 768-75.

Taspine and Derivatives Research:
The main active plant chemical in sangre de grado resin is a phenolic lignan called taspine. The first drug product derived from sangre de grado was naturally extracted taspine and called SP-303 in the mid 1990's. It was trialed for HIV/Aids related diarrhea due to the resin’s antiviral actions as well as its traditional uses and efficacy in treating diarrhea. This chemical has been synthesized now (no sangre de grado resin is used) and turned into a prescription drug in the U.S. called crofelemer (generic name) and Mytesi and Fulyzaq (brand names). These drug products were FDA-approved in 2012 to treat HIV/AIDS related diarrhea, much like the natural resin does, which is how these pharmaceutical companies discovered taspine in sangre de grado in the first place. Other research groups in China are extracting this same taspine alkaloid from a different plant that grows in China called Radix et Rhizoma Leonticis. They are actively engaged in creating new novel chemicals derived from the taspine natural chemical called "derivatives" (changing the taspine molecule just enough to be patentable without losing any of the anti-cancerous benefits of the actual taspine chemical) in the search of other patentable cancer drugs.

Here is that research:
Yang, T., et al. "Novel compounds TAD-1822-7-F2 and F5 inhibited HeLa cells growth through the JAK/Stat signaling pathway. Biomed. Pharmacother. 2018 Jul; 103: 118-126.

Ma, W., et al. "Synergistic effect of TPD7 and berberine against leukemia Jurkat cell growth through regulating Ephrin-B2 signaling." Phytother. Res. 2017 Sep; 31(9): 1392-1399.

Dai, B., et al. "Taspine derivative 12k suppressed A549 cell migration through the Wnt/β-catenin and EphrinB2 signaling pathway. Biomed. Pharmacother. 2017 Mar; 87: 102-109.
Dai, B., et al. "A taspine derivative supresses Caco-2 cell growth by competitively targeting EphrinB2 and regulating its pathway. Oncol. Rep. 2016 Sep; 36(3): 1526-34.

Liu, R., et al. "Taspine derivative TAS9 regulates cell growth and metastasis of human hepatocellular carcinoma." Mol. Med. Rep. 2015 Nov; 12(5): 7735-41.

Zhang, D., et al. "c-Myc plays a key role in TADs-induced apoptosis and cell cycle arrest in human hepatocellular carcinoma cells." Am. J. Cancer Res. 2015 Feb; 5(3): 1076-88.
Dai, B., et al. "Novel taspine derivative 12k inhibits cell growth and induces apoptosis in lung cell carcinoma." Biomed. Pharmacother. 2015 Mar; 70: 227-33.

Zhan, Y., et al. "A novel taspine derivative, HMQ1611, suppresses adhesion, migration and invasion of ZR-75-30 human breast cancer cells." Breast Cancer. 2014 May; 21(3): 334-40.

Wang, N., et al. "A novel taspine derivative suppresses human liver tumor growth and invasion in vitro and in vivo." Oncol. Lett. 2013 Sep; 6(3): 855-859.

Du, H.,et al. "Rapid characterization of a novel taspine derivative-HMQ1611 binding to EGFR by a cell membrane chromatography method." Comb. Chem. High Throughput Screen. 2013 May; 16(4): 324-9.

Lu, W., et al. "A novel taspine analog, HMQ1611, inhibits growth of non-small cell lung cancer by inhibiting angiogenesis." Oncol. Lett. 2012 Nov; 4(5): 1109-1113.

Zhang, Y., et al. "A novel angiogenesis inhibitor impairs lovo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation." Cell Death Dis. 2012 Oct 11; 3: e406.

He, H. Et al. "Tas13D inhibits growth of SMMC-7721 cell via suppression VEGF and EGF expression. Asian Pac. J. Cancer Prev. 2012; 13(5): 2009-14.

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