Pharmacological potential of Euphorbia tirucalliL. latex in gastric adenocarcinoma: from an ethnopharmacological perspective into new products.

Products derived from the latex of Euphorbia tirucalli were obtained through hydrolysis and column chromatography, resulting in products rich in triterpenes, ingenol 3-esters (I3E), and other derivatives from hydrolysed latex. These products underwent evaluation for their cytotoxic activity against gastric adenocarcinoma cells (AGS). Triterpene derivatives were synthesised, and the selectivity of each product was assessed. The results were compared with the previously described crude latex. Triterpenes and I3E were analysed in silico for their affinity with the active site of PKCδC1b. The hydrolysed latex (free of I3E) exhibited high cytotoxicity, albeit with reduced selectivity. Triterpenes and acetylated triterpenes were more cytotoxic than I3E, although the latter showed greater selectivity. Euphol benzoates and cinnamates showed no cytotoxicity. I3E demonstrated high affinity for the PKCδC1b. In summary, triterpenes exhibited higher cytotoxicity against AGS cells, while I3E displayed greater selectivity. Hydrolysed latex shows promise as a potential candidate for future gastric cancer treatment.

Consumption of latex from Euphorbia tirucalli L. promotes a reduction of tumor growth and cachexia, and immunomodulation in Walker 256 tumor-bearing rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia tirucalli L. is an African plant that grows well in Brazil. Individuals diagnosed with cancer frequently consume latex from E. tirucalli, dissolved in drinking water. In vitro studies confirm the antitumor potential of E. tirucalli latex, but in vivo evaluations are scarce. AIM OF THE STUDY: To evaluate the effect of intake of an aqueous solution of E. tirucalli latex on tumor growth, cachexia, and immune response in Walker 256 tumor-bearing rats. MATERIALS AND METHODS: Latex from E. tirucalli was collected and analyzed by LC-MS. Sixty male Wistar rats (age, 90 days) were randomly divided into four groups: C, control group (without tumor); W, Walker 256 tumor-bearing group; SW1, W animals but treated with 25 µL latex/mL water; and SW2, W animals but treated with 50 µL latex/mL water. Animals received 1 mL of latex solution once a day by gavage. After 15 d, animals were euthanized, tumor mass was determined, and glucose and triacylglycerol serum levels were measured by using commercial kits. Change in the body weight during tumor development was calculated, and proliferation capacity of tumor cells was assessed by the Alamar Blue assay. Phagocytosis and superoxide anion production by peritoneal macrophages and circulating neutrophils were analyzed by enzymatic and colorimetric assays. Data are analyzed by one-way ANOVA followed by Tukey's post-hoc test, with the significance level set at 5%. RESULTS: The analysis of the latex revealed the presence of triterpenes. The ingestion of the latex aqueous solution promoted 40% and 60% reduction of the tumor mass in SW1 and SW2 groups, respectively (p < 0.05). The proliferative capacity of tumor cells from SW2 group was 76% lower than that of cells from W group (p < 0.0001). Animals treated with latex gained, on average, 20 g (SW1) and 8 g (SW2) weight. Glucose and triacylglycerol serum levels in SW1 and SW2 animals were similar to those in C group rats. Peritoneal macrophages and blood neutrophils from SW1 and SW2 animals produced 30-40% less superoxide anions than those from W group animals (p < 0.05), but neutrophils from SW2 group showed an increased phagocytic capacity (20%, vs. W group). CONCLUSIONS: E. tirucalli latex, administered orally for 15 d, efficiently reduced tumor growth and cachexia in Walker 256 tumor-bearing rats. Decreased tumor cell proliferative capacity was one of the mechanisms involved in this effect. Further, the data suggest immunomodulatory properties of E. tirucalli latex. The results agree with folk data on the antitumor effect of latex ingestion, indicating that it may be useful as an adjunct in the treatment of cancer patients. For this, further in vivo studies in animal and human models need to be conducted.

Semi-Synthetic Ingenol Derivative from Euphorbia tirucalli Inhibits Protein Kinase C Isotypes and Promotes Autophagy and S-phase Arrest on Glioma Cell Lines.

The identification of signaling pathways that are involved in gliomagenesis is crucial for targeted therapy design. In this study we assessed the biological and therapeutic effect of ingenol-3-dodecanoate (IngC) on glioma. IngC exhibited dose-time-dependent cytotoxic effects on large panel of glioma cell lines (adult, pediatric cancer cells, and primary cultures), as well as, effectively reduced colonies formation. Nevertheless, it was not been able to attenuate cell migration, invasion, and promote apoptotic effects when administered alone. IngC exposure promoted S-phase arrest associated with p21CIP/WAF1 overexpression and regulated a broad range of signaling effectors related to survival and cell cycle regulation. Moreover, IngC led glioma cells to autophagy by LC3B-II accumulation and exhibited increased cytotoxic sensitivity when combined to a specific autophagic inhibitor, bafilomycin A1. In comparison with temozolomide, IngC showed a mean increase of 106-fold in efficacy, with no synergistic effect when they were both combined. When compared with a known compound of the same class, namely ingenol-3-angelate (I3A, Picato®), IngC showed a mean 9.46-fold higher efficacy. Furthermore, IngC acted as a potent inhibitor of protein kinase C (PKC) activity, an emerging therapeutic target in glioma cells, showing differential actions against various PKC isotypes. These findings identify IngC as a promising lead compound for the development of new cancer therapy and they may guide the search for additional PKC inhibitors.

Inhibitory effects of Euphorbia tirucalli latex on murine B16/F10 melanoma cells and lung metastasis.

Euphorbia tirucalli (E. tirucalli) is a tropical and subtropical plant that produces a latex which is used for several purposes. The components of E. tirucalli latex include triterpenes, diterpenes and steroids. The aim of the present study was to evaluate the effects of diluted E. tirucalli latex on murine B16/F10 melanoma cells and lung metastasis. For this purpose, an in vitro study was first performed, in which B16/F10 cells were treated with diluted (1/2 to 1/11,192) E. tirucalli latex. In a second study, B16/F10 melanoma cells were inoculated into the tail vein of mice to generate lung metastases; the mice then received 0.467 µg of latex diluted in 200 ml saline by gavage for 14 days. A significant decrease in B16/F10 cell viability was observed using the MTT assay at 24 and 48 h after treatment with E. tirucalli latex. In addition, a significant decrease in the volume fraction occupied by B16/F10 metastatic colonies in the lungs was observed in mice treated with E. tirucalli latex. These results confirm the antineoplastic effects of diluted E. tirucalli latex.

Analytical methods to access the chemical composition of an Euphorbia tirucalli anticancer latex from traditional Brazilian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia tirucalli L. is widely used by Brazilian folk medicine, mainly for its anticancer activity. However, its commercialization was banned by The Brazilian National Sanitary Surveillance Agency (ANVISA) due to the presence of some compounds considered toxic, such as the diterpene esters. AIM OF THE STUDY: Chemical and biological analyses were performed with the Brazilian Euphorbia tirucalli latex to support its wide traditional use in Brazil. MATERIAL AND METHODS: Latex was collected by using two procedures, in a solution of dichloromethane: methanol (3:1, 100 mL) and in 100 mL of distilled water. The first procedure was concentrated as a crude extract and the second one was partitioned with hexane and dichloromethane. The partitions and crude extract were subjected to phytochemical analyses using three different methods: Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) with electrospray ionization sources in negative mode (ESI(-)) as well as in tandem mass spectrometry ESI(-) MS/MS and Atmospheric Pressure Chemical Ionization in positive mode (APCI(+)), Gas Chromatography coupled Mass Spectrometry (GC-MS) and Nuclear Magnetic Resonance (NMR) (1H-NMR and 13C-NMR). The cytotoxic potential was evaluated using the crude extract in macrophages RAW 264.7 and Gastric Adenocarcinoma (AGS) cancer cells. The evaluation of immunomodulatory activity was made through the detection of Nitric Oxide (NO) and cytokines as Tumor necrosis factor α (TNF-α) and Interleukin-6 (IL-6). RESULTS: GC-MS showed the presence of some esters of fatty acids, for instance myristic, palmitic, stearic, oleic and linoleic acid and, mainly, triterpenes such as euphol and tirucallol. With NMR, most of the signals were related to triterpenoids euphol and tirucallol. However, when the latex was analyzed with ESI(-) FT-ICR MS, a wide variety of molecules from different classes of natural products (fatty acids, diterpenes, triterpenes, steroids) were found. On the other hand, when APCI(+)FT-ICR MS was used, the ion M+. At ratio mass-charge (m/z) 426.38567, related to triterpenes euphol and tirucallol masses, presented the most intense peak, with a mass error of -0.11, indicating high accuracy. Diterpene esters from 4-deoxyphorbol and ingenol were identified only by ESI(-)FT-ICR MS and ESI(-)FT-ICR MS/MS. When evaluated biologically, the crude latex showed immunomodulatory activity, as it reduced the production of the pro-inflammatory cytokines TNF-α, IL-6 and NO, and the effect on NO reduction was more significant, obtaining in a similar result to the N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME) standards, as well as significant cytotoxic activity with half inhibitory concentration (IC50) values of 69.43 ±â€¯1.29 µg/mL against AGS without damaging healthy ones. CONCLUSION: It was verified that the Brazilian Euphorbia tirucalli latex consists mainly of the triterpenes euphol and tirucallol, which may be the main cause of the anticancer activity attributed to the plant, but many other minor compounds could have been determined by the FT-ICR MS method, such as the diterpene esters. It has antitumor potential because it acts selectively against cancer cells and it also prevents the progression of tumors, because it carries an important immunomodulatory effect.

Modified ingenol semi-synthetic derivatives from Euphorbia tirucalli induce cytotoxicity on a large panel of human cancer cell lines.

The latex from Euphorbia tirucalli is used in Brazil as a folk medicine for several diseases, including cancer. Recently, we showed a cytotoxic activity of E. tirucalli euphol in a wide range of cancer cell lines. Moreover, we showed that euphol inhibits proliferation, motility and colony formation in pancreatic cancer cells, induces autophagy and sensitizes glioblastoma cells to temozolomide cytotoxicity. Herein, we report in vitro activity of three semi-synthetic ingenol compounds derived from E. tirucalli, IngA (ingenol-3-trans-cinnamate), IngB (ingenol-3-hexanoate) and IngC (ingenol-3-dodecanoate), against a large panel of human cancer cell lines. Antineoplastic effects of the three semi-synthetic compounds were assessed using MTS assays on 70 cancer cell lines from a wide array of solid tumors. Additionally, their antitumor potential was compared with known compounds of the same class, namely ingenol-3-angelate (Picato®) and ingenol 3,20-dibenzoate and in combination with standard chemotherapeutic agents. We observed that IngA, B, and C exhibited dose-dependent cytotoxic effects. Amongst the semi-synthetic compounds, IngC displayed the best activity across the tumor cell lines. In comparison with ingenol-3-angelate and ingenol 3,20-dibenzoate, IngC showed a mean of 6.6 and 3.6-fold higher efficacy, respectively, against esophageal cancer cell lines. Besides, IngC sensitized esophageal cancer cells to paclitaxel treatment. In conclusion, the semi-synthetic ingenol compounds, in particular, IngC, demonstrated a potent antitumor activity on all cancer cell lines evaluated. Although the underlying mechanisms of action of IngC are not elucidated, our results provide insights for further studies suggesting IngC as a putative therapy for cancer treatment.

In vitro screening of cytotoxic activity of euphol from Euphorbia tirucalli on a large panel of human cancer-derived cell lines.

A large number of classic antineoplastic agents are derived from plants. Euphorbia tirucalli L. (Euphorbiaceae) is a subtropical and tropical plant, used in Brazilian folk medicine against many diseases, including cancer, yet little is known about its true anticancer properties. The present study evaluated the antitumor effect of the tetracyclic triterpene alcohol, euphol, the main constituent of E. tirucalli in a panel of 73 human cancer lines from 15 tumor types. The biological effect of euphol in pancreatic cells was also assessed. The combination index was further used to explore euphol interactions with standard drugs. Euphol showed a cytotoxicity effect against several cancer cell lines (IC50 range, 1.41-38.89 µM), particularly in esophageal squamous cell (11.08 µM) and pancreatic carcinoma cells (6.84 µM), followed by prostate, melanoma, and colon cancer. Cytotoxicity effects were seen in all cancer cell lines, with more than half deemed highly sensitive. Euphol inhibited proliferation, motility and colony formation in pancreatic cancer cells. Importantly, euphol exhibited synergistic interactions with gemcitabine and paclitaxel in pancreatic and esophageal cell lines, respectively. To the best of our knowledge, this study constitutes the largest in vitro screening of euphol efficacy on cancer cell lines and revealed its in vitro anti-cancer properties, particularly in pancreatic and esophageal cell lines, suggesting that euphol, either as a single agent or in combination with conventional chemotherapy, is a potential anti-cancer drug.

Eutirucallin: A Lectin with Antitumor and Antimicrobial Properties.

Eutirucallin is a lectin isolated from the latex of Euphorbia tirucalli, a plant known for its medical properties. The present study explores various characteristics of Eutirucallin including stability, cytotoxicity against tumor cells, antimicrobial and antiparasitic activities. Eutirucallin was stable from 2 to 40 days at 4°C, maintained hemagglutinating activity within a restricted range, and showed optimal activity at pH 7.0-8.0. Eutirucallin presented antiproliferative activity for HeLa, PC3, MDA-MB-231, and MCF-7 tumor cells but was not cytotoxic for non-tumorigenic cells such as macrophages and fibroblasts. Eutirucallin inhibited the Ehrlich ascites carcinoma in vivo and it was also observed that Eutirucallin inhibited 62.5% of Escherichia coli growth. Also, Eutirucallin showed to be effective when tested directly against Toxoplasma gondii infection in vitro. Therefore, this study sheds perspectives for pharmacological applications of Eutirucallin.

Medicinal plants in Brazil: Pharmacological studies, drug discovery, challenges and perspectives.

This review article focuses on pre-clinical and clinical studies with some selected Brazilian medicinal plants in different areas of interest, conducted by research groups in Brazil and abroad. It also highlights the Brazilian market of herbal products and the efforts of Brazilian scientists to develop new phytomedicines. This review is divided into three sections. The section I describes the Brazilian large biodiversity and some attempts of Brazilian scientists to assess the pharmacological profile of most plant extracts or isolated active principles. Of note, Brazilian scientists have made a great effort to study the Brazilian biodiversity, especially among the higher plants. In fact, more than 10,000 papers were published on plants in international scientific journals between 2011 and 2013. This first part also discussed the main efforts to develop new medicines from plants, highlighting the Brazilian phytomedicines market. Despite the large Brazilian biodiversity, notably with the higher plants, which comprise over 45,000 species (20-22% of the total worldwide), and the substantial number of scientific publications on medicinal plants, only one phytomedicine is found in the top 20 market products. Indeed, this market is still only worth about 261 million American dollars. This represents less than 5% of the global Brazilian medicine market. The section II of this review focus on the use of Brazilian plant extract and/or active principles for some selected diseases, namely: central nervous systems disorders, pain, immune response and inflammation, respiratory diseases, gastrointestinal tract and metabolic diseases. Finally, section III discusses in more details some selected Brazilian medicinal plants including: Cordia verbenacea, Euphorbia tirucalli, Mandevilla velutina, Phyllanthus spp., Euterpe oleracea, Vitis labrusca, Hypericum caprifoliatum and Hypericum polyanthemum, Maytenus ilicifolia, Protium kleinii and Protium heptaphylium and Trichilia catigua. Most of these publications are preliminary and only report the effects of crude extracts, both in vitro and in vivo studies. Only very few studies have been dedicated to investigate the mechanisms of action of isolated compounds. Likewise, studies on safety (toxicology), pharmacokinetic, and especially on well-conducted clinical trials are rare. In conclusion, in spite of the abundant Brazilian biodiversity and the thousands of academic publications on plants in international peer-reviewed scientific journals, few patents and medicines have been derived from such studies. Undoubtedly, great efforts must be made to improve the development of plant-derived medicine market in Brazil, especially by involving the partnership between academia and pharmaceutical companies.

EFFECTS OF TOPICAL TREATMENT WITH EUPHORBIA TIRUCALLI LATEX ON THE SURVIVAL AND INTESTINAL ADHESIONS IN RATS WITH EXPERIMENTAL PERITONITIS / EFEITOS DO TRATAMENTO TÓPICO COM O LÁTEX DA EUPHORBIA TIRUCALLI NA SOBREVIDA E NAS ADERÊNCIAS INTESTINAIS DE RATOS COM PERITONITE EXPERIMENTAL

Background: The use of plants of the family Euphorbiaceae, particularly Euphorbia tirucalli (avelós) has been popularly widespread for treating a variety of diseases of infectious, tumoral, and inflammatory. Aim: To demonstrated antimicrobial and immunomodulatory effects of these extracts, evaluating the effect of a topical treatment with an aqueous solution of avelós latex on the survival and on intestinal adhesions in rats with experimental peritonitis. Methods: Peritonitis was induced in 24 Wistar rats, that were randomized into four groups of six as follows: (1) Control group (n=6), no treatment; (2) Antibiotic group (n=6), treatment with a single intramuscular dose of antibiotic Unasyn; (3) Saline group (n=6), the abdominal cavity was washed with 0.9% saline; and (4) E.tirucalli group (n=6), the abdominal cavity was washed with E. tirucalli at a concentration of 12 mg/ml. The animals that died were necropsied, and the time of death was recorded. The survivors were killed on postoperative day 11, and necropsy was subsequently performed for evaluation of the intestinal adhesions. Results: Significant differences were observed in the control and antibiotic groups (p<0.01) with respect to the survival hours when compared with the saline and E. tirucalli groups. There was no significant difference (p>0.05) in the survival of animals in the saline andE. tirucalli groups; however, one animal died in the saline group. Necropsy of the animals in the saline and E. tirucalligroups showed strong adhesions resistant to manipulation, between the intestinal loops and abdominal wall. The remaining groups did not show any adhesions. Conclusions: Topical treatment with E. tirucalli latex stimulated an increased formation of intestinal adhesions and prevented the death of all animals with peritonitis.

Racional: O uso de plantas da família Euphorbiaceae, principalmente a Euphorbia tirucalli (avelós), tem sido popularmente difundido para o tratamento de uma variedade de doenças de natureza infecciosa, tumoral e inflamatória. Objetivo: Avaliar o efeito do tratamento tópico com a solução aquosa do látex do avelós na sobrevida e nas aderências intestinas de ratos com peritonite experimental. Métodos: Foi induzido peritonite em 24 ratos Wistar e randomizados em quatro grupos de seis, assim distribuídos: 1) Controle - (n=6), nenhum tratamento; 2) Antibiótico - (n=6), tratamento com dose única intramuscular de antibiótico Unasyn (Pfizer - São Paulo); 3) Salina - (n=6), lavagem da cavidade abdominal com solução fisiológica 0,9%; 4) E.Tirucalli - (n=6), lavagem da cavidade abdominal com E. tirucalli na concentração de 12 mg/ml. Os animais que morreram foram submetidos à necropsia e o horário do óbito anotado. Os sobreviventes foram submetidos à eutanásia no 11odia de pós-operatório e, posteriormente, realizou-se a necropsia para avaliação da formação de aderências. Resultados: Os grupos controle e antibiótico obtiveram diferença significativa (p<0,01) com relação às horas de vida entre os grupos salina e E. tirucalli. Não houve diferença significativa (p>0,05) na sobrevida dos animais dos grupos salina e E. tirucalli, no entanto, houve um óbito no grupo salina. A necropsia dos animais dos grupos salina e E. tirucalli mostrou aderências firmes e resistentes à manipulação entre alças intestinais e parede abdominal. Os demais grupos não tiveram formação de aderências. Conclusão: O tratamento tópico com o látex da E. tirucalli estimulou maior formação de aderências intestinais e evitou o óbito de todos animais com peritonite até o período avaliado.

Angiogenic activity of latex from Euphorbia tirucalliLinnaeus 1753 (Plantae, Euphorbiaceae) / Atividade angiogênica do látex da Euphorbia tirucalliLinnaeus 1753 (Plantae, Euphorbiaceae)

To assess the pro-angiogenic activity of Euphorbia tirucalli, commonly known as “avelós” plant, we performed a series of tests by applying an aqueous E. tirucalli latex solution (10 mg/mL) to the chorioallantoic membranes (CAMs) of 80 fertilized chicken eggs incubated in a temperature- and humidity-controlled automatic incubator. The results indicated that the aqueous latex solution increased vascular network formation compared to that with the negative control (p < 0.05) and the inhibitor control (p < 0.05). This suggests that under the experimental conditions tested, the aqueous latex solution induced an inflammatory response leading to neoangiogenesis.(AU)

Com o objetivo de analisar a atividade angiogênica apresentada pela Euphorbia tirucalli, popularmente conhecida comumente como “avelós”, foram realizados ensaios utilizando solução aquosa de látex na concentração de 10 mg/ml, aplicada em membrana corioalantóide (MCA) de 80 ovos férteis de galinha, incubado em estufa automática com temperatura e umidade controladas. Os resultados apontaram que a ação da solução aquosa provocou aumento da percentagem da rede vascular formada em relação aos controles negativo (p<0,05) e inibidor (p<0,05), indicando que nas condições deste experimento, foi responsável pela ativação da resposta inflamatória e crescimento de novos vasos sanguíneos.(AU)

Angiogenic activity of latex from Euphorbia tirucalliLinnaeus 1753 (Plantae, Euphorbiaceae) / Atividade angiogênica do látex da Euphorbia tirucalliLinnaeus 1753 (Plantae, Euphorbiaceae)

AbstractTo assess the pro-angiogenic activity of Euphorbia tirucalli, commonly known as “avelós” plant, we performed a series of tests by applying an aqueous E. tirucalli latex solution (10 mg/mL) to the chorioallantoic membranes (CAMs) of 80 fertilized chicken eggs incubated in a temperature- and humidity-controlled automatic incubator. The results indicated that the aqueous latex solution increased vascular network formation compared to that with the negative control (p < 0.05) and the inhibitor control (p < 0.05). This suggests that under the experimental conditions tested, the aqueous latex solution induced an inflammatory response leading to neoangiogenesis.

ResumoCom o objetivo de analisar a atividade angiogênica apresentada pela Euphorbia tirucalli, popularmente conhecida comumente como “avelós”, foram realizados ensaios utilizando solução aquosa de látex na concentração de 10 mg/ml, aplicada em membrana corioalantóide (MCA) de 80 ovos férteis de galinha, incubado em estufa automática com temperatura e umidade controladas. Os resultados apontaram que a ação da solução aquosa provocou aumento da percentagem da rede vascular formada em relação aos controles negativo (p<0,05) e inibidor (p<0,05), indicando que nas condições deste experimento, foi responsável pela ativação da resposta inflamatória e crescimento de novos vasos sanguíneos.

Análise fitoquímica e atividade fotoprotetora de extrato etanólico de Euphorbia tirucalli Linneau (Euphorbiaceae) / Phytochemical analysis and photoprotective activity of theethanolic extract of Euphorbia tirucalli Linneau (Euphorbiaceae)

RESUMO Euphorbia tirucalli Linneau, conhecida popularmente como "avelós", "cachorro pelado" ou "pau-pelado", é utilizada na medicina popular para o tratamento de câncer, antibiótico e antivirótico. As plantas medicinais são, frequentemente, utilizadas com o intuito de substituir ou auxiliar as terapias convencionais no tratamento de várias doenças, inclusive para evitar os malefícios causados por radiações ultravioletas. Com isso, o objetivo desta pesquisa foi avaliar o potencial fotoprotetor e a triagem fitoquímica do extrato etanólico das partes aéreas de avelós. A atividade fotoprotetora foi avaliada por meio de ensaios in vitro segundo o método adaptado de Mansur, utilizando extrato etanólico das partes aéreas. Os resultados obtidos mostraram que o estudo fitoquímico evidenciou a presença de açúcares redutores, alcaloides, fenóis, flavonoides, taninos, saponinas, esteroides e triterpenóides na fração etanólica. O extrato apresentou capacidade antioxidante (EC50) de 16,98 ± 0,35 µg.mL-1, teor de compostos fenólicos de 96,18 ± 1,33 mg EqAG/g e flavonoides de 63,57 ± 2,74 mg EqC/g que podem favorecer a atividade fotoprotetora. Avaliando o fator de proteção solar, pode-se observar que todas as concentrações testadas (0,01 a 0,1 µg.mL-1) apresentaram potencial de fotoproteção da radiação ultravioleta com variação de FPS de 6,05 a 19,84, respectivamente. Esses resultados sugerem que o extrato etanólico de Euphorbia tirucalli Linneau apresenta possível efeito fotoprotetor

ABSTRACT Euphorbia tirucalli Linneau, popularly known as "avelos", "naked cock" or "naked dog", is used in popular medicinein order to treat cancer, antibiotic and antiviral diseases. Herbal medicines are often employed in order to assist or replace conventional therapies for the treatment of several diseases, including the prevention of the damage caused by ultraviolet radiation. Thus, the aim of this research was to evaluate the photoprotective potential and phytochemical screening of the ethanol extract of the aerial parts of avelos. The photoprotective activity was assessed by in vitrotrials according to the method adapted from Mansur, using the ethanol extract of the aerial parts. The results showed that the phytochemical study revealed the presence of reducing sugars, alkaloids, phenols, flavonoids, tannins, saponins, steroids and triterpenoids in ethanolic fraction. The extract showed antioxidant activity (EC50) of 16,98 ± 0,35 µg.mL-1, phenolic contents of 96,18 ± 1,33 mg EqAG/g and 63,57 ± 2,74 flavonoids from mg EqC/g that can advantage the photoprotective activity. Assessing the sun protection factor, it can be observed that all the tested concentrations (0,01 to 0,1 µg.mL-1) showed potential for photoprotection from ultraviolet radiation with a range of 6,05 to 19,84 FPS, respectively. These results suggest that the ethanol extract of Euphorbia tirucalli Linneau presents possible photoprotective effect

Antifungal activity against Cryptococcus neoformans strains and genotoxicity assessment in human leukocyte cells of Euphorbia tirucalli L.

In the last times, focus on plant research has increased all over the world. Euphorbia tirucalli L., a plant known popularly as Aveloz, and originally used in Africa, has been drawing attention for its use in the United States and Latin America, both for use as an ornamental plant and as a medicinal plant. E. tirucalli L. is a member of the family Euphorbiaceae and contains many diterpenoids and triterpenoids, in particular phorbol esters, apparently the main constituent of this plant, which are assumed to be responsible for their activities in vivo and in vitro. The in vitro antifungal activities of Euphorbia tirucalli (L.) against opportunistic yeasts were studied using microbroth dilution assay. The results showed that aqueous extract and latex preparation were effective against ten clinical strains of Cryptococcus neoformans in vitro (Latex and extract MIC range of 3.2 - > 411 µg/mL). Aiming the safe use in humans, the genotoxic effects of E. tirucalli were evaluated in human leukocytes cells. Our data show that both aqueous extract and latex preparation have no genotoxic effect in human leukocytes cells in vitro. Although the results cannot be extrapolated by itself for use in vivo, they suggest a good perspective for a therapeutic application in future. In conclusion, our results show that the aqueous extract and latex preparation from E. tirucalli L. are antifungal agents effectives against several strains of C. neoformans and do not provoke DNA damage in human leukocyte cells, considering the concentrations tested.

Antifungal activity against Cryptococcus neoformans strains and genotoxicity assessment in human leukocyte cells of Euphorbia tirucalli L

In the last times, focus on plant research has increased all over the world. Euphorbia tirucalli L., a plant known popularly as Aveloz, and originally used in Africa, has been drawing attention for its use in the United States and Latin America, both for use as an ornamental plant and as a medicinal plant. E. tirucalli L. is a member of the family Euphorbiaceae and contains many diterpenoids and triterpenoids, in particular phorbol esters, apparently the main constituent of this plant, which are assumed to be responsible for their activities in vivo and in vitro. The in vitro antifungal activities of Euphorbia tirucalli (L.) against opportunistic yeasts were studied using microbroth dilution assay. The results showed that aqueous extract and latex preparation were effective against ten clinical strains of Cryptococcus neoformans in vitro (Latex and extract MIC range of 3.2 - > 411 µg/mL). Aiming the safe use in humans, the genotoxic effects of E. tirucalli were evaluated in human leukocytes cells. Our data show that both aqueous extract and latex preparation have no genotoxic effect in human leukocytes cells in vitro. Although the results cannot be extrapolated by itself for use in vivo, they suggest a good perspective for a therapeutic application in future. In conclusion, our results show that the aqueous extract and latex preparation from E. tirucalli L. are antifungal agents effectives against several strains of C. neoformans and do not provoke DNA damage in human leukocyte cells, considering the concentrations tested.

Antifungal activity against Cryptococcus neoformans strains and genotoxicity assessment in human leukocyte cells of Euphorbia tirucalli L.

In the last times, focus on plant research has increased all over the world. Euphorbia tirucalli L., a plant known popularly as Aveloz, and originally used in Africa, has been drawing attention for its use in the United States and Latin America, both for use as an ornamental plant and as a medicinal plant. E. tirucalli L. is a member of the family Euphorbiaceae and contains many diterpenoids and triterpenoids, in particular phorbol esters, apparently the main constituent of this plant, which are assumed to be responsible for their activities in vivo and in vitro. The in vitro antifungal activities of Euphorbia tirucalli (L.) against opportunistic yeasts were studied using microbroth dilution assay. The results showed that aqueous extract and latex preparation were effective against ten clinical strains of Cryptococcus neoformans in vitro (Latex and extract MIC range of 3.2 - > 411 µg/mL). Aiming the safe use in humans, the genotoxic effects of E. tirucalli were evaluated in human leukocytes cells. Our data show that both aqueous extract and latex preparation have no genotoxic effect in human leukocytes cells in vitro. Although the results cannot be extrapolated by itself for use in vivo, they suggest a good perspective for a therapeutic application in future. In conclusion, our results show that the aqueous extract and latex preparation from E. tirucalli L. are antifungal agents effectives against several strains of C. neoformans and do not provoke DNA damage in human leukocyte cells, considering the concentrations tested.

Identification of Phenolic Compounds and Evaluation of Antioxidant and Antimicrobial Properties of Euphorbia Tirucalli L.

Bioactive compounds extracted from natural sources can benefit human health. The aim of this work was to determine total phenolic content and antioxidant activity in extracts of Euphorbia tirucalli L. followed by identification and quantification of the phenolic compounds, as well as their antibacterial activities. Antioxidant activities were determined by DPPH and ABTS(•+) assay. Identification of phenolic compounds was performed using high-performance liquid chromatography (HPLC), and antimicrobial activities were verified by agar dilution methods and MIC values. Total phenolic content ranged from 7.73 to 30.54 mg/100 g gallic acid equivalent. Extracts from dry plants showed higher antioxidant activities than those from fresh ones. The DPPH EC50 values were approximately 12.15 µg/mL and 16.59 µg/mL, respectively. Antioxidant activity measured by the ABTS method yielded values higher than 718.99 µM trolox/g for dry plants, while by the Rancimat(®) system yielded protection factors exceeding 1 for all extracts, comparable to synthetic BHT. Ferulic acid was the principal phenolic compound identified and quantified through HPLC-UV in all extracts. The extracts proved effective inhibitory potential for Staphylococcus epidermidis and Staphylococcus aureus. These results showed that extracts of Euphorbia tirucalli L. have excellent antioxidant capacity and moderate antimicrobial activity. These can be attributed to the high concentration of ferulic acid.

The crude latex of Euphorbia tirucalli modulates the cytokine response of leukocytes, especially CD4+ T lymphocytes

The plants of the Euphorbiaceae family, especially those of the genus Euphorbia, are frequently used by Brazilian folk communities to treat a wide variety of infectious, tumoral and inflammatory illnesses. Among the species of this genus, Euphorbia tirucalli L. is widely used in some Brazilian regions, such as the Jequitinhonha River Valley. There is evidence that the latex produced by E. tirucalli has antiviral and antitumor activities, but little is known about the mechanisms involved in these effects. It is likely that the mechanism for such activities involves leukocyte activation and cytokine production. In this work, we aimed to evaluate the production of type 1 (TNF-α and IFN-γ) and type 2 (IL-4 and IL-10) cytokines by circulating leukocyte subsets submitted to brief stimulation with the crude latex of E. tirucalli. Peripheral blood leukocytes of twenty healthy subjects were submitted to 4 h incubation with crude E. tirucalli latex diluted in dimethylsulfoxide. After the incubation period, the cells were stained with FITC-conjugated monoclonal antibodies specific to the cell surface receptors CD4, CD8 and CD14, and to PE-conjugated monoclonal antibodies specific to the cytokines TNF-α, IFN-γ, IL-4 and IL-10. The acquisition and analysis of data were performed by flow cytometry. The results showed a significant increase (p<0.05) in the percentage of CD4+ T lymphocytes positive for the type 1 cytokines TNF-α and IFN-γ. Neutrophils and CD8+ T lymphocytes showed a mixed profile of cytokine production, characterized by an increase in the percentage of cells expressing IFN-γ, TNF-α, and IL-10. The data indicate a predominant type 1 cytokine response. The findings presented suggest that the effect popularly attributed to E. tirucalli usage may be attributed to its effect on the production of TNF-α and IFN-γ. However, the relationship between the in vitro and in vivo effects of E. tirucalli needs to be investigated.

Physical chemical and citotoxic evaluation of highly diluted solutions of Euphorbia tirucalli L. prepared through the fifty milesimal homeopathic method / Avaliação físico-química e citotóxica de soluções altamente diluídas de euphorbia tirucalli l. Preparada pelo método cinqüenta milesimal (lm) / Evaluación físico-química y citotóxica de soluciones altamente diluídas de Euphorbia tirucalli L. preparadas por el método homeopático cincuenta milesimal (LM)

Motivação: Embora Hahnemann tenha descrito o método LM na 6ª. Edição do Organon da Arte de Curar, poucas pesquisas tem sido feitas sobre as propriedades físico-químicas destas preparações. Além disso, ainda não existem evidências que apontem para a correlação entre propriedades físico-químicas e os efeitos biológicos das altas diluições. Objetivos: determinar características físico-químicas das preparações LM tais como condutividade elétrica, pH e índice de refração, bem como o efeito biológico em modelos experimentais. Materiais e Métodos: foi analisada uma série de diluições desde 1 lm até 10 lm de Euphorbia tirucalli L., preparada a partir do látex e do suco da planta. Para considerar as características sazonais desta planta, usamos 2 populações diferentes, colhidas uma em Junho de 2007 e outra em Maio de 2008. Além disso, o efeito citotóxico da Euphorbia tirucalli L. 5 lm foi testado em células humanas cancerosas (MCF7) através de ensaio MTT. Conclusões: Algumas diferenças entre as duas populações foram observadas. No entanto, nenhuma correlação clara pode ser observada entre as propriedades físico-químicas e a atividade biológica.

Background: although Hahnemann described the fifty-milesimal (LM) method in the 6th edition of the Organon of the Medical Art, very little research has been carried out on the physical chemical properties of these homeopathic preparations. Furthermore, there is still no evidence allowing for the correlation between the alleged physical chemical properties and the biological effects of high dilutions. Aims: to evaluate physical chemical characteristics of LM preparations including electrical conductivity, pH and refraction index, and their effect on biological experimental models. Materials and methods: preparations tested for physical chemical analysis were dilutions 1 lm to 10 lm of Euphorbia tirucalli L. prepared from the latex and the juice of the plant. To rule the seasonal characteristics of this plant, 2 different populations were used, one collected in June 2007 and the other in May 2008. Furthermore, the cytotoxic effect of Euphorbia tirucalli 5 lm was tested on human breast cancer cells (MCF7) through MTT assay. Conclusions: Some differences among the two collections were observed. However, any clear correlation could be observed between physical chemical properties and biological activity.

Motivación: Aunque Hahnemann describió el métodocincuenta milesimal (LM) en la 6 ª edición del Organon del Arte Médica, muy poca investigación se ha realizado sobre las propiedades físico-químicas de estos preparados homeopáticos. Por otra parte, todavía no hay pruebas que permitan la correlación entre las presuntas propiedades físico-químicas y los efectos biológicos, de las altas diluciones. Objetivos: evaluar las características físico-químicas de los preparados LM, incluyendo conductividad eléctrica, pH y el índice de refracción, y su efecto en modelos biológicos experimentales. Materiales y métodos: las muestras para el análisis físico-químico fueron diluciones 1 a 10 lm de Euphorbia tirucalli L. preparadas a partir del látex y el jugo de la planta. Para descartar las características sazonales de esta planta, dos poblaciones diferentes fueron utilizadas, una recogida en junio de 2007 y otro en mayo de 2008. Además, el efecto citotóxico de Euphorbia tirucalli 5 lm fue probado en células humanas de cáncer de mama (MCF7) a través del ensayo MTT. Conclusiones: Algunas diferencias entre las dos colecciones se observaron. Sin embargo, ninguna correlación clara se observó entre las propiedades físicas- químicas y actividad biológica.