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.

Cicatrização gástrica com uso do extrato da Euphorbia Tirucalli L.: estudo em ratos / Gastric healing process with raw extract of Euphorbia tirucalli L.: study in rats

RACIONAL: A utilização de plantas na prevenção e no tratamento de doenças é prática milenar. O aveloz (Euphorbia tirucalli) é uma planta originária da África e tem sido relacionada com efeitos antimicrobiano, antiulceroso, anticarcinogênico, antivirais, cicatrizante, antihelmíntico e antisifilítico. OBJETIVO: Avaliar o uso do extrato bruto de Euphorbia tirucalli no processo de cicatrização de estômago de camundongo. MÉTODOS: Dezesseis camundongos da espécie Swiss, adultos, fêmeas foram submetidos à incisão longitudinal de 1 cm no corpo gástrico e síntese em plano único com pontos separados de polipropilene 6-0. Após o procedimento os animais foram distribuídos aleatoriamente em dois grupos de oito. Eles foram redistribuídos em quatro subgrupos: Aveloz (GA7) e Controle (GC7) com morte programada para 7º dia de pós-operatório e Aveloz (GA14) e Controle (GC14) com morte programada para 14º dia de pós-operatório. No seguimento o grupo GA utilizou-se 1 mL de solução hidroalcoólica do extrato bruto de Euphorbia tirucalli L. na concentração de 30 mg/ml por via oral através de gavagem e no GC, soro fisiológico 0,9%, no mesmo volume e via. Após a morte, foi realizado o inventário da cavidade abdominal e procedeu-se a retirada do estômago, fixação no formol e enviado para a análise microscópica. Na análise comparativa entre os dois grupos foram avaliados parâmetros macroscópicos e microscópicos da cicatrização. RESULTADOS: Não foram detectados sinais de peritonite, fístulas ou hematomas nos animal. Houve aderências do estômago, principalmente, com o fígado e omento, nos animais dos 7º e 14º dias do período pós-operatório nos dois grupos. A análise dos parâmetros histológicos não demonstrou diferença estatisticamente significante em nenhum dos parâmetros avaliados. CONCLUSÃO: A avaliação do uso do extrato bruto de Euphorbia tirucalli L. em cicatrização de lesões em estômago de camundogos mostrou equivalência em comparação ao grupo controle.

BACKGROUND: The use of plants in the prevention and treatment of disease is age-old practice. The aveloz (Euphorbia tirucalli) is a plant native of Africa and has been associated with antimicrobial, antiulcers, anticarcinogenic, antiviral, healing, anti-helminthic, antisiphilitic effects. AIM: To analyze the effect of the crude extract of Euphorbia tirucalli L. in the stomach healing process of mice. METHODS: Sixteen Swiss mice, adult females were subjected to 1 cm longitudinal incision in the gastric body and sutured with 6-0 polypropylene stitches. After the procedure, the animals were randomly divided into two groups of eight animals. These were redistributed into four subgroups: Aveloz (GA7) and Control (CG7) with programmed death for 7th day postoperatively and Aveloz (GA14) and Control (GC14) with programmed death for 14 days postoperatively. The group GA used 1 ml of hydroalcoholic solution of the crude extract of Euphorbia tirucalli at 30 mg/ml orally by gavage route and the CG, 0.9% saline solution at the same volume and route. After death, the inventory of the abdominal cavity was conducted and the stomach removal was performed, fixing in formalin and sent for microscopic analysis. In the comparative analysis between the two groups were evaluated the macroscopic and microscopic parameters of healing. RESULTS: There were no signs of peritonitis, fistulas or hematomas in the animals. There were adhesions of the stomach, especially with the liver and omentum in the animals at 7 and 14 days postoperatively in both groups. The analysis of histological parameters showed no statistically significant difference between groups in any of the parameters evaluated. CONCLUSION: The evaluation of the use of the crude extract of Euphorbia tirucalli L. on stomach wound healing in mice showed equivalence in comparison to the control group.

Avaliação da condutividade elétrica, pH e índice de refração como parâmetro físico-químico para controle de altas diluições de aveloz, em farmácias homeopáticas / Evaluation of electrical conductivity, pH and refractive index as physico-chemical parameters for quality control of Aveloz homeopathic solutions

Euphorbia tirucalli Lineu (aveloz) pertence à família Euphorbiaceae e é usada no tratamento do câncer e de verrugas. Alguns trabalhos têm evidenciado que os ésteres de forbol são os princípios ativos responsáveis pela atividade antitumoral do aveloz. A produção destas moléculas ocorre em maior quantidade no mês de maio, durante o período da manhã. O presente estudo teve como objetivo avaliar se os parâmetros físico-químicos de soluções aquosas ultradiluídas e dinamizadas (SUDs) de aveloz, como: pH, condutividade elétrica e índice de refração se alteram devido ao tempo de estocagem. As SUDs foram preparadas seguindo método de trituração em lactose e posterior solubilização em meio aquoso, como descrito na Farmacopéia Homeopática Brasileira 2ª Edição, utilizando como insumo de partida o látex coletado da planta no mês de maio. SUDs contendo apenas lactose foram preparadas e avaliadas igualmente àquelas contendo aveloz, como grupo controle. As potências que foram submetidas às análises de condutividade elétrica, pH e índice de refração foram: 4CH, 7CH, 9CH, 12CH, 14CH, 15CH, 29CH, 30CH. Como resultados, detectamos diferença estatisticamente significativa (p = 0,035) para os valores de condutividade elétrica obtidos de SUDs contendo apenas lactose em comparação as SUDs de aveloz, na potência 15CH. Verificamos também, que a condutividade elétrica de soluções aquosas dinamizadas aumenta com o envelhecimento das mesmas;entretanto, variações na condutividade elétrica não estão diretamente relacionadas com o pH ou o índice de refração das soluções, indicando que o processo de preparo das soluções pode modificar a condutividade elétrica das SUDs de maneira independente. A presença de gases no interior dos vidros que armazenam as SUDs parece influenciar a condutividade elétrica destas soluções. Para as medidas de pH e índice de refração nenhuma diferença estatisticamente significativa foi observada (p>0,05).(AU)

Evaluation of the genotoxic and mutagenic potentials of phytotherapic and homeopathic solutions of Euphorbia tirucalli Lineu (Aveloz) / Evaluation of the genotoxic and mutagenic potentials of phytotherapic and homeopathic solutions of Euphorbia tirucalli Lineu (Aveloz)

Introduction: Euphorbia tirucalli Lineu, commonly known as Aveloz, is a very common plant found in tropical regions [1]. The ingestion or contact with its latex causes symptoms such as vomiting and diarrhea, pallor, skin irritation, hepatotoxicity as well as carcinogenesis [2]. Moreover, the Aveloz latex is also responsible for a few important activities against some infectious and neoplastic diseases. Aveloz latex phytochemical composition may vary according to seasonal aspects and geographic location [3], and it is used either orally or topically in traditional medicine. Popularly known as an antitumoral agent (breast, prostate, lung, kidney), it is used not only in Brazil, but in several other countries. According to the literature, the latex could have a dual behaviour, activating or inhibiting tumoral events [3-6]. However, there are few reports discussing these mechanisms. Besides, the mutagenic and genotoxic potentials of phytochemical and homeopathic Aveloz have not yet been described. Several experimental methods have been used to evaluate the mutagenic and genotoxic effects, such as Inductest, the Ames test and the chromotest. Objective: This study aims to evaluate the genotoxic and mutagenic potentials of Aveloz latex and Aveloz phytotherapic and homeopathic solutions. Methodology: In this study, Aveloz 5 and 30cH are prepared according to Brazilian Homeopathic Pharmacopoeia [7], from Aveloz latex collected in the Center for Natural Products Research (NPPN) at the Universidade Federal do Rio de Janeiro [8]. The Aveloz phytochemical solution was prepared following the doses used in folk medicine: 2 drops diluted in 250ml of water and 2 drops diluted in 25 ml of water. All test solutions were submitted to the following methodologies: (a) Inductest: assesses the ability of physical or chemical agents to promote lysogenic induction as a response to DNA damage in lysogenic bacteria; (b) The Ames test: uses indicator strains of Salmonella typhimurium, which are sensitive to substances that can induce different types of mutation; (c) Chromotest: evaluates the genotoxicity of chemicals through the induction of the bacterial SOS system. Results: In the Inductest there was no decrease in bacterial survival fraction and no increase in lysogenic cycle. As measured by The Ames test and the chromotest no mutagenic or genotoxic potentials were detected. Discussion: The homeopathic and the phytochemical Aveloz solutions were unable to produce lysogenic induction or mutagenesis in bacterial cells and they were also unable to produce genotoxic effects, as measured by chromotest. Conclusion: Our results showed that no mutagenic or genotoxic damages were induced by all Aveloz preparations studied, thus we are led to believe that patients using Aveloz as a complementary therapy present no side effects in relation to mutagenesis and genotoxicity. (AU)

Evaluation of the genotoxic and mutagenic potentials of phytotherapic and homeopathic solutions of Euphorbia tirucalli Lineu (Aveloz) / Evaluation of the genotoxic and mutagenic potentials of phytotherapic and homeopathic solutions of Euphorbia tirucalli Lineu (Aveloz)

Introduction: Euphorbia tirucalli Lineu, commonly known as Aveloz, is a very common plant found in tropical regions [1]. The ingestion or contact with its latex causes symptoms such as vomiting and diarrhea, pallor, skin irritation, hepatotoxicity as well as carcinogenesis [2]. Moreover, the Aveloz latex is also responsible for a few important activities against some infectious and neoplastic diseases. Aveloz latex phytochemical composition may vary according to seasonal aspects and geographic location [3], and it is used either orally or topically in traditional medicine. Popularly known as an antitumoral agent (breast, prostate, lung, kidney), it is used not only in Brazil, but in several other countries. According to the literature, the latex could have a dual behaviour, activating or inhibiting tumoral events [3-6]. However, there are few reports discussing these mechanisms. Besides, the mutagenic and genotoxic potentials of phytochemical and homeopathic Aveloz have not yet been described. Several experimental methods have been used to evaluate the mutagenic and genotoxic effects, such as Inductest, the Ames test and the chromotest. Objective: This study aims to evaluate the genotoxic and mutagenic potentials of Aveloz latex and Aveloz phytotherapic and homeopathic solutions. Methodology: In this study, Aveloz 5 and 30cH are prepared according to Brazilian Homeopathic Pharmacopoeia [7], from Aveloz latex collected in the Center for Natural Products Research (NPPN) at the Universidade Federal do Rio de Janeiro [8]. The Aveloz phytochemical solution was prepared following the doses used in folk medicine: 2 drops diluted in 250ml of water and 2 drops diluted in 25 ml of water. All test solutions were submitted to the following methodologies: (a) Inductest: assesses the ability of physical or chemical agents to promote lysogenic induction as a response to DNA damage in lysogenic bacteria; (b) The Ames test: uses indicator strains of Salmonella typhimurium, which are sensitive to substances that can induce different types of mutation; (c) Chromotest: evaluates the genotoxicity of chemicals through the induction of the bacterial SOS system. Results: In the Inductest there was no decrease in bacterial survival fraction and no increase in lysogenic cycle. As measured by The Ames test and the chromotest no mutagenic or genotoxic potentials were detected. Discussion: The homeopathic and the phytochemical Aveloz solutions were unable to produce lysogenic induction or mutagenesis in bacterial cells and they were also unable to produce genotoxic effects, as measured by chromotest. Conclusion: Our results showed that no mutagenic or genotoxic damages were induced by all Aveloz preparations studied, thus we are led to believe that patients using Aveloz as a complementary therapy present no side effects in relation to mutagenesis and genotoxicity.