Toxicological and anti-inflammatory profile of Synadenium grantii Hook. f. in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Synadenium grantii Hook. f., popularly known as "janaúba" or "leiterinha", is used in the folk medicine to treat gastric disorders, some types of neoplasias and inflammatory diseases. AIM OF THE STUDY: The aim of this study was to show the anti-inflammatory activity of the methanol extract obtained from S. grantii stems and also certify the safety of the extract performing toxicological analysis. MATERIAL AND METHODS: The anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally pre-treated with the S. grantii extract (1, 3 or 10 mg/kg). The leukocyte influx (optical microscopy) and secretion of chemical mediators (TNF, IL-6 and IL-1ß, by enzyme-linked immunosorbent assay) were quantified in the inflamed exudate. The toxicity was investigated using the dose-fixed procedure (acute toxicity) and repeated dose 28-day (subacute toxicity) in mice orally treated with S. grantii extract. The open field and rota-rod test were used to evaluate possible interference of adverse effect of S. grantii on motor coordination, locomotor and exploratory activity. RESULTS: The analysis of the inflammatory exudate of S. grantii-treated mice demonstrated reduction in the polymorphonuclear cells (PMN) migration to the inflamed tissue, as well as the reduction of the pro-inflammatory cytokines TNF and IL-1ß. Furthermore, the acute and sub-acute toxicity studies did not show significant changes in body weight, general behaviour, biochemical parameters, organ weight and liver and kidney histopathological analysis. However, animals acutely treated with S. grantii presented reduction in the number of crosses in relation to the vehicle group, without significant difference in the number of elevations and latency time between the groups in rota-rod test. The obtained results allow to set the NOAEL (Non-observed-adverse-effect level) in 100 mg/kg for this specie of rodent. CONCLUSIONS: Together, the results herein obtained show that S. grantii extract presented anti-inflammatory activity by decreasing the influx of PMN to the inflamed tissue, as well as the cytokines TNF and IL-1ß levels. In addition, S. grantii extract seemed not to present significant acute or subacute toxicity when administered to mice, demonstrating for the first time the safety of this extract, when orally administered.

Antiprotozoal, antimycobacterial, and anti-inflammatory evaluation of Cnidoscolus chayamansa (Mc Vaugh) extract and the isolated compounds.

Cnidoscolus chayamansa is a medicinal and edible plant known as Chaya, is commonly used as an anti-inflammatory, antiprotozoal, antibacterial agent and as a remedy for respiratory illness, gastrointestinal disorders, and vaginal infections related with the inflammation process. In this paper, we describe the plant's phytochemical analysis and biological activities (antimycobacterial, antibacterial, antiprotozoal, and anti-inflammatory properties) of the CHCl3:MeOH (1:1) leaves extract and isolated compounds, as well as the acute and sub-acute toxic effects. Chemical identification of isolated compounds was performed by 1H- and 13C NMR spectra data. In vitro antibacterial and antimycobacterial activities were determined by disc diffusion and MABA assays, respectively; antiprotozoal test by means of the sub-culture test. Topical and systemic anti-inflammatory effects were tested by TPA and carrageenan assay on BALB/c mice. Moretenol, moretenyl acetate, kaempferol-3,7-dimethyl ether, and 5-hydroxy-7-3',4'-trimethoxyflavanone were the main compounds isolated. The CHCl3:MeOH extract showed antiprotozoal (IC50≤65.29µg/mL), antimycobacterial (MIC≤50µg/mL), and anti-inflammatory activities (ED50=1.66mg/ear and 467.73mg/kg), but was inactive against the bacterial strains tested. The LD50 for extract was >2g/kg. In the sub-acute toxicity test, the extract was administered at 1g/kg for 28days and did not cause lethality or any alteration in hematological and biochemical parameters; in addition, liver, kidney, and spleen histological analysis exhibited no structural changes. Moretenol and moretenyl acetate showed MIC=25µg/mL against Mycobacterium tuberculosis H37Rv and against four monoresistant strains of M. tuberculosis H37Rv. Both compounds exhibited moderate activity against Entamoeba histolytica and Giardia lamblia (IC50≤71.70µg/mL). Kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3',4'-trimethoxy-flavanone were more active than the extract against E. histolytica and G. lamblia, showing IC50 ≤27.43µg/mL. As topical anti-inflammatory agents, moretenol and kaempferol-3,7-dimethyl ether were the most active compounds inhibiting the edema in 30.52 and 26.67%, respectively. Moretenol and moretenyl acetate showed significant antimycobacterial and antiprotozoal activities; in addition, important antiprotozoal effect was detected with kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3',4'-trimethoxyflavanone. The extract and the terpenoids possess good anti-inflammatory activity. The extract did not produce lethality or adverse effects in acute and sub-acute tests.

Aspectos botânicos e clínicos das intoxicações por plantas das Famílias Araceae, Euphorbiaceae e Solanaceae no Estado de Pernambuco / Bothanical and clinical aspectos of intoxications caused by plants of the Araceae, Euphorbiaceae and Solanaceae family in the state of Pernambuco

Trata-se de um estudo investigativo sobre os aspectos botânicos e clínicos das intoxicações humanas provocadas por espécies das famílias Araceae, Euphorbiaceae e Solanaceae. É um estudo transversal, descritivo, com abordagem quantitativa, aprovado pelo Comitê de Ética do Hospital da Restauração. Os dados referentes ao período de 1992 a 2009 foram coletados no Centro de Assistência Toxicológica de Pernambuco (CEATOX). Dos 214 prontuários analisados, 140 tiveram diagnóstico de intoxicação por espécies das famílias Araceae (55%; n=77); Euphorbiaceae (36,43%; n=51) e Solanaceae (8,57%; n=12). A maioria das Araceae foi representada por Dieffenbachia amoena Bull (50%); Euphorbiaceae por Manihot esculenta Crantz (11,42%) e Solanaceae por Brugmansia suaveolens (Willd.) Bercht. & J. Presl. (5,71%), utilizadas como ornamental, alimentícia, medicinal, em brincadeiras infantis e suicídio. Em consequência da ingestão de partes dessas plantas os sintomas apresentados foram: edema (língua, lábio), náusea, diarreia, rubor facial, midríase, alucinações e dores abdominais. O tratamento constou de observação clínica (45,31%) e tratamento sintomático (40,18%). A gravidade das intoxicações foi classificada como aguda moderada em 79,69% dos pacientes.(AU)

This is an investigative study about the clinical and botanical aspects of human poisoning caused by plants of the species Araceae, Euphorbiaceae and Solanaceae. It is a cross-sectional descriptive study with a quantitative approach, approved by the Restoration Hospital Ethics Committee. Data was collected at the Toxicological Assistance Centre of Pernambuco (CEATOX) comprising the period of 1992 to 2009. 214 records were analyzed, 140 had an intoxication diagnostic from the families: Araceae (55%, n = 77); Euphorbiaceae (36,43%; n = 51) and solanaceae (8,57%; n = 12). Aracea was majorly represented by Dieffenbachia Amoena Bull (50%); Euphorbiaceae by Manihot esculenta Crantz (11,42%) and Solanaceae by Brugmansia suaveolens (Willd.) Bercht. & J. Presl. (5, 71%) that were used as ornamental plants, food, medicine, in children's play and suicide attempts. As a result of ingestion of parts of the plant the symptoms were edema (tongue, lips), nausea, diarrhea, facial flushing, mydriasis, hallucinations and abdominal pain. Treatment consisted of clinical observation (45,31%) and symptomatic treatment (40,18%). The severity of the intoxications was classified as 'moderate acute' in 79,69% of patients.(AU)

Cleistanthus collinus poisoning: experience at a medical intensive care unit in a tertiary care hospital in south India.

BACKGROUND & OBJECTIVES: Ingestion of Cleistanthus collinus causes hypokalemia and cardiac arrhythmias leading to mortality in most cases. We undertook this retrospective study to evaluate the clinical presentation and predictors of outcome in critically ill patients admitted with C. collinus poisoning. METHODS: The case records of 56 patients admitted to the medical intensive care unit (MICU) of a tertiary care teaching hospital in south India (2000-2014) with C. collinus poisoning were retrospectively analysed. RESULTS: The mean age of patients was 36.7±13.3 yr; there were 30 males. Salient clinical manifestations included hypokalemia (58%), neutrophilic leucocytosis (48.2%), acute kidney injury (AKI) (42.9%), acute respiratory failure requiring mechanical ventilation (AcRFMv) (32.1%), shock (21.4%); cardiac arrhythmias and neuromuscular weakness (19.6% each); 21 patients (37.5%) had adverse outcome. Longer time-lapsed from consumption to reaching emergency room [median (interquartile range)] (hours) [49 (22-97) vs. 28 (7-56), p =0.0380 ]; higher acute physiology and chronic health evaluation II (APACHE II) score at presentation [14 (8.25-14.75) vs. 2 (0-6) P<0.001]; and presence of the following [odds ratio (95% confidence intervals)] at initial presentation: shock [37.40 (4.29-325.98), P=0.001]; AcRFMv [26.67 (5.86-121.39), P<0.001]; elevated alanine aminotransferase [5.71 (1.30-25.03), p0 =0.021]; metabolic acidosis [5.48 (1.68-17.89), P=0.005]; acute kidney injury (AKI) [5 (1.55-16.06), P=0.007]; hyponatremia [4.67 (1.25-17.44), P=0.022]; and neutrophilic leucocytosis [3.80 (1.02-14.21), P=0.047] predicted death. A significant (P<0.001) increasing trend in mortality was observed with increasing International Program on Chemical Safety Poisoning Severity Score (IPCS-CSS) grade. INTERPRETATION & CONCLUSIONS: C. collinus is a lethal poison associated with high mortality for which there is no specific antidote. Careful search and meticulous monitoring of the predictors of death and initiating appropriate corrective measures can be life saving.

Quantitative analysis of biomarkers of liver and kidney injury in serum and urine using ultra-fast liquid chromatography with tandem mass spectrometry coupled with a hydrophilic interaction chromatography column: Application to monitor injury induced by Euphorbiae pekinensis Radix.

Fast and sensitive monitoring of drug-induced liver and kidney injury in early stage is beneficial. An ultrafast liquid chromatography with tandem mass spectrometry assay was developed and validated to simultaneously determine ten endogenous biomarkers in serum and urine, including hippuric acid, phenylacetylglycine, 5-oxoproline, cholic acid, taurine, indoleacetic acid, 3-indoxyl sulfate, guanidinosuccinic acid, guanidinoacetic acid and uric acid. A CAPCELL CORE PC column (2.1 × 150 mm, 2.7 µm) was adopted for analytes separation. Gradient elution was performed with acetonitrile and water containing 5 mM ammonium acetate. Simple protein precipitation was applied in sample preparation. Good linearities were achieved with all the regression coefficients above 0.9911. Accuracy was 2.9-14.2% in serum and 4.1-14.6% in urine. The mean recovery was above 70% with acceptable matrix effects. The method was applied to monitor injury induced by Euphorbiae pekinensis Radix with a subacute rats model. All the biomarkers showed obvious concentration changes during the injury period. Furthermore, several biomarkers showed significant changes in earlier stage when compared with the current clinical serum bio-parameters. The method might be helpful for early diagnosis of drug induced liver and kidney injury in clinical after tested on more drugs.

Phytochemical Characteristics of Seeds and Its Effects on the Intestinal Motility and Toxicity of Joannesia princeps.

Joannesia princeps is a plant commonly used in folk medicine as laxative for menstrual discomfort and as antihelminthic and antimicrobial to reduce edema and improve tissue healing. The seeds are used in many regions of Brazil as laxative; however, studies are needed to confirm its effectiveness and safety. Thus, the aim of this study was to evaluate the effects of using seeds of this plant on intestinal motility of Wistar rats, evaluate the effects and acute toxicity of its management, as well as determine its phytochemical profile. The evaluation of the effect on the intestinal motility was performed according to the model described by Michelin and Salgado (2004) with modifications. For the evaluation of acute toxicity, we used the model described by Craveiro et al. (2008) and Goloni et al. (2005), and for the analysis of the presence of alkaloids, flavonoids, anthraquinones, steroids, and other components, we used the method described by Carvalho et al. (2006). The results showed that J. princeps exhibits laxative effects similar to those of Senna species such as Cassia angustifolia and the phytochemical analysis of ethanol and aqueous extracts showed the presence of alkaloids, triterpenes, and/or steroids compounds. Acute toxicity showed in the first 12 h: piloerection, contortion, decreased respiratory rate, diarrhea, and weight loss. After this period, these changes were no longer observed. It was concluded that the seeds of this plant have potential laxative activity, confirming the popular use and that the dose of 5 g/kg can be considered safe for consumption.

[Concentrations of alkaloids, cyanogenic glycosides, polyphenols and saponins in selected medicinal plants from Ecuador and their relationship with acute toxicity against Artemia salina]. / Concentraciones de alcaloides, glucósidos cianogénicos, polifenoles y saponinas en plantas medicinales seleccionadas en Ecuador y su relación con la toxicidad aguda contra Artemia salina.

Alkaloids, polyphenols, cyanogenic glycosides and saponins are among the main chemical compounds synthesized by plants but not considered essential for their basic metabolism. These compounds have different functions in plants, and have been recognized with medicinal and pharmacological properties. In this research, concentrations of the mentioned secondary metabolites were determined in the medicinal plants Artemisia absinthium, Cnidoscolus aconitifolius, Parthenium hysterophorus, Piper carpunya and Taraxacum officinale, from Ecuador, and related with cytotoxic effects against Artemia salina. Alcoholic and aqueous extracts from leaves of these selected plants were prepared at different concentrations. To assess cytotoxicity of these extracts, different bioassays with A. salina were undertaken, and the mortality rates and LC50 were obtained. Besides, concentrations of alkaloids, cyanogenic glycosides, phenols, tannins and saponins were determined by spectrophotometric methods; this constituted the first report of quantification of secondary metabolites in the selected plants from Ecuador. T. officinale had the highest concentration of total phenols (22.30 ± 0.23 mg/g) and tannins (11.70 ± 0.10 mg/g), C. aconitifolius of cyanogenic glycosides (5.02 ± 0.37 µg/g) and P. hysterophorus of saponins (6.12 ± 0.02 mg/g). Tannins values obtained were not adverse to their consumption. Alcoholic and aqueous extracts of selected plants had hemolytic activity depending on the concentration of saponins. Although the values of cyanogenic glycosides were permissible, it was necessary to monitor the presence of this metabolite in plants to minimize health problems. LC50 values ranged from extremely toxic (3.37 µg/mL) to highly toxic (274.34 µg/mL), in P. carpunya and T. officinale, respectively. From correlation analysis, it was observed that increase values of alkaloids concentrations had highly significant (p<0.001) acute toxicity against A. salina, while at a higher polyphenol concentration the level of plants cytotoxicity decreased significantly (p<0.001). The results of principal component analysis showed that saponins apparently were in synergy with polyphenols to decrease cytotoxicity, but antagonize with alkaloids and cyanogenic glycosides, indicating that these secondary metabolites present variability in the mechanisms of action against A. salina, as cytotoxic compounds. These results also demonstrate that polyphenols and saponins can be lethal at low concentrations, demonstrating the potential of brine shrimp bioassay as a model to evaluate plant extracts containing low concentrations of chemical compounds with high polarities. The significant positive correlation between cytotoxicity and concentration of alkaloids confirmed by the bioassay of brine shrimp can be useful to identify promising sources of antitumor compounds, and to evaluate tolerable limits not affecting other benign cells. Contents of secondary metabolites found in the selected plants confer them great pharmacologic values.

Possibilidades terapêuticas e risco toxicológico de Jatropha gossypiifolia L: uma revisão narrativa / Therapeutic possibilities and toxicological risk of Jatropha gossypiifolia L: a narrative review

A espécie Jatropha gossypiifolia L. (Euphorbiaceae), popularmente conhecida como pião-roxo, entre tantos outros nomes, é um bom exemplo do tênue limiar que separa o efeito terapêutico do tóxico. Apesar de ser classicamente conhecida como planta tóxica possui usos na medicina popular. Alguns desses efeitos têm sido comprovados em estudos experimentais, como os de antimicrobiano, antineoplásico, cicatrizante e hipotensor, sendo possivelmente explicados pela presença de substâncias como alcalóides, terpenóides, flavonóides, lignanas e taninos. Esta revisão aborda aspectos importantes, com ênfase na toxicidade crônica dessa espécie, de modo a servir de fonte de informação aos interessados em avaliar a relação risco/benefício do uso terapêutico de Jatropha gossypiifolia L.

The species Jatropha gossypiifolia L. (Euphorbiaceae), popularly known as bellyache bush, among several other names, is an important example of the tenuous threshold that separates the therapeutic from the toxic effect. Although traditionally known as a toxic plant, it has been used in folk medicine. Some of its effects have been proved by experimental studies as antimicrobial, antineoplastic, healing and hypotensive, likely explained by the presence of substances such as alkaloids, terpenoids, flavonoids, lignans and tannins. This review deals with important aspects, focusing on the chronic toxicity of this species, in order to serve as an information source for those interested in evaluating the risk-benefit ratio of the therapeutic use of Jatropha gossypiifolia L.

Avaliação da atividade moluscicida do látex de três espécies de Euphorbia (Euphorbiaceae) sobre Leptinaria unilamellata d'Orbigny, 1835 (Gastropoda - Subulinidae) / Assessment of moluscicidal activity of the latex of three Euphorbia (Euphorbiaceae) species on Leptinaria unilamellata d'Obigny 1835 (Gastropoda - Subulinidae)

Gastrópodes pulmonados terrestres podem atuar como hospedeiros intermediários de helmintos. Os primeiros registros do controle químico desses invertebrados datam do início do século XX e as substâncias utilizadas eram toxinas inespecíficas já empregadas no controle de outras pragas. Moluscicidas sintéticos apresentam limitações técnicas que estimularam a busca de substitutos naturais. Dentre as várias espécies vegetais com atividade moluscicida, Euphorbia cotinifolia L., Euphorbia milii des Moul. var. splendens (Bojer ex Hook) Ursch & Leandri e Euphorbia tirucalli L. despertam atenção pelos excelentes resultados obtidos sobre moluscos aquáticos. Contudo, estudos sobre a atividade de plantas moluscicidas em moluscos terrestres são pouco comuns, apesar de sua grande importância parasitológica e agrícola. As semelhanças anatomo-fisiológicas entre espécies de moluscos aquáticos e terrestres sugerem que estratégias de controle químico possam ter eficiência semelhante para os dois grupos de invertebrados. Com base nessa hipótese, o presente trabalho teve como objetivo avaliar a atividade moluscicida do látex de três espécies do gênero Euphorbia sobre Leptinaria unilamellata d'Orbigny, 1835, gastrópode terrestre descrito como hospedeiro intermediário de helmintos trematódeos digenéticos que parasitam animais domésticos. Destas E. milii var. splendens apresentou efeito moluscicida elevado sobre L. unilamellata, 100 por cento até uma diluição de 1:800, já nos primeiros minutos após a aplicação. Embora citadas na literatura como tóxicas para moluscos aquáticos, E. cotinifolia e E. tirucalli não exibiram atividade moluscicida sobre L. unilamellata. Os resultados do presente estudo indicam que o látex de E. milii var. splendens pode se constituir em uma estratégia viável de controle químico de moluscos terrestres.

Pulmonate terrestrial gastropods can be intermediate hosts for helminthes. The first records of chemically controlling these invertebrates date back to the beginning of the 20th century. The substances used were unspecific toxins which were already used for controlling other pests. Synthetic molluscicides have technical limitations that stimulated a search for natural substitutes. Among the many vegetal species that have molluscicidal activity, Euphorbia cotinifolia L., Euphorbia milii des Moul. var. splendens (Bojer ex Hook) Ursch & Leandri and Euphorbia tirucalli L. call attention because of the excellent results that have been obtained when they are used on aquatic mollusks. However, studies on the activity of molluscicidal plants on terrestrial mollusks are rare, in spite of its great importance in controlling parasites and to agriculture. Anatomical and physiological similarities among species of aquatic and terrestrial mollusks suggest that chemical control strategies can be effective on both groups of invertebrates. Based on this hypothesis, we assessed the molluscicidal activity of the latex of three species of the genus Euphorbia on the terrestrial gastropod Leptinaria unilamellata d'Orbigny, 1835, described as an intermediate host of digenetic trematode helminths that parasitize domestic animals. E. milii var. splendens had the highest molluscicidal effect on L. unilamellata, being 100 percent lethal in concentrations up to 1:1800 in the first minutes after application. Although E. cotinifolia and E. tirucalli have been cited in the literature as toxic to aquatic mollusks, they did not have molluscicidal activity on L. unilamellata. The results of our study indicate that the latex of E. milii var. splendens may be a viable strategy for the chemical control of terrestrial mollusks.

Intoxicação por Cnidoscolus phyllacanthus (Euphorbiaceae) em caprinos / Poisoning by Cnidoscolus phyllacanthus (Euphorbiaceae) in goats

Cnidoscolus phyllacanthus (Euphorbiaceae), com nome popular de favela, é uma planta normalmente espinhosa comum na caatinga. É considerada como forrageira e os animais, principalmente durante a seca, consomem as folhas que estão ao seu alcance ou as folhas secas caídas. A intoxicação espontânea por esta planta é relatada por fazendeiros no semi-árido quando animais têm acesso a plantas ou ramos recentemente cortados. Diferentes partes da planta moídas e secas, diluídas em água, são utilizadas por caçadores para matar pássaros. Para determinar a toxicidade de C. phyllacanthus, folhas verdes de plantas sem espinhos foram administradas a uma cabra em pequenas quantidades por via oral. Após o consumo de 4,7g por kg de peso do animal (g/kg) a cabra apresentou taquicardia, taquipneia, dispnéia, nistagmo, opistótono e decúbito esterno abdominal seguido de decúbito lateral. A morte ocorreu 30 minutos após o começo dos sinais. Folhas frescas de plantas sem espinho foram administradas a 8 caprinos em doses de 0,5-2,5g/kg sem que causassem sinais clínicos. Três animais apresentaram sinais clínicos após a ingestão de 3g/kg. Os sinais clínicos foram similares aos observados na intoxicação por ácido cianídrico e dois animais tratados com uma solução de tiossulfato de sódio a 20 por cento, na dose de 0,5ml/kg se recuperaram rapidamente em seguida ao tratamento. O terceiro recuperou-se espontaneamente. Folhas das mesmas plantas foram secadas ao sol durante períodos varáveis de 8-30 dias. O caprino que ingeriu a planta que tinha sido secada por 8 dias morreu após a ingestão de 3g/kg. O caprino que ingeriu a planta secada por 9 dias apresentou sinais clínicos após a ingestão de 1,13g/kg e se recuperou. Os caprinos que ingeriram a planta exposta ao sol por 10-29 dias apresentaram sinais clínicos após a ingestão de 3g/kg e se recuperaram espontaneamente ou mediante tratamento com tiossulfato de sódio. O caprino que ingeriu a planta que tinha sido exposta...

Cnidoscolus phyllacanthus (Euphorbiaceae), with the common name favela, is a generally spiny plant of the Brazilian semiarid. Mainly during the dry season livestock browse its leaves from the shrubs or ingest the dry leaves fallen to the ground. Farmers report the spontaneous poisoning by this plant when livestock has access to shrubs or branches that had been cut. Different parts of the ground fresh plant, diluted in water, are used by people in the semiarid to hunt birds. To determine the toxicity of C. phyllacanthus, leaves of the non-spiny plant were fed by hand to a goat by putting small amount into its mouth. After the consumption of 4.7g/kg body weight, the goat had tachycardia, tachypnoea, dyspnoea, nystagmus, opisthotonos and sternal recumbence. The death occurred 30 minutes after the onset of clinical signs. Fresh leaves from the same plants were given to 8 goats at doses of 0.5-2.5g/kg without causing clinical signs. Three goats showed clinical signs after the ingestion of 3g/kg. Clinical signs were similar to those observed in cyanide poisoning. Two goats given 0.5mg/kg of a 20 percent solution of sodium thiosulphate recovered immediately after treatment. Another goat recovered spontaneously. Leaves from the same plants were sun-dried during variable periods for 8-30 days, and then given to 8 goats. The goat that ingested the plant dried at the sun during 8 days died after the ingestion of 3 g/kg. The goat that ingested the plant, exposed to the sun for 9 days, showed clinical signs after the ingestion of 1.13g/kg, but recovered spontaneously. The goats that ingested the leaves exposed to the sun during 10-29 days showed clinical signs after the ingestion of 3g/kg, but recovered spontaneously or after treatment with sodium thiosulphate. No clinical signs were observed in the goat that ingested the plant that had been exposed to the sun during 30 days. In another experiment ground leaves of the plant were dried at the sun for...

Apoptosis and necrosis are involved in the toxicity of Sauropus androgynus in an in vitro study.

BACKGROUND/PURPOSE: The raw juice of the young sticks and leaves of Sauropus androgynus (SA) has been widely used as a natural food for body weight reduction and vision protection in Taiwan and Southeast Asia. But as has been reported, SA-associated obliterative bronchiolitis can develop after taking SA for more than 3 months. Lung transplantation was carried out in severe cases. METHODS: To study the toxic effect, we separated the SA extract into three parts, namely CHCl3, EtOAc and n-BuOH fractions, using polarity dissection. NIH3T3 fibroblasts were treated with the SA fractions 300 microg/mL and subjected to a series of cytotoxic assays. RESULTS: The EtOAc fraction exhibited the strongest effect of cell growth inhibition, followed by the CHCl3 and n-BuOH fractions. Features of condensed chromatin and apoptosis were observed in cells exposed to n-BuOH and EtOAc fractions using fluorescence microscopy. Formation of DNA ladders was also observed in the above cells. Instead, the CHCl3 fraction induced DNA smearing. In bivariate dot plots of annexin V and propidium iodide double staining, necrosis and apoptosis appeared in cells treated with CHCl3 and n-BuOH fractions, respectively, and a mixed type of necrosis and apoptosis appeared in EtOAc fraction-treated cells. CONCLUSION: Our results indicate that necrosis and apoptosis are involved in the toxic effect of SA in NIH3T3 fibroblasts. More evidence is needed to clarify if necrosis and apoptosis are also related to the pathogenesis of SA-associated obliterative bronchiolitis.

Evaluación de la acción citotóxica y embriotóxica del extracto metanólico de Alchornea castaneifolia "HIPORURO" / Evaluation of the cytotoxic and embryotoxic actions methanolic extract of Alchornea castaneifolia

Alchornea castaneifolia (Will) Jussieu es una planta medicinal perteneciente a la familia Euforbiáceae, conocida con numerosos nombres populares y múltiples usos en la Medicina Tradicional. En el presente trabajo, se evaluó la acción citotóxica del extracto metanólico al 10 por ciento p/v, en modelos del CYTED, siguiendo la técnica de De la Torre y la evaluación de la acción embriotóxica por la técnica de Gustafson y Estus. Observamos un retardo en el desarrollo del ciclo celular de Allium cepa y un retardo del desarrollo embrionario del erizo de mar, a nivel de blástula y gástrula, así como un aumento significativo de la mortalidad. En el análisis fitoquímico, de acuerdo a la Metodología de Ciulei, se pudo observar la presencia de: alcaloides, esteroides, triterpenos, azúcares reductores, saponinas, fenoles, taninos, quinonas, flavonoides, antocianidinas y principios amargos.

Alchomea castaneifoUa (WiU) Jussieu is a medicinal plant of the Euforbiaceae family, known for its many popular names and use in Traditional Medicine. We evaluated the cytotoxic and embryotoxic action of the methanolic extract at 10% w/v on Allium cepa L cells and on sea urchin embryos, using CYTED models. We found cytotoxic action supported by the marked delay of cell cycle in Allium cepa. The embryotoxic action consisted mainly of blastula and gastrula-arrested embryos and a statistically increased mortality. Phytochemical analysis was made using the Ciulei's method where alkaloids, steroids, phenols, saponines, flavonoids, quinines, antocyanidins and bitter principIes were found.

Evaluación de la toxicidad aguda y la acción hipolipemiante del aceite de Plukenetia volúbilis, Sacha Inchi / Evaluation of acute toxicity and hypolipemic action of Plukenetia volúbilis, Sacha Inchi

Se evaluó el efecto tóxico agudo del aceite de Plukenetia volúbilis (Sacha Inchi), determinando la Dosis Letal -50 (DL50) en 42 ratones de la cepa Nish, distribuidos en siete grupos de seis ratones cada uno, a los cuales se les administró, vía oral, dosis crecientes del aceite. Para evaluar el efecto hipolipemiante utilizamos 55 ratas albinas machos de la raza Holtzman, con un peso entre 194 g y 290 g y dos meses de edad. Se utilizó una dieta con 15 por ciento de grasas saturadas para elevar los lípidos séricos durante todo el tiempo del experimento. Utilizamos tres dosis diferentes de aceite de Sacha Inti, administradas durante 14 días consecutivos, comparando sus efectos con un control positivo (Lovastatina) y un control negativo (SF). Se controló el peso de los animales y los valores de colesterol, HDL y triglicéridos sanguíneos en tres tiempos diferentes. El análisis estadístico se realizó mediante el programa STATA 8.2. La DL50 fue de 111,65 mg/kg; hubo una reducción significativa de los valores sanguíneos de triglicéridos y LDL, mas no de colesterol y peso de los animales.

The acute toxic of Plukenetia volúbilis (Sacha Inchi) oil was evaluated. We calculated the Medial Lethal Dose (DL50) on 42 mice of the Nish strain, distributed in seven groups of six mice each, to whom a different and increasing dose was administered by oral route. To determine the hypolipidemic effect, we used 55 male albino rats of the Holtzman breed, whose weight fluctuateed between 194 and 290 g. The animals were fed with 15% of a saturateed fat diet for 14 days to produce hyperlipidemia during the whole period of the experiment. Treatment with Sacha Inchi oil in three different doses during 14 consecutive days was compared to the effects of a positive (lovastatine) and a negative control (physiological serum). The weight, cholesterol, HDL, LDL, VLDL, and triglycerides, were controlled in three different periods of time. Statistics analysis was made using the STATA 8.2 program. The DL50 was detrmined at 111,65 mg/Kg and the level of tryclicerides and LDL were statistically reduced, but not the cholesterol values or the animals' weight.

Investigation of the antimutagenic effects of selected South African medicinal plant extracts.

Dichloromethane extracts from different parts of Rhamnus prinoides, Ornithogalum longibracteatum, Gardenia volkensii, Spirostachys africana, Diospyros whyteana, Syzigium cordatum and Prunus africana were investigated for mutagenic and antimutagenic effects in Salmonella/microsome and micronucleus tests. None of the extracts tested in the Ames test were found to induce mutations or to modify the effect of the mutagen 4-nitroquinoline-oxide (4NQO). In the micronucleus test, extracts from twigs/bark of R. prinoides, twigs of D. whyteana, P. africana and S. cordatum significantly lowered the effect of the mutagen mitomycin C (MMC). Extracts from twigs/bark of G. volkensii and S. africana were genotoxic in the micronucleus test, while extracts of O. longibracteatum leaves potentiated the genotoxicity of MMC. This preliminary investigation shows that plant extracts used in traditional medicine may have particular effects with regard to mutagenicity and antimutagenicity indicating careful use in some instances and the need to isolate their active principles for further research.

Piscicidal effect of some common plants of India commonly used in freshwater bodies against target animals.

Mortality caused by the aqueous extracts of leaf and stem bark of four plants belonging to family Euphorbiaceae and Apocynaceae against freshwater fish Channa punctatus has been reported. It was found that dilute aqueous solutions of leaf and stem bark were active in killing the fishes. The toxic effect of stem bark of all the plants were time as well as dose dependent. There was significant negative correlation between LC50 and exposure periods. Thus, the LC50 values of stem bark extracts of Euphorbia royleana, Jatropha gossypifolia, Nerium indicum and Thevelia peruviana were decreased from 0.050 g/l (24 h) > to 0.020 g/l (96 h); 4.61 g/l (24 h) > to 4.34 g/l (96 h); 0.097 g/l (24 h) > to 0.041 g/l (96 h) and 4.05 g/l (24 h) > to 3.17 g/l (96 h), respectively. It has been suggested that these plant products cannot be used directly in freshwater bodies, without their detailed studies on long-term effects on non-target organism as well their structure activity relationship.

Laboratory evaluation of the molluscicidal properties of some Saudi Arabian euphorbiales against Biomphalaria pfeifferi.

Laboratory studies were conducted to evaluate the molluscicidal properties of three Saudi Arabian Euphorbiales. The results showed that the methanol extract of Euphorbia schimperiana has a high molluscicidal potency. The activity remains stable over a wide range of temperature and pH values, in the presence of organic and inorganic substrates and after exposure of the solutions to ultraviolet radiation.

Cytogenetic toxicity of leaf extract of Putranjiva roxburghii, a medicinal plant.

Young weaning Swiss albino mice were orally administered leaf extract of Putranjiva roxburghii at 0.5, 1.0 or 2.0 g/kg body weight/day for seven consecutive days. The results showed that the leaf extract significantly induced mitosis-disruptive chromosomal changes in bone marrow cells. No change in the incidence of structural abnormalities was, however, noticed among the metaphase chromosomes. It is proposed that the extract might have interfered with the spindle and other proteins causing polyploidy, aneuploidy, c-mitosis, etc.

The influence of environmental factors on the molluscicidal activity of Euphorbia milii latex.

The present study was undertaken to investigate the influence of biotic (snail size and presence of food during the test) and abiotic factors (temperature, water hardness and concentration of organic materials) on the molluscicidal activity of Euphorbia milii latex. Bioassays were conducted with B. glabrata (10 snails per concentration) and snail lethality was evaluated after 24 hr and 48 hr of exposure to lyophilized latex solutions. Neither the degree of water hardness, nor the presence of food during the test affected latex-induced snail mortality. The snail size had a minor influence on E. milii-induced snail lethality. Newly-hatched (shell diameter < or = 1 mm) as well as young (3-8 mm) snails were slightly less susceptible than older (10-25 mm) mollusks. On the other hand, the molluscicidal effect of E. milii latex was modified by environmental factors such as temperature (i.e., LC50 and LC90 values were halved for every 10 degrees C rise in temperature) and concentration of organic materials in the water (i.e. the higher the concentration of organic matter, the higher the LC50 value). The efficacy of E. milii latex as a molluscicide can be modified by factors such as water temperature and concentration of organic materials, and to a lesser extent by snail size.

Effects of an essential oil from the bark of Croton cajucara Benth. on experimental gastric ulcer models in rats and mice.

Croton cajucara Benth. (Euphorbiaceae) is widely used in Amazonian folk medicine for the treatment of a wide range of gastrointestinal symptoms. The essential oil from its bark was investigated for acute toxicity in mice and for its ability to prevent the formation of ulceration of the gastric mucosa in different models of experimentally induced gastric ulcer in mice and rats. When previously administered orally at a dose of 100 mg kg(-1), the essential oil significantly reduced (P < 0.01) the gastric injury induced by hypothermic restraint stress (48%), indomethacin (47%), ethanol (86%) and pylorus ligature models (87%) in rats. In the HCl/ethanol-induced gastric ulcer model in mice, at oral doses of 100 and 200 mg kg(-1), the essential oil from C. cajucara significantly reduced (P < 0.01) the formation of gastric lesions by 52% and 67%, respectively, when compared with the control group. In rats submitted to pylorus ligature, the essential oil given orally increased the volume of gastric juice when compared with the control group (P < 0.01). When the essential oil (100 mg kg(-1)) was administered intraduodenally to mice, significant modifications were found in gastric parameters such as pH and total acid content after oil treatment. We observed significant changes (P < 0.01) in gastric juice parameters such as an increase in volume and a decrease in gastric acidity (pH and total acid content). The acute toxicologic effects of the essential oil from C. cajucara were assessed in mice. The LD50 values were 9.3 g kg(-1) by the oral route and 680 mg kg(-1) by the intraperitoneal route. The good yield of essential oil obtained from dried C. cajucara bark (1%) as well as its anti-ulcerogenic activity and low toxicity suggest that pharmacological studies of this substance as a potential new anti-ulcerogenic drug are warranted.