Low cytotoxicity, and antiproliferative activity on cancer cells, of the plant Senna alata (Fabaceae) / Baja citotoxicidad, y actividad antiproliferativa sobre las células cancerosas, de la planta Senna alata (Fabaceae)

Introduction: The leaves of Senna alata from the Fabaceae family have been used in folk medicine for the cure of skin disease. In this study, we tested the extract and fractions on brine shrimp lethality test and antiproliferative activity on cancer and normal cell lines. Objective: In this study, we assessed the cytotoxicity of S. alata using brine shrimp test and two cell lines. Methods: The 80 % ethanolic leaf extract and its fractions were examined for possible cytotoxic effect using sulforhodamine B (SRB) cytotoxicity assay towards breast cancer (MCF-7), normal (MCF10A) cell lines, and brine shrimp lethality test (BSLT). Results: The brine shrimp lethality bioassay exhibits no cytotoxicity even at high concentration (5 000 µg/mL). The LC50 for dichloromethane, chloroform, butanol, and aqueous were > 1 000 µg/mL (non-toxic). The IC50 for in vitro SRB cytotoxicity against MCF-7 for n-hexane was 0.013 µg/mL, which was considered highly toxic, while dichloromethane and chloroform recorded at 47.11 and 57.61 µg/mL, respectively after 72 hours exposure time although there was no cytotoxicity found on the normal cell line. Conclusion: This study shows that S. alata crude ethanolic leaf extract and its fractions potentially contain significant bioactive compounds that are safe from adverse effects, which proves the therapeutic application of S. alata in traditional remedy.

Introducción: Las hojas de Senna alata de la familia Fabaceae se han utilizado en la medicina popular para la cura de enfermedades de la piel. En este estudio, probamos el extracto de la planta en líneas celulares normales y cancerosas. Objetivo: Evaluamos la citotoxicidad de S. alata usando una prueba del camarón Artemia y la actividad antiproliferativa. Métodos: El extracto de hoja etanólico al 80 % y sus fracciones se examinaron en busca de un posible efecto citotóxico utilizando un ensayo de citotoxicidad de sulforrodamina B (SRB) frente a líneas celulares de cáncer de mama (MCF-7), normales (MCF10A) y prueba de letalidad del camarón Artemia (BSLT). Resultados: El bioensayo de letalidad del camarón Artemia no presenta citotoxicidad incluso en alta concentración (5 000 µg/mL). La CL50 para diclorometano, cloroformo, butanol y acuoso fue > 1000 µg/mL (no tóxico). La CI50 para la citotoxicidad in vitro de SRB contra MCF-7 para n-hexano fue de 0.013 µg/mL, que se consideró altamente tóxica, mientras que el diclorometano y el cloroformo registraron 47.11 y 57.61 µg/mL, respectivamente, después de 72 horas de tiempo de exposición, aunque no hubo citotoxicidad encontrada en la línea celular normal. Conclusión: Este estudio muestra que el extracto de hoja etanólico crudo de S. alata y sus fracciones contienen potencialmente compuestos bioactivos significativos que están a salvo de efectos adversos, lo que demuestra la aplicación terapéutica de S. alata como remedio tradicional.

Poisoning by Senna obtusifolia in sheep / Intoxicação por Senna obtusifolia em ovinos

In a paddock highly invaded by Senna obtusifolia 10 out of 60 sheep showed muscle weakness and 9 died after a clinical manifestation period of 24-76 hours. Serum activities of creatine kinase were increased in all sheep examined. Multifocal polyphasic muscle segmental degeneration and necrosis was observed in skeletal muscles. Although the plant is a common weed in northeastern Brazil, the poisoning is rare, probably because the animals do not ingest it or due to toxicity variations.(AU)

Em um piquete altamente invadido por Senna obtusifolia, 10 de 60 ovelhas mostraram fraqueza muscular e 9 morreram após um período de manifestação clínica de 24-76 horas. As atividades séricas da creatina quinase foram aumentadas em todos os ovinos examinados. Foi observada degeneração segmentar e necrose polifásica muscular em músculos esqueléticos. Embora a planta seja uma erva daninha comum no Nordeste do Brasil, o envenenamento é raro, provavelmente porque os animais não o ingerem ou devido a variações de toxicidade.(AU)

Anti-nociceptive effect of methanol extract of leaves of Senna singueana in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Senna singueana (Del.) Lock (Fabaceae) is a shrub or tree found in Ethiopia and other African countries. It has been traditionally used for different conditions including treatment of pain conditions in humans and animals. Although various reports are available in the literature claiming different activities of the plant, scientific studies supporting analgesic potential of S. singueana are lacking and the present study aimed to investigate the antinociceptive effect of methanol extract of leaves of S. singueana in mice. MATERIALS AND METHODS: Anti-nociceptive activity of S. singueana (200 mg/kg and 400 mg/kg, p.o) was investigated using acetic acid-induced writhing, formalin-induced paw licking, and hot plate tests. Acute oral toxicity was determined using a slightly modified guideline (423) of the Organization for Economic Cooperation and Development. RESULTS: S. singueana extract increased the percentage of inhibition of writhing response and licking response (neurogenic and inflammatory phase) in acetic acid-induced writhing and formalin-induced paw licking tests, respectively. It also significantly (p ≤ 0.05) increased the percentage of mean maximal effect (%MPE) compared to control group in the hot-plate test. In all models, the combination of S. singueana with either diclofenac or morphine produced statistically significant increase (p ≤ 0.05) in the percentage of inhibition of writhing, paw licking, and %MPE compared to single treatment groups. It was also found that the 400 mg/kg extract produced higher antinociceptive effects (p ≤ 0.05) compared to the 200 mg/kg. CONCLUSION: S. singueana leaves may have analgesic effect that is mediated through both peripheral and central mechanisms and could be used as adjuvant treatment to the modern analgesics.

Toxicity of Senna occidentalis seeds in laying hens and its effects on egg production.

Senna occidentalis is a toxic leguminous plant found in many tropical and subtropical regions of the world and causes poisoning mainly in confined animals. The seeds are the most toxic part of the plant and may be present in animal rations. The main toxic component of the S. occidentalis seed is a dianthrone, an anthraquinone-derived compound that affects mitochondrial function. This study evaluated the effects on egg production of low-level contamination of the S. occidentalis in the laying hens' diet. Forty-eight one-day-old pullets were randomly allocated into two treatment groups: control, birds that received no experimental treatment; and external and internal tegument (ET/IT), birds that received a diet containing 0.2% of ET/IT of S. occidentalis seeds throughout their life cycle (42 weeks). The birds were monitored for clinical signs of poisoning, and the production and quality of eggs were recorded. Necropsies were conducted at the end of the experimental period. None of the layers showed any clinical signs of poisoning, decreases in feed intake or alterations of the body weight gain. A marked reduction in egg production and, consequently, a lower feed efficiency in ET/IT group were measured. Ovaries were the most affected organ in birds from the ET/IT group, and yolk leaking and dysplasia of the inner layer of the vitelline membrane were observed. S. occidentalis was shown to be toxic for laying hens. Considering these results, it is feasible to assume that the constant presence of low concentrations of S. occidentalis seeds in rations represents a threat to the poultry industry.

Effects of long-term administration of Senna occidentalis seeds on the hematopoietic tissue of rats.

Senna occidentalis (S. occidentalis) is a toxic leguminous plant that contaminates crops and has been shown to be toxic to several animal species. All parts of the plant are toxic, but most of the plant's toxicity is due to its seeds. Despite its toxicity, S. occidentalis is widely used for therapeutic purposes in humans. The aim of the present work was to investigate, for the first time, the effects of the chronic administration of S. occidentalis seeds on hematopoietic organs, including the bone marrow and spleen. Fifty male Wistar rats were divided into five groups of 10 animals. Rats were treated with diets containing 0% (control), 0.5% (So0.5), 1% (So1), or 2% (So2) S. occidentalis seeds for a period of 90 days. Food and water were provided ad libitum, except to pair-fed (PF) group which received the same amount of ration to those of So2 group, however free of S. occidentalis seeds. It was verified that rats treated with 2% S. occidentalis seeds presented changes in hematological parameters. The blood evaluation also showed a significant decrease of the Myeloid/Erythroid (M/E) ratio. Chronic treatment with S. occidentalis promoted a reduction in the cellularity of both the bone marrow and spleen. Additionally, we observed changes in bone marrow smears, iron stores and spleen hemosiderin accumulation. Histological analyses of bone marrow revealed erythroid hyperplasia which was consistent with the increased reticulocyte count. These findings suggest that the long-term administration of S. occidentalis seeds can promote blood toxicity.

Activity-guided chemo toxic profiling of Cassia occidentalis (CO) seeds: detection of toxic compounds in body fluids of CO-exposed patients and experimental rats.

Our prior studies have shown an association between the deaths of children and consumption of Cassia occidentalis (CO) seeds. However, the chemicals responsible for the CO poisoning are not known. Therefore, the present study was designed to identify the key moieties in CO seeds and their cytotoxicity in rat primary hepatocytes and HepG2 cells. Activity-guided sequential extraction and fractionation of the seeds followed by GC-MS analysis identified the toxic compounds in the CO seeds. These identified compounds were subsequently detected and quantified in blood and urine samples from CO-exposed rats and CO poisoning human study cases. GC-MS analysis of different fractions of methanol extracts of CO seeds revealed the presence of five anthraquinones (AQs), viz. physcion, emodin, rhein, aloe-emodin, and chrysophanol. Interestingly, these AQs were detected in serum and urine samples from the study cases and CO-exposed rats. Cytotoxicity analysis of the above AQs in rat primary hepatocytes and HepG2 cells revealed that rhein is the most toxic moiety, followed by emodin, aloe-emodin, physcion, and chrysophanol. These studies indicate that AQ aglycones are responsible for producing toxicity, which may be associated with symptoms of hepatomyoencephalopathy in CO poisoning cases.

Toxic myopathy and acute hepatic necrosis in cattle caused by ingestion of Senna obtusifolia (sicklepod; coffee senna) in Brazil.

The epidemiological, clinical and pathological findings of field and experimental Senna obtusifolia (sicklepod; coffee senna) poisoning in cattle are described. The low availability of good quality forage and high rate of infestation of pastures by S. obtusifolia were the factors that led to poisonous plant ingestion. In this study, the morbidity ranged between 2% and 27.9%, and the lethality was 100%. For the experimental study, six cattle were fed with the aerial parts of S. obtusifolia collected in three different seasons at 9%-38% of the animal's body weight. The experimental and field diseases were similar. The main clinical signs were diarrhea, reluctance to move, muscular weakness and recumbency. The gross findings included pale discoloration of the skeletal muscle. Microscopically, the affected cattle showed degeneration and necrosis of the skeletal muscles and occasionally of the cardiac muscles. Additionally, two cattle showed centrilobular hepatic necrosis. In this study, S. obtusifolia collected from the same farm showed seasonal variation in toxicity. Poisoning by S. obtusifolia is an important cause of death of cattle in the Central Western region of Brazil. The toxicosis caused by this plant is similar to S. occidentalis poisoning; however, in S. obtusifolia poisoning, acute hepatic necrosis is sometimes present.

Toxicology study of senna (CAS No. 8013-11-4) in C57BL/6NTAC Mice and toxicology and carcinogenesis study of senna in genetically modified C3B6.129F1/Tac-Trp53tm1Brd haploinsufficient mice (Feed Studies).

Senna is used as a stimulant laxative in the management of constipation resulting from opioid use or when treatment with bulking or osmotic agents has failed. Increased use of senna was expected due to the removal of the stimulant laxatives danthron and phenolphthalein from the market. Senna was nominated for study by the Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA) due to the wide use of laxative preparations, positive genotoxicity in vitro for some senna components or metabolites, and unknown carcinogenic potential. Because a 2-year rat study was ongoing by the manufacturer, the FDA requested that the NTP conduct a senna study in the p53(+/-) mouse. In this study, the potential for carcinogenic effects of senna was studied in the C3B6.129F1/Tac-Trp53tm1Brd N12 haploinsufficient (heterozygous F1 p53(+/-)) mouse model as an ongoing goal of the NTP to develop and test model systems for toxicology and carcinogenesis studies, especially those that can provide mechanistic information relative to understanding an agents mode of action. C57BL/6NTac mice were exposed to senna in feed for 5 weeks; heterozygous F1 p53(+/-) mice were exposed to senna in feed for 40 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes.

Intoxication by Senna occidentalis seeds in pregnant goats: prenatal and postnatal evaluation.

Senna occidentalis is a weed toxic to different animal species. Very little is known about the effects of prolonged exposure to low doses of S. occidentalis on developmental toxicology. Thus, the present study proposes an approach to evaluate the perinatal toxicity of S. occidentalis seeds in goats. Twenty-one pregnant goats were fed rations containing 0% (control), 1% (So1 group), 2% (So2 group) and 4% (So4 group) mature S. occidentalis seeds from pregnancy detection on day 27 after mating until parturition; weight gains and serum biochemistry were evaluated. Fetuses were evaluated using ultrasonographic measurements; neonates were evaluated by body morphometry, weight gains, and serum biochemistry. Fetal resorption occurred in 2 So4 dams and one dam died. Only a few minor alterations in serum biochemistry occurred in dams and kids; even so one So4 group dam had tissue lesions as vacuolations in hepatocytes and kidneys; necrosis in skeletal and cardiac muscles and for the first time lesions were observed in sciatic nerve cells. No relevant alterations in body morphometry were observed. This study suggests that 4% S. occidentalis seeds is toxic for pregnant goats, but levels of seeds less than 4% have little impact on fetal and post birth body development.

Cassia occidentalis L.: a review on its ethnobotany, phytochemical and pharmacological profile.

Cassia occidentalis L. is an annual or perennial Ayurvedic plant which is used in several traditional medicines to cure various diseases. This weed has been known to possess antibacterial, antifungal, antidiabetic, anti-inflammatory, anticancerous, antimutagenic and hepatoprotective activity. A wide range of chemical compounds including achrosin, aloe-emodin, emodin, anthraquinones, anthrones, apigenin, aurantiobtusin, campesterol, cassiollin, chryso-obtusin, chrysophanic acid, chrysarobin, chrysophanol, chrysoeriol etc. have been isolated from this plant. The presented review summarizes the information concerning the botany, ethnopharmacologyquery, phytochemistry, biological activity and toxicity of the C.occidentalis plant.

Revisión de la literatura sobre la toxicidad del sen / No disponible

El objetivo de este artículo es revisar la información de la literatura científica sobre la toxicidad de la hoja y el fruto de sen. Este análisis establece que: -No existen evidencias suficientes de que el uso crónico de sen tenga como consecuencia una alteración estructural y/o funcional de los nervios entéricos o del músculo liso intestinal. -No existe relación entre la administración a largo plazo de un extracto de sen y aparición de tumor es gastrointestinales o de otra índole en la rata. -El sen no es carcinogénico en ratas incluso después de una administración diaria durante dos años en dosis de hasta 300 mg/kg/día. -La evidencia de que se dispone en la actualidad no demuestra que exista un riesgo de genotoxicidad para los pacientes que consumen laxantes que contienen extractos de sen o senósidos (AU)

The aim of this article is to review the scientific literature about the toxicity of senna leaves and senna pods. This analysis stablish that: - There are not definitive evidences about the effects of the chronic uses of senna on the structural or functional alteration on the enteric nerves or on intestinal smooth muscle. -There is no relation between the long term administration of senna and gastrointestinal or another tumours in rats. - Senna is not carcinogenic on rats even after the daily administration, during two years, at doses of at least 300 mg/kg/day. -Nowadays, the evidences do not confirm the genotoxicity risk on patients consuming laxatives containing senna or sennosides (AU)

Effect of Senna occidentalis seeds on immunity in broiler chickens.

This study investigated possible immunotoxic effects of Senna occidentalis (So) seeds incorporated in broiler chicken rations at different concentrations (0.0%, 0.25%, 0.50% and 0.75%), for 28 or 42 days. We evaluated innate immune function (macrophage activities of spreading, phagocytosis, peroxide and nitric oxide production) and acquired immune function (humoral and cellular immune responses), as well as lymphoid organ weights and pathology. There was enhanced macrophage activity, as hydrogen peroxide production increased (P < 0.05) in cells of birds given 0.75%So, but there were no other pro-inflammatory effects. Birds receiving 0.75% of So in ration for 42 days gained less weight (P < 0.01), and showed a decrease in relative weight of the bursa of Fabricius (P < 0.05) and spleen (P < 0.01). In addition, morphological changes were also noted in these lymphoid organs, with depletion of lymphoid cells on the spleen and bursa of Fabricius, resulting in lower relative weight of both lymphoid organs. No impairment of humoral immune response against Newcastle disease and in cellular immune response after a phytohaemagglutinin challenge was found. It is probable that mitochondrial damage and related apoptosis may be responsible for the enhanced peroxide production and the reduced relative weight of the bursa of Fabricius and spleen.

Sub-acute intoxication by Senna occidentalis seeds in rats.

Senna occidentalis (So) is a weed that grows in pastures along fences and in fields cultivated with cereals such as corn and soybean, and many reports have been showing intoxication with this plant in different animal species. It is also used in many medicinal purposes. The objective of the present study was to better evaluate the toxic effects of prolonged administration of So seeds to rats. Forty male Wistar rats were divided into four groups of 10 animals each, three of them respectively fed rations containing 1%, 2% and 4% So seeds, and the last one (control) fed commercial ration for a period of 2 weeks. Fourteen rats were also used in a pair-feeding (PF) experiment. The rats of the experimental groups showed lethargy, weakness, recumbency, depression and emaciation. Two rats of the 4% group and two of the PF group died during the experiment. Histopathological study showed fiber degenerations in the skeletal (Tibial, pectoral and diaphragm) and cardiac muscles. In the liver parenchyma, was observed vacuolar degeneration and, in the kidney, mild nefrosis in the proximal convoluted tubules. All of these alterations occurred in a dose-dependent fashion. Moderate to severe degeneration and spongiosis in the central nervous system, especially in cerebellum. Electron microscopy revealed mitochondrial lesions in all analyzed tissues.

Effects of Senna occidentalis on chick bursa of Fabricius.

Senna occidentalis (L) Link (formerly called Cassia occidentalis) is a toxic leguminous plant found ubiquitously as a contaminant of crops. All parts of the plant are toxic, but most of the S. occidentalis toxicity is found in the seeds. S. occidentalis has been shown to be toxic to several animal species, causing degenerative lesions mainly in muscles. This is the first report describing alterations in chick lymphoid organs caused by S. occidentalis seeds. The objectives of this study were to describe the effects of the treatment with seeds and its fraction external tegument (TE) on the development of chicks and their lymphoid organs bursa of Fabricius and spleen. Chicks that received a commercial ration with 1% TE had reduced body and lymphoid organ weights. The bursa of Fabricius presented reduction in the diameters of the follicles, and in the thickness of the cortical and medullary regions. The spleen presented depleted lymphoid tissue in the white pulp. These results indicate that the active principle of S. occidentalis is more concentrated on its TE fraction, and that it can cause weight loss as well as alterations in the lymphoid organs in chicks. The consequences of these alterations should be further investigated.

Passiflora incarnata L. y Senna alata (L) Roxo: Estudio toxicogenético que emplea 2 sistemas de ensayo a corto plazo / Passiflora incarnata L and Senna alata (L) Roxo: A toxicogenetic study using 2 short-term test systems

Con el objetivo de conocer el posible efecto toxicogenético de los extractos fluidos de Passiflora incarnata L. (pasiflora) y Senna alata (L.) Roxo (guacamaya francesa), se llevó a cabo un estudio mutagénico empleando 2 sistemas de ensayo a corto plazo, uno in vitro y otro in vivo: el modelo Aspergillus nidulans D-30 que detecta daño primario al ADN y el ensayo de inducción de micronúcleos en médula ósea de ratón el cual determina daño clastogénico y aneugénico. En el ensayo in vitro con el hongo Aspergillus nidulans D-30 (segregación mitótica) se evaluaron concentraciones del extracto fluido de Passiflora incarnata L.; desde 0,162 a 1,296 mg de sólidos totales/mL y para la Senna alata (L.) Roxo, concentraciones de 0,504 a 2,912 mg de sólidos totales/mL. En la prueba in vivo de inducción de micronúcleos se ensayaron para la Passiflora incarnata L. y para la Senna alata (L.) Roxo dosis de 0,607; 1,215; 2, 430 y 1 313,00; 2 625,00; 5 250,00 mg/kg de peso corporal (pc), respectivamente. En ambas baterías de ensayos genotóxicos ninguno de los 2 fitofármacos mostró daño celular ni actividad mutagénica(AU)

Estudio fitofarmacológico de Senna spectabilis (D.C) I&B / Phytopharmacology study of Senna spectabilis (D.C.)I&B

Se realizó el estudio fitofarmacológico de Senna spectabilis. Se efectuó la extracción de los alcaloides de la corteza de la planta y se determinó su actividad farmacológica y su toxicidad. Se demostró un efecto anticoagulante de los alcaloides totales y se logró reproducir en el animal experimental las alteraciones hematológicas. Los alcaloides muestran un aumento de la actividad motriz espontánea, inferior a la producida por la anfetamina, pero notoria en la dosis de 25 mg/Kg. La administración de los alcaloides a los animales de experimentación produce, además, convulsiones. Se determinó en ratones la DL50 de los alcaloides totales, obteniéndose un resultado de 31 mg/Kg de peso. Se efectuó un estudio histopatológico de algunos órganos de las ratas y ratones utilizados en los ensayos de actividad farmacológica y se observaron daños ocasionados por la administración de los alcaloides totales