Developmental stages of zebrafish (Danio rerio) embryos and toxicological studies using foldscope microscope.

Zebrafish (Danio rerio), is a well-established vertebrate animal model widely used in developmental biology and toxicological research. In the present study, foldscope is used as an innovative tool to study the developmental stages and toxicological analysis of the zebrafish embryos. Briefly, the developmental stages, such as zygote, cleavage, blastula, gastrula, segmentation, and pharyngula formation are observed and documented using simple foldscope. Toxicological parameters upon exposure to different concentration of ethanol extract of Curcuma longa and its lead compound, ar-turmerone along with rhodamine B (bio-coupler) on zebrafish embryos are analyzed upto 72 hr using foldscopes in live condition. The lethal endpoints, such as coagulation, lack of somite formation, non-detachment of tail, and lack of heartbeat are clearly monitored and documented using foldscope. Bio-evaluation of test compounds with the aid of foldscope confirms that the toxicity is directly proportional to the concentration. Our results conclude that, ethanol extract of C. longa, ar-turmerone and rhodamine B exposed embryos remains healthy up to 96, 48, and 24 µg concentrations, respectively. Embryos exposed to higher concentrations become coagulated, however normal physiological active movement of tail lashing and heartbeat are evident in lower concentration exposed embryos. Except coagulation, no other abnormalities are observed and interestingly, the hatching ability is not delayed, when compared with the control embryos. It is confirmed that the test compounds are not highly toxic to zebrafish embryos. Hence it can be used for further analysis, especially for studying the neural-regeneration and its neuronal development in zebrafish embryos.

Toxicological safety evaluation of a novel highly bioavailable turmeric extract formulation.

Turmeric (Curcuma longa L.) extracts have a long history of use worldwide, but a major limitation of these extracts is their extremely low oral bioavailability, caused by low absorption, rapid metabolism and rapid excretion following ingestion. Thus, a new highly bioavailable turmeric extract formulation (comprising turmeric extract, acacia gum, sunflower oil and quillaia extract) has been developed and is intended for use as a food ingredient. Safety of this novel extract was evaluated using the standard Tier 1 battery of in vitro genotoxicity tests (bacterial reverse mutation test and an in vitro mammalian cell micronucleus test) followed by repeated-dose 28- and 90-day oral toxicity studies in rats. In the 90-day study, male and female Sprague-Dawley rats were dosed once daily, by oral gavage, either with the vehicle or the test item at 500, 1500 or 3000 mg/kg body weight/day. Clinical examinations were conducted regularly, and body weights and food consumption were recorded weekly throughout the study. At the end of the study, blood samples were analyzed for clinical pathology parameters, before a macroscopic necropsy was conducted and a full list of tissues were examined histopathologically. There was no evidence of genotoxicity in vitro. No test item-related adverse effects were observed in the 28- or 90-day studies; therefore, 3000 mg/kg body weight/day (the maximum feasible dose and highest dose tested in rats) was established as the no-observed-adverse-effect level.

Combination of aqueous extracts of Curcuma longa (turmeric) and some calcium channel blockers synergistically improves CCl4-induced nephrotoxicity in albino rats.

In the present study, special attention was drawn to CCl4-induced acute kidney injury (AKI) and how the nephrotoxicity could be treated or prevented by administration of aqueous extracts of Curcuma longa (AECL) alone or in combination with some calcium channel blockers. Thirty (30) male albino wister rats were grouped according to their weight into 6 groups (A-F) of 5 rats per group. Rats in groups A-D received CCl4 (0.4ml/kg b.wt, i.p) for 3 days. Group B received AECL (200mg/kg, oral), Group C received AECL and nifedipine (1mg/100g of rat, i.p), Group D received AECL and amlodipine (1mg/100g of rat, i.p), and group E received AECL alone with no CCl4 challenge for 3 days. No treatment was administered to group F (Normal control). Serum renal biochemical parameters; MDA level and SOD activity in the kidney homogenates were measured. CCl4 administration to the rats resulted to acute kidney injury with significantly increased Urea, Creatinine, K+ and MDA levels and decreased SOD activity (p<0.05, p<0.01 or p<0.001). The 3 days daily administration of AECL alone or plus nifedipine or amlodipine resulted in the attenuation of the CCl4-induced kidney injury with significantly decreased Urea, Creatinine, K+ and MDA levels and increased SOD activity (p<0.05. p<0.01). Histopathological results showed a concomitant association with the biochemical findings. This study shows that the combination of the extract and some calcium channel blockers is synergistically nephroprotective and can be used to prevent acute renal injury.

Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα.

Extracts from the rhizome of the turmeric plant are widely consumed as anti-inflammatory dietary supplements. Turmeric extract contains the three curcuminoids, curcumin (≈80% relative abundance), demethoxycurcumin (DMC; ≈15%), and bisdemethoxycurcumin (BDMC; ≈5%). A distinct feature of pure curcumin is its instability at physiological pH, resulting in rapid autoxidation to a bicyclopentadione within 10-15 min. Here, we describe oxidative transformation of turmeric extract, DMC, and BDMC and the identification of their oxidation products using LC-MS and NMR analyses. DMC autoxidized over the course of 24 h to the expected bicyclopentadione diastereomers. BDMC was resistant to autoxidation, and oxidative transformation required catalysis by horseradish peroxidase and H2O2 or potassium ferricyanide. The product of BDMC oxidation was a stable spiroepoxide that was equivalent to a reaction intermediate in the autoxidation of curcumin. The ability of DMC and BDMC to poison recombinant human topoisomerase IIα was significantly increased in the presence of potassium ferricyanide, indicating that oxidative transformation was required to achieve full DNA cleavage activity. DMC and BDMC are less prone to autoxidation than curcumin and contribute to the enhanced stability of turmeric extract at physiological pH. Their oxidative metabolites may contribute to the biological effects of turmeric extract.

The hazardous effects of three natural food dyes on developmental stages and longevity of Drosophila melanogaster.

Nowadays, food dyes obtained from herbal, animal, microbial and mineral sources are widely used as food additives. In this study, the toxic effects of three different natural food dyes (carmine, turmeric and annatto) on 72 ± 4 h larvae of Oregon-R wild type of Drosophila melanogaster were investigated. For this purpose, four different application doses (50, 75, 100, 125 mg mL(-1)) were chosen by means of preliminary studies. It was determined that larval mortality increased with increasing concentration in the application groups and the toxicity order was carmine > turmeric > annatto. It was observed that the survival rate was highest in the control with 98% and lowest in 125 mg mL(-1) carmine with 16%. In addition, the average lifespan of the adult individuals obtained from third instar larvae was also studied. While the average lifespan was 40.88 ± 1.44 days in the control group, these values were 10.81 ± 0.55-23.90 ± 1.27 days in the carmine group, 15.00 ± 0.80-22.42 ± 1.43 days in the turmeric group and 10.33 ± 1.03-35.68 ± 1.54 days in the annatto group, respectively. According to the obtained results, when both the developmental period from larvae into adults and the lifespan of the developing adults were compared with the control group, the food dyes were found to be toxic and the toxicity order of carmine > turmeric > annatto was identified.

Curcumin: an anti-inflammatory molecule from a curry spice on the path to cancer treatment.

Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer's disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.

Safety Evaluation of Standardized Extract of Curcuma longa (NR-INF-02): A 90-Day Subchronic Oral Toxicity Study in Rats.

NR-INF-02 is a standardized extract containing turmerosaccharides from Curcuma longa that has anti-inflammatory, analgesic, and chondroprotective potential. In view of its potential uses, NR-INF-02 was evaluated for its safety in Wistar rats at an oral dose of 250, 500, and 1000 mg/kg in a 90-day repeated dose subchronic toxicity study. NR-INF-02 administered at 250, 500, and 1000 mg/kg for 90 days did not show any mortality or clinical signs of toxicity. Body weight gain, food consumption, ocular and neurological examination, and hematological, blood biochemical, hormone, and urine analysis revealed no evidence of toxicity of NR-INF-02 treatment in rats. Absolute and relative organ weights were comparable to control rats. The study did not reveal any major treatment related gross pathological and histopathological alterations in the tissues or organs examined. Thus, based on study observations, the no-observed adverse effect level (NOAEL) was found to be 1000 mg/kg body weight in albino Wistar rats.

Efficacy and Safety Curcuma zadoaria L. to Inactivate the Hydatid Cyst Protoscoleces.

BACKGROUND: The present work aimed to evaluate the chemical composition of Curcuma zadoaria essential oil and to investigate its efficacy and safety against hydatid cyst protoscoleces. METHODS: Collected protoscoleces from liver fertile hydatid cysts of infected sheep were exposed to different concentrations of the essential oil (75, 150, 300 µl/mL) for 5-30 min in vitro and ex vivo. Then, by using the eosin exclusion assay, the viability of protoscoleces was studied. In the next step, 24 male NMRI mice were examined to assess the toxicity of C. zadoaria essential oil by measuring the biochemical and hematological parameters. RESULTS: Based on the obtained results, the LD50 value of intraperitoneal injection of the C. zadoaria essential oil was 1.76 mL/kg of body weight and the maximum non-fatal dose was 0.96 mL/kg of body weight. C. zadoaria essential oil had a strong proto scolicidal activity in vitro so that at the 300 and 150 µl/ml entirely eliminates the parasite after 5 and 10 minutes; whereas, weak proto scolicidal activity was observed at lower doses. Ex vivo assay, no similar effect with in vitro was observed, therefore, more time is required to show a potent proto scolicidal activity. C. zadoaria essential oil at the concentrations of 300 and 150 µl/mL after an exposure time of 7 and 12 min, killed 100% of protoscoleces within the hydatid cyst, respectively. After intraperitoneal injection of the C. zadoaria essential oil for 2 weeks, no significant difference (p > 0.05) was observed in the clinical chemistry and hematologic parameters at the doses of 0.15, 0.3, 0.6 mL/kg. CONCLUSION: The obtained results in vitro and ex vivo exhibited that C. zadoaria essential oil had a favorable proto scolicidal activity on hydatid cyst protoscoleces. However, more supplementary works are required to verify these findings by assessing clinical subjects.

Subfertility effects of turmeric (Curcuma longa) on reproductive performance of Pseudotropheus acei.

This study was conducted to determine the effect of turmeric powder dietary supplementation on the histology of visceral organs and reproductive performance of Pseudotropheus acei. The fish were fed dietary additions of 0%, 1%, 3%, 5%, and 7% turmeric powder. Each treatment was replicated three times. There were one male and four female fish with a mean weight of 6 g in each replicate. The fish were fed ad libitum for 90 days. There were no differences in fertility rate, fecundity rate, hatching rate, egg diameter, and larvae survival rate among groups (P < 0.05). Ovulation frequency and the percent of spawning broodstock were less in the 7% and 5% turmeric-supplemented group (P < 0.05), while there were no effects of treatment in the 1%, and 3% groups compared with the control group. Observations in histopathological examinations indicated there were normal tissue structures in the control, 1% and 3% turmeric-supplemented groups, while the addition of 5% and 7% turmeric induced a degeneration of and decrease in number of observable ovarian follicles. In addition, there was a normal liver structure in the control and the 1% and 3% turmeric-supplemented groups and slight to severe lipidosis in the 5% and 7% turmeric-supplemented groups. Also, the supplementation of larger amounts of turmeric induced enteritis and the slight to severe side effects on the relevant organs. These results indicate that supplementing of diets with turmeric powder in amounts of 5% and 7% suppressed ovarian follicle development, and extended periods between times of spawning which resulted in subfertility of broodstocks.

In vitro cytotoxicity of curcuminoids against head and neck cancer HNO97 cell line / Citotoxicidade in vitro de curcuminoides contra a linhagem de células HNO97 de câncer de cabeça e pescoço

Oral squamous cell carcinoma (OSCC) is a malignant tumour of Head and Neck Cancer (HNC). The recent therapeutic approaches used to treat cancer have adverse side effects. The natural agents exhibiting anticancer activities are generally considered to have a robust therapeutic potential. Curcuminoids, one of the major active compounds of the turmeric herb, are used as a therapeutic agent for several diseases including cancer. In this study, the cytotoxicity of curcuminoids was investigated against OSCC cell line HNO97. Our data showed that curcuminoids significantly inhibits the proliferation of HNO97 in a time and dose-dependent manner (IC50=35 μM). Cell cycle analysis demonstrated that curcuminoids increased the percentage of G2/M phase cell populations in the treated groups. Treating HNO97 cells with curcuminoids led to cell shrinking and increased detached cells, which are the typical appearance of apoptotic cells. Moreover, flow cytometry analysis revealed that curcuminoids significantly induced apoptosis in a time-dependent manner. Furthermore, as a response to curcuminoids treatment, comet tails were formed in cell nuclei due to the induction of DNA damage. Curcuminoids treatment reduced the colony formation capacity of HNO97 cells and induced morphological changes. Overall, these findings demonstrate that curcuminoids can in vitro inhibit HNC proliferation and metastasis and induce apoptosis.

O carcinoma de células escamosas oral (OSCC) é um tumor maligno do câncer de cabeça e pescoço (HNC). As recentes abordagens terapêuticas usadas para tratar o câncer têm efeitos colaterais adversos. Os agentes naturais que exibem atividades anticâncer são geralmente considerados como tendo um potencial terapêutico robusto. Curcuminoides, um dos principais compostos ativos da erva cúrcuma, são usados como agente terapêutico para várias doenças, incluindo câncer. Neste estudo, a citotoxicidade dos curcuminoides foi investigada contra a linha de células OSCC HNO97. Nossos dados mostraram que os curcuminoides inibem significativamente a proliferação de HNO97 de forma dependente do tempo e da dose (IC50 = 35 μM). A análise do ciclo celular demonstrou que os curcuminoides aumentaram a porcentagem de populações de células da fase G2 / M nos grupos tratados. O tratamento das células HNO97 com curcuminoides levou ao encolhimento celular e ao aumento das células destacadas, que são a aparência típica das células apoptóticas. Além disso, a análise de citometria de fluxo revelou que os curcuminoides induziram significativamente a apoptose de uma maneira dependente do tempo. Além disso, em resposta ao tratamento com curcuminoides, caudas de cometa foram formadas nos núcleos das células devido à indução de danos ao DNA. O tratamento com curcuminoides reduziu a capacidade de formação de colônias das células HNO97 e induziu alterações morfológicas. No geral, esses achados demonstram que os curcuminoides podem inibir in vitro a proliferação e metástase de HNC e induzir apoptose.

Toxicology of a Peruvian botanical remedy to support healthy liver function.

BACKGROUND: The purpose of these studies was to determine the safety of a botanical treatment for supporting healthy liver function developed in Peru. The formulation, A4+, contains extracts of Curcuma longa L. rhizome (A4R), Cordia lutea Lam. flower (A4F) and Annona muricata L. leaf (A4L). The tests were used to support an application for a non-traditional Natural Health Product Licence from the Natural Health Product Directorate of Health Canada and future clinical trials. METHODS: Besides reviewing the scientific and clinical information from Peru on the ingredients and conducting an initial Ames test for mutagenicity, we analysed A4+ for its chemical profile and tested genotoxicity (micronucleus test) and general toxicity (28-day repeated dose). RESULTS: A4+ and extracts from the three plants provided distinctive chemical fingerprints. A4L contained acetogenins, requiring a second chromatographic method to produce a specific fingerprint. The Ames test proved positive at the highest concentration (5,000 µg/mL) but A4+ showed no evidence of genotoxicity in the more specific mouse micronucleus test. The 28-day repeated dose (general toxicity) study in rats showed no toxicity at 2,000 mg/kg. CONCLUSIONS: We conclude that under the conditions of these studies, A4+ shows no evidence of toxicity at the levels indicated. A no observed adverse effect level (NOAEL) of 2,000 mg/kg was assigned.

Evaluación de la bioactividad de plantas medicinales cultivadas en el Perú usando la prueba de letalidad de Artemia salina / Bioactivity of medicinal plants cultivated in Peru using Artemia salina lethality test

Objetivo. Determinar la bioactividad de trece plantas medicinales peruanas a través de su capacidad citotóxica. Materiales y métodos. Se elaboraron extractos acuosos, hidroalcohólicos, o zumos liofilizados de las especies vegetales seleccionadas. La citotoxicidad in vitro fue evaluada usando la prueba de letalidad de Artemia salina, con la determinación de la concentración letal media (CL50). El potencial citotóxico de las muestras de extractos evaluados, se clasificaron en: a) no tóxico: CL50 > 1000 µg/ mL; b) baja toxicidad: 500 < CL50 ≤ 1000 µg/ mL; c) toxicidad moderada: 100 < CL50 ≤ 500 µg/ mL, y d) alta toxicidad: CL50 < 100 µg/ mL. Resultados. Los diferentes extractos del rizoma de Curcuma longa mostraron una potente actividad citotóxica, con CL50 entre 20,67 ± 7,04 y 98,14± 2,64 ug/mL. Los extractos de rizoma de Zingiber officinale, del fruto de Physalis angulata y la planta entera de Physalis angulata también mostraron actividad citotóxica con CL50 de 87,15±18,17, 323,48±18,85 y 328,92±23,08 ug/mL, respectivamente. Conclusión. Se encontró actividad citotóxica en los extractos de los rizomas de Curcuma longa, Zingiber officinale, así como el fruto y planta entera de Physalis angulata. Futuros estudios podrán determinar si la flora cultivada en el Perú puede ser una fuente para el desarrollo futuro de agentes antitumorales.

Objective. To determine the bioactivity of 13 Peruvian medicinal plants through their cytotoxic capacity. Material and methods. Aqueous, hydroalcoholic extracts or lyophilized juices of the selected plant species were elaborated. In vitro cytotoxicity was evaluated using the Artemia salina lethality test, with the determination of the mean lethal concentration (LC50). The cytotoxic potential of the samples of evaluated extracts was classified into: a) non-toxic: LC50> 1000 µg / mL, b) low toxicity: 500 < LC50 ≤ 1000 µg / mL, c) moderate toxicity: 100 < LC50≤ 500 µg / mL, and d) high toxicity: LC50 <100 µg / mL. Results. The different extracts of the Curcuma longa's rhizome showed a potent cytotoxic activity, with LC50 between 20.67 ± 7.04 and 98.14 ± 2.64 µg / mL. Zingiber officinale rhizome, Physalis angulate fruit and Physalis angulata whole plant extracts, also showed cytotoxic activity with LC50 of 87.15 ± 18.17, 323.48 ± 18.85 and 328.92 ± 23.08 µg / mL, respectively. Conclusion. Cytotoxic activity was found in the extracts of Curcuma longa, Zingiber officinale rhizomes, as well as Physalis angulata fruit and whole plant extracts. Future studies will be able to determine if the flora cultivated in Peru could be a source for future development of antitumoral agents.

Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO.

Cytotoxicity of the rhizome of medicinal plants.

OBJECTIVE: To investigate the cytotoxicity of the crude ethanol extract of the rhizome of Zingiber zerumbet (Z. zerumbet) (L) Smith. and Curcuma zedoaria (C. zedoaria) Rosc. against Artemia salina Leach. METHODS: Fresh rhizomes of Z. zerumbet (L) Smith. and C. zedoaria Rosc. were extracted separately in cold with ethanol (2.5 L) and after concentration a brownish syrupy suspension of ethanol extracts of Z. zerumbet (L) Smith. and C. zedoaria Rosc. was obtained. The cytotoxic effect of the crude ethanol extracts of both plants was determined by brine shrimp lethality bioassay. RESULTS: Crude ethanol extracts of the rhizome of Z. zerumbet (L) Smith. showed the highest cytotoxicity (LC50 was 1.24 µg/mL) against brine shrimp nauplii as compared with C. zedoaria Rosc. (LC50 was 33.593 µg/mL) after 24 h of exposure. CONCLUSIONS: It can be concluded that the rhizome of Z. zerumbet (L) Smith. and C. zedoaria Rosc. can be used as a source of cytotoxic agent.

Estudio de toxicidad a 28 días, del extracto atomizado de rizoma de Curcuma longa (A4R), flores de Cordia lutea (A4F) y hojas de Annona muricata (A4L) en un modelo murino / Study of toxicity to 28 days, of the atomized extract of the rhizome of Curcuma longa (A4R), Cordia lutea flowers (A4F) and leaves of Annona muricata (A4L) in a murine model

La asociación de las tres plantas ha sido aprobada por la Institución de Salud en Canadá, bajo la forma de extracto lioilizado, la cual ha demostrado poseer efectos terapéuticos. Objetivos: Determinar la seguridad de la asociación del extracto atomizado del rizoma de Curcuma longa (A4R); lores de Cordia lutea (A4F) y hojas de Annona muricata (A4L) a una dosis repetida durante 28 días por vía oral en ratas. Materiales y métodos: Diseño experimental, se utilizaron 40 ratas Holtzman (20 machos ­ 20 hembras); se siguió las directrices o normas de la Organization for Economic Cooperation and Development (OECD) Norma 407; se administró el extracto atomizado durante 28 días por vía oral, se realizaron las observaciones, registro de signos y evolución semanal del peso corporal de los animales; al final, se extrajo muestra de sangre para estudio hematológico y bioquímico; posteriormente, fueron sacrificados para estudio anatomopatológico de hígado, riñón, corazón, médula, cerebro, páncreas, y bazo; se aplicó el ANOVA, considerando el valor p<0,05 para la significancia. Resultados: Al administrar la asociación en forma de extracto atomizado, se observó una evolución temporal homogénea del peso corporal. No hubo variación significativa en los niveles de glucemia, urea, colesterol, triglicéridos, bilirrubina indirecta, transaminasas (GPT­ GOT), fosfatasa alcalina ni hemoglobina (p>0,05); Conclusiones: Los hallazgos demuestran que el extracto atomizado del rizoma de Curcuma longa (A4R), las flores de Cordia lutea (A4F) y las hojas de Annona muricata (A4L) no es toxico en ratas, al ser administrado por un periodo de 28 días.

Oral dose-ranging developmental toxicity study of an herbal supplement (NT) and gallic acid in rats.

OBJECTIVE: To evaluate the combination of rhubarb, astragalus, red sage, ginger, and turmeric (mixture referred to as "NT") together with gallic acid for evidence of reproductive toxicity in rats. METHODS: Fifty virgin female rats were cohabited with male rats. Day 0 of potential pregnancy was evidence of spermatozoa on vaginal smear. The presumably pregnant rats were randomized to five groups of 10 individuals and were fed by daily gavage on days 6-20 of presumed gestation with one of the following: deionized water placebo, 21.6 mg/kg per day, 215 mg/kg per day, 430 mg/kg per day, or 860 mg/kg per day of a mixture of NT (20%) and gallic acid (80%). Cesarean section was performed on day 21. RESULTS: All 50 rats had one or more live fetuses and survived until they were killed. Body weight was reduced in the 860 mg/kg per day group compared with placebo: mean (SD), 406.8 (23.0) vs. 430.1 (27.7) g, P<0.05. There were no dose-related adverse events or differences between groups in uterine size, food intake, corpora lutea, implantations, litter size, number of live fetuses, and gender distribution of fetuses or fetal resorptions. There were no dead fetuses, and all placentae appeared normal. All rats and tissues were normal at necropsy. Fetal weights did not differ between groups, and there were no fetal abnormalities. CONCLUSION: The combination of NT and gallic acid gave no evidence of reproductive toxicity at 430 mg/kg per day or below, which is reassuring should this combination be used in the future as a dietary herbal supplement for the treatment of obesity.

Toxicity prediction of compounds from turmeric (Curcuma longa L).

Turmeric belongs to the ginger family Zingiberaceae. Currently, cheminformatics approaches are not employed in any of the spices to study the medicinal properties traditionally attributed to them. The aim of this study is to find the most efficacious molecule which does not have any toxic effects. In the present study, toxicity of 200 chemical compounds from turmeric were predicted (includes bacterial mutagenicity, rodent carcinogenicity and human hepatotoxicity). The study shows out of 200 compounds, 184 compounds were predicted as toxigenic, 136 compounds are mutagenic, 153 compounds are carcinogenic and 64 compounds are hepatotoxic. To cross validate our results, we have chosen the popular curcumin and found that curcumin and its derivatives may cause dose dependent hepatotoxicity. The results of these studies indicate that, in contrast to curcumin, few other compounds in turmeric which are non-mutagenic, non-carcinogenic, non-hepatotoxic, and do not have any side-effects. Hence, the cost-effective approach presented in this paper could be used to filter toxic compounds from the drug discovery lifecycle.

Análise preliminar da citotoxicidade dos aditivos alimentares urucum e cúrcuma / Cytotoxicity of the food additive annatto and turmeric

Este trabalho teve por objetivo avaliar a ação dos aditivos alimentares urucum e cúrcuma em células meristemáticas de pontas de raízes de Allium cepa nas doses de 5 e 10 g, nos tempos de exposição de 24 e 48 horas. Utilizou-se para cada dose um grupo de cinco bulbos de cebolas, que primeiramente foram enraizados em água destilada, e em seguida transferidos para as suas respectivas doses. Analisaram-se células em todo ciclo celular, totalizando 5.000 para cada controle e tempo de exposição. Os dados obtidos foram submetidos à análise estatística do Qui-quadrado (p<0,05). A partir dos resultados observou-se que as doses do urucum e do cúrcuma tiveram efeito antiproliferativo significativo sobre o ciclo celular deste sistema-teste. Também foi verificado número significativo de aberrações celulares nos dois tempos de exposição avaliados de todas as doses estudadas. Portanto, nas condições analisadas, o urucum e o cúrcuma mostraram-se citotóxicos e genotóxicos.

This study aimed to evaluate the effect of food additives annatto and turmeric tip cells of Allium cepa roots in doses of 5 or 10 g in exposure times of 24 and 48 hours. A group of five onion bulbs was used for each dose. Each dose was first embedded in distilled water and then transferred to their respective doses. Cells were analyzed throughout the cell cycle, totaling 5000 for each control and exposure time. The obtained data were subjected to statistical analysis Chi-square (p <.05). From the results it was observed that the doses of turmeric and annatto had significant antiproliferative effect on the cell cycle of this test system. They also found a significant number of cellular aberrations in the two exposure times evaluated all doses studied. Therefore, under the conditions studied, annatto and turmeric proved cytotoxic and genotoxic.

Bayesian inferences on umbrella orderings.

In regression applications with categorical predictors, interest often focuses on comparing the null hypothesis of homogeneity to an ordered alternative. This article proposes a Bayesian approach for addressing this problem in the setting of normal linear and probit regression models. The regression coefficients are assigned a conditionally conjugate prior density consisting of mixtures of point masses at 0 and truncated normal densities, with a (possibly unknown) changepoint parameter included to accommodate umbrella ordering. Two strategies of prior elicitation are considered: (1) a Bayesian Bonferroni approach in which the probability of the global null hypothesis is specified and local hypotheses are considered independent; and (2) an approach which treats these probabilities as random. A single Gibbs sampling chain can be used to obtain posterior probabilities for the different hypotheses and to estimate regression coefficients and predictive quantities either by model averaging or under the preferred hypothesis. The methods are applied to data from a carcinogenesis study.