Pharmacokinetic and toxicological prediction of the chemical constituents of the essential oil of the leaves of Croton heliotropiifolius Kunth.

The development of new drugs through studies of candidate molecules is a complex undertaking; however, computational or in silico approaches aimed at optimizing molecules with greater development potential are being utilized for predictions of pharmacokinetic properties such as absorption, distribution, metabolism and excretion (ADME) as well as toxicological parameters. The objective of this study was to examine in silico and in vivo pharmacokinetic and toxicological properties of the chemical constituents present in the essential oil of Croton heliotropiifolius Kunth leaves. The following Pubchem platform as well as Software SwissADME and PreADMET software were employed for in silico studies while micronucleus (MN) testing for in vivo determination of mutagenicity, using Swiss adult male Mus musculus mice. In silico findings demonstrated that all chemical constituents presented (1) high oral absorption (2) medium cellular permeability and (3) high blood brain permeability. As for toxicity, these chemical constituents exhibited low to medium risk of occurrence of cytotoxicity. Regarding in vivo evaluation, peripheral blood samples obtained from animals tested with the oil showed no significant differences in number of MN compared to negative controls. Data indicate that further investigations are necessary to corroborate the findings of this study. Our data suggest that essential oil extracted from Croton heliotropiifolius Kunth leaves may serve as a candidate for new drug development.

Ecotoxicology of Heavy Metal(loid)-Enriched Particulate Matter: Foliar Accumulation by Plants and Health Impacts.

Atmospheric contamination by heavy metal-enriched particulate matter (metal-PM) is highly topical nowadays because of its high persistence and toxic nature. Metal-PMs are emitted to the atmosphere by various natural and anthropogenic activities, the latter being the major source. After being released into the atmosphere, metal-PM can travel over a long distance and can deposit on the buildings, water, soil, and plant canopy. In this way, these metal-PMs can contaminate different parts of the ecosystem. In addition, metal-PMs can be directly inhaled by humans and induce several health effects. Therefore, it is of great importance to understand the fate and behavior of these metal-PMs in the environment. In this review, we highlighted the atmospheric contamination by metal-PMs, possible sources, speciation, transport over a long distance, and deposition on soil, plants, and buildings. This review also describes the foliar deposition and uptake of metal-PMs by plants. Moreover, the inhalation of these metal-PMs by humans and the associated health risks have been critically discussed. Finally, the article proposed some key management strategies and future perspectives along with the summary of the entire review. The abovementioned facts about the biogeochemical behavior of metal-PMs in the ecosystem have been supported with well-summarized tables (total 14) and figures (4), which make this review article highly informative and useful for researchers, scientists, students, policymakers, and the organizations involved in development and management. It is proposed that management strategies should be developed and adapted to cope with atmospheric release and contamination of metal-PM.

Risk assessment via genotoxicity, metabolism, apoptosis, and cell growth effects in a HepG2/C3A cell line upon treatment with Rubus rosifolius (Rosaceae) leaves extract.

RUBUS ROSIFOLIUS: Sm. (Rosaceae) is a plant traditionally used in Brazil and some other countries to treat diarrhea, stomach diseases, and as an analgesic, antimicrobial, antihypertensive, and as well as other pharmacological properties. The aim of this study was to examine cytotoxic and genotoxic effects of R. rosifolius leaves extract on HepG2/C3A cells and correlate these findings with the expression of mRNA to underlying mechanisms of action. At concentrations between 0.01 and 100 µg/ml, cytotoxic effects were not detected by the MTT assay. This was confirmed by mRNA induction of the CYP3A4 gene (by RT-qPCR assay). However, genotoxic effects occurred at treatments from 1 µg/ml extract (comet and micronucleus test). An increase in the number of cells in S phase was observed at 100 µg/ml, and an elevation in apoptotic cell number was found for all tested concentrations (10, 20, or 100 µg/ml) (cell cycle and apoptosis analysis by flow cytometry). The genotoxicity induced by the extract was the main cause of the rise in the number of cells undergoing apoptosis, as indicated by rise in mRNA of CASP7 gene, and elevation of cells in the S phase of the cell cycle at the higher tested concentrations, as an attempt to repair genetic damage that occurred. These observations suggest that, despite its pharmacological potential, the use of R. rosifolius leaves extract may pose a risk to the integrity of the genetic material of human cells.

Safety evaluation of orally-administered methanol extract of Muntingia calabura Linn. leaves: A sub-chronic toxicity study in Sprague Dawley rats.

Muntingia calabura (M. calabura), locally known as "kerukup siam" or "buah ceri" belongs to the family Muntingiaceae and has been scientifically demonstrated to exert various pharmacological activities. The objectives of the current study are to evaluate the antioxidant activities and to determine the subchronic toxicity of 90 days orally-administered methanol extract of M. calabura (MEMC) in male Sprague Dawley rats. The rats were randomly divided into four groups (n=6). Vehicle control received 8% tween 80 and treatment group received 50, 250 and 500 mg/kg of MEMC orally administered daily for 90 days. Blood collection was carried out to obtain the hematological and biochemical profile of the rats. The organs harvested were subjected to histopathological analysis. For the antioxidant test, the extract was subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging activity, total phenolic content (TPC) and phytochemical screening. Results obtained show that no adverse effects were observed during the experimental period. Hematological and biochemical analysis also showed no significant changes in this toxicity study. Besides, antioxidant analyses revealed that MEMC has higher DPPH- and SOD-radical scavenges activity as well as higher TPC value. In conclusion, M. calabura is safe for consumption and possesses beneficial antioxidant effect.

Evaluation of cytotoxic potential, oral toxicity, genotoxicity, and mutagenicity of organic extracts of Pityrocarpa moniliformis.

The objective of this study was to determine the cytotoxicity of organic extracts of P. moniliformis in vitro and identify the acute toxicity and genotoxicity in vivo. The leaves were extracted using three organic solvents (cyclohexane [EP1], ethyl acetate [EP2], and methanol [EP3]). Phytochemical qualitative analysis was performed by thin layer chromatography (TLC). Cytotoxicity tests were performed on human embryonic kidney (HEK) cells and J774 murine macrophages. Acute toxicity in mice was measured after intraperitoneal (ip) administration of 2000 mg/kg, while evaluation of genotoxicity and mutagenicity were assessed using the comet assay and the micronucleus (MN) test, respectively. The TLC analysis of the extracts revealed the presence of flavonoids, triterpenes, steroids, and saponins. In the cytotoxicity assay, extracts EP1 and EP3 altered proliferation of HEK cells, and all organic extracts increased the viability of J774 cells. In the toxicity tests, no deaths or behavioral alterations were observed in mice exposed to the acute dose of the extracts. Although some extracts led to changes in hematological and histological parameters, these results did not indicate physiological changes. In relation to the MN test and comet assay, no significant changes were detected in the DNA of the animals tested with the extracts EP1, EP2, and EP3. Thus, extracts of P. moniliformis were not considered to be toxic and did not induce formation of MN or damage to cellular DNA in the genotoxicity tests.

Toxicity of the spiny thick-foot Pachypodium.

PREMISE OF THE STUDY: Pachypodium (Apocynaceae) is a genus of iconic stem-succulent and poisonous plants endemic to Madagascar and southern Africa. We tested hypotheses about the mode of action and macroevolution of toxicity in this group. We further hypothesized that while monarch butterflies are highly resistant to cardenolide toxins (a type of cardiac glycoside) from American Asclepias, they may be negatively affected by Pachypodium defenses, which evolved independently. METHODS: We grew 16 of 21 known Pachypodium spp. and quantified putative cardenolides by HPLC and also by inhibition of animal Na+ /K+ -ATPase (the physiological target of cardiac glycosides) using an in vitro assay. Pachypodium extracts were tested against monarch caterpillars in a feeding bioassay. We also tested four Asclepias spp. and five Pachypodium spp. extracts, contrasting inhibition of the cardenolide-sensitive porcine Na+ /K+ -ATPase to the monarch's resistant form. KEY RESULTS: We found evidence for low cardenolides by HPLC, but substantial toxicity when extracts were assayed on Na+ /K+ -ATPases. Toxicity showed phylogenetic signal, and taller species showed greater toxicity (this was marginal after phylogenetic correction). Application of Pachypodium extracts to milkweed leaves reduced monarch growth, and this was predicted by inhibition of the sensitive Na+ /K+ -ATPase in phylogenetic analyses. Asclepias extracts were 100-fold less potent against the monarch compared to the porcine Na+ /K+ -ATPase, but this difference was absent for Pachypodium extracts. CONCLUSIONS: Pachypodium contains potent toxicity capable of inhibiting sensitive and cardenolide-adapted Na+ /K+ -ATPases. Given the monarch's sensitivity to Pachypodium, we suggest that these plants contain novel cardiac glycosides or other compounds that facilitate toxicity by binding to Na+ /K+ -ATPases.

In vitro and in vivo evaluation of the genotoxicity of Eriobotrya japonica leaf extract.

Eriobotrya japonica leaf is included in the Chinese Pharmacopoeia, and is widely used as a medicinal material in traditional medicine. The present study investigated the potential genotoxic effects of E. japonica leaf extract (EJE) using three standard battery systems. Genotoxicity tests were conducted following the test guidelines of the Organisation for Economic Cooperation and Development (OECD) and Ministry of Food and Drug Safety (MFDS), with application of Good Laboratory Practice. The bacterial reverse mutation test was conducted using the pre-incubation method in the presence or absence of the metabolic activation system (S9 mixture). The in vitro chromosome aberration test was performed using cultured Chinese hamster lung cell line in the presence or absence of the S9 mixture. The in vivo micronucleus test was performed using ICR mice. The bacterial reverse mutation test with Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2uvrA showed that EJE did not induce gene mutations at any dose level in all the strains tested. EJE also did not show any chromosomal aberrations in the in vitro chromosomal aberration test and in the in vivo micronucleus test. These results showed that EJE did not induce mutagenicity or clastogenicity in either in vitro or in vivo systems.

In vivo assessment of cyto/genotoxic, antigenotoxic and antifungal potential of Costus spiralis (Jacq.) Roscoe leaves and stems.

Costus spiralis is a Brazilian native plant used in popular medicine, but the safety of this therapeutic use needs investigation. So, the aim of this study was to evaluate the cytogenotoxic and antigenotoxic effects of C. spiralis leaves or stems aqueous extracts on Allium cepa root cells. Moreover, a phytochemical screening and an antioxidant and antifungal activities evaluation were performed. C. spiralis aqueous extracts presented cytotoxicity, but no mutagenicity was observed. When the antigenotoxicity was evaluated, C. spiralis leaves aqueous extract presented preventive and modulatory effects on A. cepa root cells, reducing the sodium azide cytogenotoxic effects. In contrast, C. spiralis stems aqueous extract enhanced the sodium azide cytogenotoxicity in some conditions. The phytochemical screening revealed the presence of phenolic compounds in C. spiralis. When total phenolic content was determined, the leaves presented 73% more phenolic content than stems. Corroborating this data, C. spiralis leaves antioxidant potential was 30% higher than C. spiralis stems. However, these extracts did not present antifungal activity against Candida spp. In conclusion, empirical utilization of C. spiralis aqueous extracts should be avoided. Moreover, the cytotoxic effect of C. spiralis leaves and stems can play an important role in anticancer therapy and must be deeply studied.

Treatment-related changes after short-term exposure of SD rats to Aloe vera whole-leaf freeze-dried powder.

Aloe vera is a widely used natural herb from which many sorts of commercial products have been derived using different preparation technologies. Aloe whole-leaf powder is one of the most popular subtypes. The long-term impact of aloe products has already been reported; however, there have been few studies about short-term exposure, and especially about the relative impact of Aloe vera whole-leaf freeze-dried powder (AWFP). To provide more toxicological data and to document the early changes induced by AWFP, in this study 120 SD rats were divided into four groups (control and 400/1200/2000 mg/kg treatment groups) and were administered AWFP once daily by oral gavage for 28 consecutive days, followed by a two week recovery phase. The results showed that AWFP could induce soft/loose changes in faeces. Significantly decreased white blood cell (WBC) counts, associated with reduced lymphocyte counts were also noted. The relative organ weight, including both organ-to-body weight ratio and organ-to-brain weight ratio of kidneys, was significantly increased in 2000 mg/kg compared with that in controls. Histopathologically, pigmentation in the kidneys and increased mucosal thickness in colon were also noted in a dose response groups. Other changes observed in the study were not considered to be treatment related, and 400 mg/kg was considered as the no-observed-adverse-effect level. The study provided clear evidence of treatment-related changes with a short-term exposure to AWFP. This is also the first report of the early colon morphologic changes associated with stool changes noted previously in-life phase, providing additional toxicity data which will contribute to our understanding about the short-term usage of AWFP as a remedy.

Microcystin accumulation and potential effects on antioxidant capacity of leaves and fruits of Capsicum annuum.

Surface water, often used for irrigation purposes, may sometimes be contaminated with blooming cyanobacteria and thereby may contain their potent and harmful toxins. Cyanotoxins adversely affect many terrestrial plants, and accumulate in plant tissues that are subsequently ingested by humans. Studies were undertaken to (1) examine the bioaccumulation of microcystins (MCs) in leaves and fruits of pepper Capsicum annuum and (2) examine the potential effects of MCs on antioxidant capacity of these organs. Plants were irrigated with water containing MCs for a period of 3 mo. Data showed that MCs did not accumulate in leaves; however, in fruits the presence of the MC-LR (0.118 ng/mg dry weight) and dmMC-LR (0.077 ng/mg dry weight) was detected. The concentrations of MC-LR in fruit approached the acceptable guideline values and tolerable daily intake for this toxin. Lipid peroxidation levels and flavonoids content were significantly enhanced in both organs of treated plants, while total phenolic concentrations were not markedly variable between control and treated plants. Significant decrease in 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging capacity was noted for both organs. The levels of superoxide anion in fruits and hydroxyl radical in leaves were markedly reduced. Data suggest that exposure to MCs significantly reduced antioxidant capacity of experimental plants, indicating that MCs affected antioxidant systems in C. annuum.

Evaluation of the cytotoxicity (HepG2) and chemical composition of polar extracts from the ruderal species Coleostephus myconis (L.) Rchb.f.

Coleostephus myconis (L.) Rchb.f. (Asteraceae) is a highly disseminated plant species with ruderal and persistent growth. Owing to its advantageous agronomic properties, C. myconis might have industrial applications. However, this species needs to be comprehensively characterized before any potential use. In a previous study, the phenolic composition and antioxidant activity of different C. myconis tissues were characterized. This investigation was extended to examine the cytotoxic potential of selected plant tissues (flowers and green parts) using a HepG2 cell line by utilizing the lysosomal neutral red uptake assay or mitochondrial (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. In addition, the macronutrients content, lipophilic compounds (fatty acids, tocopherols), and amino acids were also determined. C. myconis flowers were used in the senescence stage, which was previously identified as the stage that presented maximal phenolic content and highest antioxidant activity. In contrast, stems and leaves were employed due to their high biomass proportion. Regarding cytotoxicity, mitochondrial and lysosomal damage was only significant when HepG2 cells were exposed to the highest extract concentrations (stems and leaves, 0.9 mg/ml; senescent flowers, 0.3 mg/ml). Chemically, the senescent flowers were mostly characterized by their high levels of fat, amino acids (especially threonine), oleic acid, ß-, and γ-tocopherol, while stems and leaves contained high concentrations of carbohydrates, linolenic acid, and α-tocopherol. In general, these results provide information regarding the threshold concentrations of C. myconis extracts that might be used in different applications without toxicity hazards.

Neuroprotective effect of Moringa oleifera leaf extract on aluminium-induced temporal cortical degeneration.

Aluminium (Al), one of the metals implicated in neurodegeneration easily gain access to the nervous system through its presence in many manufactured foods, medicines and drinking water, and causes neurotoxicity utilizing the reactive oxygen specie pathway. The need to curtail these effects on the nervous system motivated the use of the plant Moringa oleifera (MO). This study thus, investigated the neuroprotective effects of MO leaf extract on aluminium-induced temporal cortical degeneration in rats. 24 male albino Wistar rats were grouped (n = 6) into control (1 ml/kg distilled water), l00 mg/kg aluminium chloride (AlCl3), 300 mg/kg MO, and 100 mg/kg AlCl3 and 300 mg/kg MO groups. The administration lasted for 28 days and the rats were sacrificed on day 29 by perfusion-fixation after blood was obtained for serum Al estimation. The brain tissues were then routinely processed for some histological and immunnolabelling studies. There was no significant difference in serum Al in the test groups. Histological results showed atrophied and karyorrhetic cells with loss of Nissl substance in the temporal cortex of the AlCl3 group, while no adverse effect was observed in the cytoarchitecture of the temporal cortex and Nissl substance of the MO group. However, groups which were administered AlCl3 simultaneously with MO extract showed less degenerative features in the cyto-architecture of the temporal cortex with normal Nissl substance staining. There was increased neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP) expressions in the AlCl3 group, while the MO group also showed increased NSE but decreased GFAP expression. However, the group which were administered AlCl3 simultaneously with MO extract showed less expression of NSE and GFAP. In conclusion, MO protects against Al-induced neurotoxicity of the temporal cortex of rats.

In vitro toxicological assessment of Arrabidaea brachypoda (DC.) Bureau: Mutagenicity and estrogenicity studies.

Arrabidaea brachypoda (DC.) Bureau is a shrub native Cerrado, known as "cipó-una", "tintureiro" or "cervejinha do campo" and popularly used in Southeastern and Northeastern Brazil to treatment of kidney stones and painful joints (arthritis). Nevertheless, scientific information regarding this species is scarce, and there are no reports related to its possible estrogenic and mutagenic effects. Thus, the principal objective of this study was to assess the mutagenic and estrogenic activities of the hydroalcoholic extracts of the leaves, stalks, roots, their respective fractions and isolated compounds of A. brachypoda. The mutagenic activity was evaluated by the Ames test on Salmonella typhimurium strains TA98, TA97a, TA100 and TA102, in the absence (-S9) and presence (+S9) of metabolic activation system. In the RYA was used Saccharomyces cerevisiae engineered strain BY4741 (MATaura3Δ0 leu2Δ0 his3Δ1 met15Δ0) which reproduce the natural pathway of genetic control by estrogens in vertebrate cells; it has the advantage of its simplicity and a high throughput. All extracts and aqueous fraction of leaves A. brachypoda were mutagenic. The crude extract is more active than the fraction, suggesting a synergic effect. Only hydroalcoholic extracts of leaves and roots of A. brachypoda showed significant estrogenic activity, with ERα-dependent transcriptional activation activity. The obtained results in this study showed the presence of compounds capable of interacting with the estrogen receptor and to induce damage in the genetic material. Thus, we demonstrated the risk which the population is subjected due to indiscriminate use of extracts without detailed study.

Chronic toxicity evaluation of Morinda citrifolia fruit and leaf in mice.

Noni (Morinda citrifolia) leaf and fruit are used as food and medicine. This report compares the chronic toxicity of Noni fruit and edible leaf water extracts (two doses each) in female mice. The 6 months study showed the fruit extract produced chronic toxicity effects at the high dose of 2 mg/ml drinking water, evidenced through deteriorated liver histology (hepatocyte necrosis), reduced liver length, increased liver injury marker AST (aspartate aminotransferase) and albumin reduction, injury symptoms (hypoactivity, excessive grooming, sunken eyes and hunched posture) and 40% mortality within 3 months. This hepatotoxicity results support the six liver injury reports in humans which were linked to chronic noni fruit juice consumption. Both doses of the leaf extracts demonstrated no observable toxicity. The hepatotoxicity effects of the M. citrifolia fruit extract in this study is unknown and may probably be due to the anthraquinones in the seeds and skin, which had potent quinone reductase inducer activity that reportedly was 40 times more effective than l-sulforaphane. This report will add to current data on the chronic toxicity cases of Morinda citrifolia fruit. No report on the chronic toxicity of Morinda citrifolia fruit in animal model is available for comparison.

Acute and sub-chronic toxicity of Cajanus cajan leaf extracts.

CONTEXT: The leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse bioactivities, but little safety data are reported. OBJECTIVE: This study examines the toxicological profiles of C. cajan leaf extracts. MATERIALS AND METHODS: The leaves were extracted by water or 90% ethanol to obtain water or ethanol extract (WEC or EEC). EEC was suspended in water and successively fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker compounds of the extracts were monitored by high-performance liquid chromatography (HPLC). Kunming mice were administered with a single maximum acceptable oral dose (15.0 g/kg for WEC, EEC and BEC and 11.3 g/kg for DEC) to determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity investigation, Sprague-Dawley rats were orally given WEC or EEC at 1.5, 3.0 or 6.0 g/kg doses for four weeks and observed for two weeks after dosing to determine toxicological symptoms, histopathology, biochemistry and haematology. RESULTS: Flavonoids and stilbenes in the extracts were assayed. In acute toxicity test, no mortality and noted alterations in weight and behavioural abnormality were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic toxicity study, no mortality and significant variances in haematological and biochemical parameters or organ histopathology were observed, but increased kidney weight in 3.0 g/kg WEC- or 3.0 and 6.0 g/kg EEC-treated female rats, and reduced testes and epididymis weight in EEC-treated male rats were recorded. These changes returned to the level of control after recovery period. CONCLUSION: Acute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.

Cytotoxicity and anti-Leishmania amazonensis activity of Citrus sinensis leaf extracts.

CONTEXT: Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease characterized by lesional polymorphism and the commitment of skin surface. Previous reports demonstrated that the Citrus genus possess antimicrobial activity. OBJECTIVE: This study evaluated the anti-L. amazonensis activity of Citrus sinensis (L.) Osbeck (Rutaceae) extracts. MATERIALS AND METHODS: Citrus sinensis dried leaves were subjected to maceration with hexane (CH), ethyl acetate (CEA), dichloromethane/ethanol (CD/Et - 1:1) or ethanol/water (CEt/W - 7:3). Leishmania amazonensis promastigotes were treated with C. sinensis extracts (1-525 µg/mL) for 120 h at 27 °C. Ultrastructure alterations of treated parasites were evaluated by transmission electron microscopy. Cytotoxicity of the extracts was assessed on RAW 264.7 and J774.G8 macrophages after 48-h treatment at 37 °C using the tetrazolium assay. In addition, Leishmania-infected macrophages were treated with CH and CD/Et (10-80 µg/mL). RESULTS: CH, CD/Et and CEA displayed antileishmanial activity with 50% inhibitory activity (IC50) of 25.91 ± 4.87, 54.23 ± 3.78 and 62.74 ± 5.04 µg/mL, respectively. Parasites treated with CD/Et (131.2 µg/mL) presented severe alterations including mitochondrial swelling, lipid body formation and intense cytoplasmic vacuolization. CH and CD/Et demonstrated cytotoxic effects similar to that of amphotericin B in the anti-amastigote assays (SI of 2.16, 1.98 and 1.35, respectively). Triterpene amyrins were the main substances in CH and CD/Et extracts. In addition, 80 µg/mL of CD/Et reduced the number of intracellular amastigotes and the percentage of infected macrophages in 63% and 36%, respectively. CONCLUSION: The results presented here highlight C. sinensis as a promising source of antileishmanial agents.

Evaluation of cytotoxic and antiviral activities of aqueous leaves extracts of different plants against foot and mouth disease virus infection in farming animals.

Cytotoxic and antiviral activity of aqueous leaves extracts of three plants: Azadirachta indica, Moringa oleifera and Morus alba against Foot and Mouth disease virus (FMDV) were determined using MTT assay (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide). Eight different concentrations of each plant were evaluated. Cytotoxic and antiviral activity of each extract was evaluated as cell survival percentage and results were expressed as Means ± S.D. From the tested plant extracts, Azadirachta indica & Moringa oleifera exhibited cytotoxicity at 200 & 100 µ/ml respectively. In case of antiviral assay, Moringa oleifera showed potent antiviral activity (p<0.05) while Azadirachta indica showed significant antiviral activity in the range of 12.5-50 µ/ml & 50-100 µ/ml respectively. In contrast no anti-FMDV activity in the present study was observed with Morus alba, although all the tested concentrations were found to be safe.

Evaluation of the toxicokinetics and apoptotic potential of ethanol extract from Echinodorus macrophyllus leaves in vivo.

This study evaluates the toxicological, genotoxic, mutagenic and apoptotic potential of an in vivo assay from Echinodorus macrophyllus extract (EEM). The acute toxicity test used 02 groups (n = 5) of female Wistar rats: negative control group (saline) and experimental group (2000 mg/kg b.w. EEM), both orally administered (gavage) at single doses and monitored for 14 days. To assess the genotoxic, mutagenic and apoptotic potential, 50 male Swiss mice were divided into 5 groups (n = 10): Group I: negative control (saline solution 0.1 ml/10 g b.w.); Group II: positive control (cyclophosphamide 100 mg/kg b.w.) intraperitoneally administered; groups III-V received EEM at 500, 1000 and 2000 mg/kg b.w., respectively. Groups I, III-V received oral administrations (gavage). The results showed that there was no acute lethality or any signs of acute toxicity, indicating that LD50 is greater than 2000 mg/kg b.w. The groups treated with EEM showed no genotoxic or mutagenic activity and did not induce apoptosis in the liver and kidney. Therefore, EEM showed no acute toxicity and at doses of 500, 1000 and 2000 mg/kg b.w. absence of genotoxicity, mutagenicity and no apoptotic events were observed.