Assessment of the mutagenic activity of aversectin C]

Aversectin C was evaluated for mutagenic activity in the Ames test with Salmonella typhimurium TA 97, TA 98 and TA 100, in the dominant lethal assay on uninbred albino rats in a dose of 2.25 mg/kg body weight (1/40 of the LD50) and in the metaphase test on F1CBAxC57BI/6 mice in a dose of 8.2 mg/kg body weight (1/5 of the LD50). The agent showed no mutagenic activity in any of the tests. The anaphase test on F1CBAxC57BI/6 mice revealed no antimitotic activity of aversectin C.     

Safety and toxicological evaluation of a novel niacin-bound chromium (III) complex

Chromium is an essential trace element required for normal protein, fat and carbohydrate metabolism. It also helps in energy production and increasing lean body mass. Niacin-bound chromium (NBC) is a unique form of bioavailable chromium that promotes healthy lipid profile. This study was focused on determining the broad spectrum safety of NBC. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicities of NBC were evaluated. Ames bacterial reverse mutation assay, mouse lymphoma test and a dose-dependent 90-day subchronic toxicity were also conducted. In safety studies, the acute oral LD(50) of NBC was found to be greater then 5000 mg/kg in both male and female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. The acute dermal LD(50) of NBC was found to be >2000 mg/kg. The primary skin irritation test was conducted with NBC on New Zealand Albino rabbits. NBC was classified as slightly irritating. The primary eye irritation test was conducted with NBC on rabbits. NBC was classified as practically non-irritating to the eye. NBC did not induce mutagenic effects in the bacterial reverse mutation test in five Salmonella typhimurium strains (TA1535, TA98, TA100, TA97a and TA102), either with or without metabolic activation. Similarly, NBC did not induce mutagenic effects in the mammalian cell gene mutation test in L5178Y mouse lymphoma cells TK (+/-), either with or without metabolic activation. A dose-dependent 90-day subchronic toxicity study demonstrated no significant changes in selected organ weights individually and as percentages of body and brain weights. NBC supplementation did not cause changes in hepatic lipid peroxidation or DNA fragmentation after 30, 60 or 90 days of treatment. Hematology, clinical chemistry and histopathological evaluations did not show any adverse effects in all organs tested. Taken together, the above results indicate a broad spectrum of safety for NBC.     

The genetic toxicity of 3,3′,4,4′-tetrachloroazobenzene and 3,3′,4,4′-tetrachloroazoxybenzene: discordance between acute mouse bone marrow and subchronic mouse peripheral blood micronucleus test results

3,3′,4,4′-Tetrachloroazobenzene (TCAB) and 3,3′,4,4′-tetrachloroazoxybenzene (TCAOB) are dioxin-like chemicals that were investigated for toxicity in 13-week gavage studies in male and female B6C3F₁ mice and F344N rats by the National Toxicology Program. As part of the comprehensive toxicological investigation of these chemicals, peripheral blood smears from mice treated 5 days per week for 13 weeks with 0.1–30 mg/kg/day TCAB or TCAOB were analyzed for the frequency of micronucleated (MN) normochromatic erythrocytes (NCE). Both chemicals produced significant increases in MN-NCE in male and female mice. In contrast to these positive results in subchronic exposure studies, no significant increases were seen in acute bone marrow MN tests in male mice administered three daily injections of 50–200 mg/kg/day TCAB and TCAOB. The results with TCAB and TCAOB suggest that the routine integration of MN tests with subchronic toxicity studies may allow detection of mutagenic activity for some chemicals that fail to elicit responses in short-term, high dose tests. In addition, the integration of mutagenicity tests into general toxicity tests reduces the use of laboratory animals and the cost of the testing.     

Safety and toxicological evaluation of Rhizopora mucronata (a mangrove from Vellar estuary,India): assessment of mutagenicity,genotoxicity and in vivo acute toxicity

The present was carried out to evaluate the toxicity of methanolic leaf extract of Rhizophora mucronata (MERM) under in vivo and in vitro conditions. Mutagenicity of MERM (up to 4,000 μg/plate) evaluated by Salmonella/microsome assay (TA98, TA100, TA1535 and TA1538 strains), with or without metabolic activation showed no mutagenic effect in any of the tester strain. Evaluation of genotoxicity (comet assay) and cytotoxicity in PBMC revealed that MERM showed no significant difference in comet tail moment (TM) and tail scores and cytotoxicity up to 24 h respectively. In acute toxicity studies, oral administration of single doses of MERM (250–2,000 mg/kg) in Wistar rats produced neither mortality nor any noticeable changes in behavior. Hematological and biochemical parameters showed no difference, except for a significant increase in ALT and AST at the highest dose. Histopathological findings revealed hepatotoxicity and neurotoxicity at highest dose of extract. In subacute toxicity studies administration of MERM (1,000 mg/kg) for 28 consecutive days neither altered the body weight gain nor behavioral parameters. No significant change was observed in the hematological and biochemical parameters analyzed. Histopathological examination showed normal architecture suggesting no morphological disturbances. Collectively, these data demonstrate that consumption of MERM for various medicinal purpose is safe.     

The genetic toxicity of 3,3',4,4'-tetrachloroazobenzene and 3,3',4, 4'-tetrachloroazoxybenzene: discordance between acute mouse bone marrow and subchronic mouse peripheral blood micronucleus test results

3,3',4,4'-Tetrachloroazobenzene (TCAB) and 3,3',4, 4'-tetrachloroazoxybenzene (TCAOB) are dioxin-like chemicals that were investigated for toxicity in 13-week gavage studies in male and female B6C3F(1) mice and F344N rats by the National Toxicology Program. As part of the comprehensive toxicological investigation of these chemicals, peripheral blood smears from mice treated 5 days per week for 13 weeks with 0.1-30mg/kg/day TCAB or TCAOB were analyzed for the frequency of micronucleated (MN) normochromatic erythrocytes (NCE). Both chemicals produced significant increases in MN-NCE in male and female mice. In contrast to these positive results in subchronic exposure studies, no significant increases were seen in acute bone marrow MN tests in male mice administered three daily injections of 50-200mg/kg/day TCAB and TCAOB. The results with TCAB and TCAOB suggest that the routine integration of MN tests with subchronic toxicity studies may allow detection of mutagenic activity for some chemicals that fail to elicit responses in short-term, high dose tests. In addition, the integration of mutagenicity tests into general toxicity tests reduces the use of laboratory animals and the cost of the testing.     

Toxicological Study and Oxidative Stress Evaluation for Safety Assessment of Xylanase Preparations in Wistar Rats

Acute and 90‐day subchronic oral toxicity studies were conducted to establish the safety evaluation of xylanases preparations. A potential oxidative stress evaluation was also performed through testing the generation of oxidative radicals, depletion of antioxidants via oxidative modification of lipids, proteins and DNA of organ cells. During the subchronic oral toxicity study, no mortality was observed, obvious treatment‐related clinical signs and urinalysis parameters were in normal range. Differences in some hematological parameters, biochemistry, relative organ weight, and histopathology examinations between the treated group and the control group were not judged to be adverse. Our results indicated that the no‐observed‐adverse‐effect level for xylanases was 1,500 TXU/kg/day and the plasma antioxidant assays showed that these xylanases did not produce free‐radicals nor oxidative injuries. On the basis of the bacterial reverse mutation assay data, it is concluded that the expressed xylanase in Pichia pastoris do not present any mutagenic potential when tested in relevant genotoxicological assays.     

In Vivo Assessment of Immunogenicity and Toxicity of the Bacteriocin TSU4 in BALB/c Mice

Bacteriocin TSU4 is a novel antimicrobial peptide isolated from Catla catla gut isolate Lactobacillus animalis TSU4. It has been reported for its potential antimicrobial activity against fish pathogens and food spoilage bacteria. In vivo safety evaluation is necessary to determine its immunogenicity, toxicity, and importance in real-life applications. The present study was designed to evaluate the immunogenicity, acute and sub-chronic toxicity of bacteriocin TSU4 in BALB/c mice to ensure its safety in industrial application. Male BALB/c mice were administered intraperitoneally for immunogenicity assessment, by oral gavage with 50, 100, and 200 mg/kg/body weight for acute test and 0.5 mg/kg/day dose of bacteriocin TSU4 for sub-chronic toxicity test. Neither mortality nor any infections were observed during experimental period. There was no major increase in antibody titer during the immunogenicity test, and no mortality was observed during acute or sub-chronic toxicity tests. The LD₅₀ value of bacteriocin TSU4 was found to be higher than 200 ± 0.45 mg/kg. No significant change in the serum biochemical markers, histopathological analysis and visual observation in spleen sizes was observed. These findings revealed that bacteriocin TSU4 is a non-immunogenic, safe, non-toxic, and could be a potential candidate for industrial applications in food preservation and aquaculture industries.     

Toxicity profiling of the ethanolic extract of Citrullus lanatus seed in rats: behavioral,biochemical and histopathological aspects

Citrullus lanatus (Cucurbitaceae) is conventionally used for the treatment of urinary tract infection, renal stones, hypertension, diabetes and diarrhoea. Current study evaluates acute and 28 days repeated toxicity ethanolic extract of C. lanatus seed (EECLS) in Wistar rats to measure its safety profile. The single dose (2000 mg/kg BW) of EECLS was administered while in 28 days repeated study 250, 500 and 1000 mg/kg BW were administered orally in rats. Parameters such as biochemical, haematological and histopathological were analysed in subacute toxicity study. During study, no apparent sign of toxicity, behavioural changes and mortality were detected in acutely exposed animals. In 28 days repeated toxicity study, rats did not show significant changes in behaviour, gross pathology, body weight, biochemical and haematological parameters. Abridged serum glucose and cholesterol levels during the study designate their roles in treatment of hyperglycaemic and hyperlipidaemic conditions. No significant difference was observed in histopathology of liver and kidneys of treated rats. The current investigation demonstrated that EECLS is non-toxic below 1000 mg/kg BW and provides protection to some body organs. The data propose that LD₅₀ of EECLS was greater than 2000 mg/kg BW and the no observed adverse effect level (NOAEL) of EECLS was at the dose of 1000 mg/kg in rats. Taken together, our finding suggests that, EECLS is safe and provides some protection to body organs; also, its extract can be used for further preclinical and clinical evaluation for its therapeutic activity.     

粘细菌Corallococcus sp. strain EGB及其培养发酵液的安全性评估

【目的】研究粘细菌Corallococcus sp. strain EGB及其细胞培养发酵液的毒理安全性,为菌株EGB作为新型生防微生物菌剂的开发和环境施用安全性提供一定的科学基础。【方法】通过Ames试验、小鼠骨髓嗜多染红细胞微核试验和小鼠睾丸染色体畸变试验测定粘细菌EGB菌体及其细胞培养发酵液的遗传毒性;通过经口灌胃的方式测定粘细菌EGB菌体及其细胞培养发酵液对ICR小鼠的急性毒性和28d亚急性毒性。【结果】Ames试验、微核试验和精母细胞染色体畸变试验结果表明,与对照组相比,EGB菌体及其细胞培养发酵液无基因突变能力,对ICR小鼠无明显的遗传毒性。EGB菌体及其细胞培养发酵液对ICR小鼠的急性经口半致死剂量(LD50)>10g/kg BW (body weight);连续灌胃28 d后,处理组ICR小鼠的体重变化、采食饮水、血液生化指标、血常规、主要脏器指数和主要器官病理切片与对照组相比无显著差异(P<0.05)。【结论】粘细菌EGB菌体及其细胞培养发酵液的毒理安全性属于无毒类别,粘细菌的生物安全性使其在工农业领域的植物病害控制和生物转化等方面具有潜在的应用价值。     

Abortifacient principle of Achyranthes aspera Linn

Achyranthes apsera is an abundant indigenous herb in India. Extracts of the whole plant had shown an abortifacient effect in mice. Maximal activity was in the benzene extract which was tested. The drug, in olive oil, was given orally to rabbits in doses of 50 mg/kg of body weight on the 8th day postcoitum. Laparotomy was done on the 11th day. No implantation sites were found. However, ovaries contained prominent corpus luteum, indicating that the drug had prevented pregnancy. In rats, the drug was given orally as a single dose of 50 mg/kg of body weight on the 6th or 7th day after mating. No effect was observed. In mice the drug was given at a single dose of either 10, 15, 25, or 50 mg/kg of body weight. For toxicity tests in mice, a single dose of 1000 mg/kg of body weight was given. After 1 month animals were autopsied and the organs examined. The drug was nontoxic. For a chronic toxicity test 75 mg/kg of body weight was given every 21 days. After 6 months of drug treatment, blood and tissue samples were examined. No toxic effects were observed. For a teratogenic study, 15 mated female mice were fed 10 or 25 mg/kg of body weight on Day 6 of gestation. 3 generations of offspring showed no malformations. In mice, abortifacient effects were noted with a maximum activity at 50 mg/kg of body weight. The drug showed no estrogenic, antiestrogenic, or androgenic effects in mice. Progesterone or pituitary extract given along with the drug did not prevent abortions in mice. The drug was species-specific in that no abortifacient effect was found in rats.     

Antidiabetic potential of Caralluma europaea against alloxan-induced diabetes in mice

Medicinal plants play an important role in the management of diabetes mellitus especially in developing countries where resources are lacking. Herbal of natural origin, unlike the synthetic compounds, are more effective, safer and have less side effects. For continuing research on biological properties of Moroccan medicinal plants, the present work was undertaken to evaluate the potential and mechanism of the antidiabetic activity of the Caralluma europaea methanolic extract in alloxan-induced diabetic mice. A high-performance liquid chromatography technique (HPLC) was used to identify and quantify the major phenolic compounds in the methanolic extract. The in vitro antioxidant property was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging method, reducing power and ß-carotene-linoleic acid assays. The acute toxicity of the extract was evaluated by giving it orally to mice at single doses of 200, 500, 1000, 2000 mg/kg body weight. The antidiabetic effect was conducted on Swiss albino mice. Diabetes was induced with single intraperitonial injection of alloxan monohydrate (200 mg/kg body weight) and animals were treated with methanol extract at a dose of 250 mg/kg and 500 mg/kg body weight. The blood glucose levels were measured and histopathological analysis of pancreas was performed to evaluate alloxan-induced tissue injuries. The main phenols identified and quantified in the extract were ferulic acid, quercetine, 3,4 dihydroxybenzoic acid, rutin, epigallocatechin, and catechin. Ferulic acid was found to be the main phenolic compound ant its proportion was up to 52% of total phenolic compounds, followed by quercetin (36%). The result showed that methanol extract exhibited an antioxidant effect. Acute toxicity studies revealed that C. europaea extract was safe up 2000 mg/kg body weight and approximate LD₅₀ is more than 2000 mg/kg. Moreover, the methanol extract prevented the diabetogenic effect of alloxan and decreased significantly the blood glucose level (P < 0.001) in treated mice. Morphometric study of pancreas revealed that C. europaea extract protected significantly the islets of Langerhans against alloxan-induced tissue alterations.     

Evaluation of Arecoline Hydrobromide Toxicity after a 14-Day Repeated Oral Administration in Wistar Rats

A subchronic toxicity test was conducted in rats on the basis of a previous acute toxicity test to evaluate the safety of arecoline hydrobromide (Ah), to systematically study its pharmacological effects and to provide experimental support for a safe clinical dose. Eighty rats were randomly divided into four groups: a high-dose group (1000 mg/kg), medium-dose group (200 mg/kg), low-dose group (100mg/kg) and blank control group. The doses were administered daily via gastric lavage for 14 consecutive days. There were no significant differences in the low-dose Ah group compared to the control group (P>0.05) with regard to body weight, organ coefficients, hematological parameters and histopathological changes. The high-dose of Ah influenced some of these parameters, which requires further study. The results of this study indicated that a long-term, continuous high dose of Ah was toxic. However, it is safe to use Ah according to the clinically recommended dosing parameters. The level of Ah at which no adverse effects were observed was 100 mg/kg/day under the present study conditions.     

Influence of Griffonia simplicifolia on male sexual behavior in rats: Behavioral and neurochemical study

The seeds of Griffonia simplicifolia Baill. are rich in 5-HTP (5-hydroxytryptophan), a direct precursor of the neurotransmitter serotonin. In the present study we investigated the influence of the plant extract on male sexual behavior. The seed extract was orally administered to Sprague-Dawley male rats at three dose levels (25, 50 and 100 mg/kg) both acutely and subchronically (daily for 9 days). Mating test with receptive female rats was performed 60 min after the acute treatment or the last dose when repetitively administered. Mount, intromission and ejaculation latencies and post-ejaculatory interval were recorded. Food intake and body weight were measured over the 9-day period of treatment. Microdialysis technique was used to detect the extracellular levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in rat brain following the acute administration of the extract dosed at 100 mg/kg. The acute treatment significantly increased mount latency (at any dosage), intromission and ejaculation latencies (at 100 mg/kg) and post-ejaculatory interval (at 50 and 100 mg/kg). On the contrary the subchronic treatment failed to exert a significant influence on copulatory behavior. The daily administration of the extract dosed at 50 and 100 mg/kg for 9 days significantly reduced food intake and body weight. Finally in the microdialysis experiments we found a dramatic increase in 5-HT and its metabolite 5-HIAA.     

Embryo‐Fetal Developmental Toxicity Studies with Pregabalin in Mice and Rabbits

Pregabalin was evaluated for potential developmental toxicity in mice and rabbits. Pregabalin was administered once daily by oral gavage to female albino mice (500, 1250, or 2500 mg/kg) and New Zealand White rabbits (250, 500, or 1250 mg/kg) during organogenesis (gestation day 6 through 15 [mice] or 6 through 20 [rabbits]). Fetuses were evaluated for viability, growth, and morphological development. Pregabalin administration to mice did not induce maternal or developmental toxicity at doses up to 2500 mg/kg, which was associated with a maternal plasma exposure (AUC_0–24) of 3790 μg?hr/ml, ≥30 times the expected human exposure at the maximum recommended daily dose (MRD; 600 mg/day). In rabbits, treatment‐related clinical signs occurred at all doses (AUC_0–24 of 1397, 2023, and 4803 μg?hr/ml at 250, 500, and 1250 mg/kg, respectively). Maternal toxicity was evident at all doses and included ataxia, hypoactivity, and cool to touch. In addition, abortion and females euthanized moribund with total resorption occurred at 1250 mg/kg. There were no treatment‐related malformations at any dose. At 1250 mg/kg, compared with study and historical controls, the percentage of fetuses with retarded ossification was significantly increased and the mean number of ossification sites was decreased, which correlated with decreased fetal and placental weights, consistent with in utero growth retardation. Therefore, the no‐effect dose for developmental toxicity in rabbits was 500 mg/kg, which produced systemic exposure approximately 16‐times human exposure at the MRD. These findings indicate that pregabalin, at the highest dose tested, was not teratogenic in mice or rabbits     

The toxicity of 3-chloropropane-1,2-dipalmitate in Wistar rats and a metabonomics analysis of rat urine by ultra-performance liquid chromatography–mass spectrometry

3-Monochloropropane-1,2-diol(3-MCPD) fatty acid esters can release free 3-MCPD in a certain condition. Free 3-MCPD is a well-known food contaminant and is toxicological well characterized, however, in contrast to free 3-MCPD, the toxicological characterization of 3-MCPD fatty acid esters is puzzling. In this study, toxicological and metabonomics studies of 3-chloropropane-1,2-dipalmitate(3-MCPD dipalmitate) were carried out based on an acute oral toxicity test, a 90-day feeding test and ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) analysis. The LD₅₀ value of 3-MCPD dipalmitate was determined to be 1780 mg/kg body weight (bw) for Wistar rats. The results of the 90-day feeding test in male Wistar rats showed that 3-MCPD dipalmitate caused a significant increase in blood urea nitrogen and creatinine in the high-dose group (267 mg/kg bw/day) compared to control rats. Renal tubular epithelium cell degeneration and renal tubular hyaline cast accumulation were the major histopathological changes in rats administered 3-MCPD dipalmitate. Urine samples obtained after the 90-day feeding test and analyzed by UPLC–MS showed that the differences in metabolic profiles between control and treated rats were clearly distinguished by partial least squares-discriminant analysis (PLS-DA) of the chromatographic data. Five metabolite biomarkers which had earlier and significant variations had been identified, they were first considered to be the early, sensitive biomarkers in evaluating the effect of 3-MCPD dipalmitate exposure, and the possible mechanism of these biomarkers variation was elucidated. The combination of histopathological examination, clinical chemistry and metabolomics analyses in rats resulted in a systematic and comprehensive assessment of the long-term toxicity of 3-MCPD dipalmitate.     

Is Berlina grandiflora (Leguminosae) toxic in rats?

The toxicity profile of the aqueous methanolic extract of Berlina grandiflora (BG) stem bark was studied in rats. The rats were administered graded doses (125-500 mg/kg p.o) of the extract daily for 21 days and the effects on body weight, organ weight, clinical signs, gross pathology, hematology, histology and serum biochemical parameters were measured. The relative weights of the heart, liver, kidneys and lungs of treated rats were unaffected but there were significant changes in the relative weights of the spleen and testes. The packed cell volume and hemoglobin concentrations were slightly reduced whereas total leucocytes counts were increased remarkably. Alkaline phosphatase and Creatine Kinase levels were reduced in all the groups but Glutamate oxaloacetate was significantly elevated. Total proteins and albumin levels remained normal. BG elicited a significant increase in gamma glutamyl transferase concentrations at 250 mg/kg. No significant changes occurred in urea, uric acid and BUN concentrations but calcium levels shot up remarkably. Histological findings did not reveal any treatment-related effects. The acute toxicity LD50 was estimated to be >2000 mg/kg but dose-related mortality rates of 16.7, 33.4 and 50% were observed during the sub-acute toxicity studies. These findings have once more highlighted the limitations of acute toxicity LD50 testing and suggest that BG may exert varied toxicological effects when administered orally in rats.     

The effect of caffeine in the in vivo SCE and micronucleus mutagenicity tests

Caffeine which was administered per os to outbred mice either twice, 30 and 6 h before sacrifice or once, 30 h before sacrifice, at dose levels of 50, 75 or 100 mg/kg body weight only caused a weak induction of micronuclei at the highest dose. Again a level of 100 mg caffeine per kg body weight was required before a weak but not significant effect could be observed in the micronucleus test using a mutagen-sensitive inbred strain of mice. In Chinese hamsters caffeine doses of 45, 75, 150 or 300 mg/kg body weight either given once or twice per os at the same time schedule as used for the mice also caused a clear cut induction of micronuclei only at the highest dose level. In the SCE test with Chinese hamster again 300 mg of caffeine were necessary to obtain a mutagenic effect although this test is considered to be more sensitive to mutagenic damage than the micronucleus test. It can therefore be concluded that caffeine causes DNA damage only at dose levels in the LD50 range which is higher for hamsters than for mice.     

Acute toxicity of Orthosiphon stamineus Benth standardized extract in Sprague Dawley rats

The acute toxicity of standardized extract of Orthosiphon stamineus was studied in Sprague Dawley rats. The rats were administered a single dose of 5000 mg/kg body weight (BW) orally on Day 0 and observed for 14 days. There were no deaths recorded and the animals did not show signs of toxicity during the experimental period. The effect of the extract on general behavior, BW, food and water intake, relative organ weight per 100 g BW, hematology and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control. The acute toxicity LD₅₀ was estimated to be >5000 mg/kg BW.     

Toxicological Study and Oxidative Stress Evaluation for Safety Assessment of <Emphasis Type="Italic">Bacillus thuringiensis</Emphasis> Vip3Aa16 Toxin in Adult Mice

Vegetative insecticidal proteins were produced by some Bacillus thuringiensis strains and were successfully used in biological control against different agricultural pests such as Lepidoptera. To assess the safety of Vip3Aa16 toxins in mammalian organisms, we evaluated their toxicity using histological, hematological, and oxidative stress parameters on albino Swiss mice. The animals were orally treated with 2500, 5000, 7500 milligrams (mg) of the toxin/kilogram (kg) of body weight for 14 days. Then samples of blood, kidney and hepatic tissues were collected at the end of the treatment. Hematological parameters were monitored by RBC, WBC, hemoglobin, hematocrit, MCV, MCH, and MCHC. Liver and kidney MDA, SOD, vitamin C and H₂O₂ were analyzed to assess oxidative damage. Hepatotoxicity was monitored by analysis of the plasma enzymes ALT and AST and bilirubin levels. Renal toxicity was tested by urea, uric acid and creatinine evaluation. The histopathology of kidney and liver tissues was also investigated. The results of the toxicological study revealed that the Vip3AaA16 has no lethal effect since no mortality was observed at any dose. Moreover, body weight, hematological, histological, biochemical and oxidative findings showed no significant differences between treated and control groups. All these findings confirmed that this toxin is highly safe and doesn’t represent any risk on animal health and subsequently, Vip3Aa16 toxin can be safely used in biological programs to control Lepidopteran pests attacking crops around the world.     

Arctigenic acid,the key substance responsible for the hypoglycemic activity of Fructus Arctii

We have reported the antidiabetic activity of the total lignans from Fructus arctii (TLFA) against alloxan-induced diabetes in mice and rats. In this study, arctigenic acid was found to be the main metabolite in rat plasma detected by UPLC/MS and HPLC/MS/MS after oral administration of TLFA. For the first time, its hypoglycemic activity and acute oral toxicity were evaluated in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and ICR mice respectively.GK rats were orally given arctigenic acid (50 mg/kg) twice daily before each meal for 12 weeks. The treatment reduced the elevated plasma glucose, glycosylated hemoglobin and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. We found that the hypoglycemic effect of arctigenic acid was partly due to the stimulation on insulin secretion, whereas the body weight was not affected by arctigenic acid administration in GK rats. Meanwhile, there was no observable acute toxicity of arctigenic acid treatment at the dosage of 280 mg/kg body weight daily in the acute 14-day toxicity study in mice.This study demonstrates that arctigenic acid may be the main metabolite in the rat serum after oral administration of TLFA, which showed significant hypoglycemic effect in GK rats, and low acute toxicity in ICR mice. The result prompts us that arctigenic acid is the key substance responsible for Fructus Arctii antidiabetic activity and it has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.