Evaluation of Subacute Toxicity of Hydroethanolic Extracts Combinations from Gnetum africanum (Welv.) and Gnetum buchholzianum (Engl.) (Genetaceae) Leaves: Two Botanical with Antiproliferative and Antioxidant Potential

This study was conducted to assess the toxic effect of hydroethanolic extract combinations of Gnetum africanum Welv. leaves and Gnetum buchholzianum Engl. (Gnetaceae) in experimental rats to test the validity of the treatment of liver disorders related to oxidative stress. The Combinations (m/m) 50-50 for E2 and 75-25 for E3 of ethanol-water extracts from plant leaves at the respective doses of 100, 200, and 400 mg/kg of body weight were used for 32-day toxicity. They were obtained after harvesting leaves, sorting, drying in the air cover for three weeks, and grinding. The resulting powder was doubly macerated with 70% ethanol for 48 hours and filtered. The filtrate was concentrated with the Heidolph-brand rotary rotavapor and each extract obtained was preserved. The administrations were carried out by gavage to wistar, male and non-pregnant female albino rats. In the end, the animals were sacrificed. The serum and organ homogenates were obtained for biochemical, tissue, and histopathological analyses respectively. The analyses revealed insignificant variations at the 5% probability threshold of the weight growth of experimental animals. These variations were found to be statistically significant at the same probability for biochemical and tissue parameters based on the dose of plant extracts and compared to control animals. Histopathological analysis of liver tissue showed leukodate infiltration that indicates extract-induced inflammation of the hepatocytes at the 400 mg/kg dose of body weight in females. However, this infiltration of the cells would have improved the regeneration of hepatocytes justified by the normal rate of transaminases. These results showed that combinations of hydroethanolic extracts of G. africanum and G. buchholzianumare non-toxicand may be potential candidates in the Cameroonian flora medicinal plant database shown in the monitoring of oxidative stress-related diseases.

Evaluation of acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. in Wistar rats

Objective： This study investigated the acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. （AEVM） in rats for evaluating its safety profile. Methods： AEVM for the acute （2000 and 5000 mg/kg） and subacute （200, 400 and 600 mg/kg） toxicity studies was administered orally to rats according the guidelines 425 and 407 of Organization for Economic Cooperation and Development, respectively. Food and water intake as well as body and organ weight of animals were recorded. Signs of toxicity were assessed, and hematological, biochemical and histopathological analyses were performed. Results： In the acute toxicity study, a single dose of the aqueous extract at 2000 or 5000 mg/kg caused no mortality in the animals, suggesting that the median lethal dose is greater than 5000 mg/kg. In the subacute toxicity study, administration of the extract for 28 d, at all doses, caused no significant changes in the body weights or organ weights of rats in the treated groups when compared with the control group. In addition, hematological and biochemical parameters also revealed no toxic effects of the extract on rats. Histological sections of the heart, liver and kidney from test animals showed no signs of degen- eration. Conclusion： These results showed that AEVM at dosage levels up to 600 mg/kg is nontoxic and could also offer protection on some body tissues. AEVM could, therefore, be considered safe.

Metabonomics study of liver and kidney subacute toxicity induced by garidi-5 in rats

Objective:Metabonomics was used to analyze and explore the biomarkers and possible mechanisms of liver and kidney subacute toxicity induced by garidi-5 in rats.Methods:Taking garidi-5 as the target drug and SD rats as the research objects,each administration group except the normal group was intragastric administration of the corresponding drug solution for28 d.The serum,liver and kidney samples of rats were detected by metabolomics and characterized by principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA)to identify the sensitive markers and metabolic pathways of liver and kidney subacute toxicity.Results:Metabolomics analysis showed that compared with the normal group(Z),the 52,64 and 54 different metabolites were identified in the serum,liver and kidney samples of garidi-5 high dose group(GG),which were mainly enriched in ABC transporters,arginine and proline metabolism,nicotinate and nicotinamide metabolism,central carbon metabolism in cancer pathways.Conclusion:The preliminarily suggested that garidi-5 can damage the liver and kidney by affecting the ABC transporters,arginine and proline metabolism,nicotinate and nicotinamide metabolism pathways,etc.Trimethylamine N-oxide,L-pyroglutamic acid,glycine-betaine,xanthine,glutathione,L-leucine,cytidine,L-arginine,spermidine,urea,5-aminovaleric acid,creatine,L-glutamic acid,1-methylnicotinamide and S-adenosyl-L-methionine can be used as potential biomarkers of liver and kidney toxicity sensitivity.

Phytochemical composition and toxicity assessment of Ammi majus L.

Objective:To assess the acute and subacute toxicity as well as the phytochemical composition of two extracts and three fractions of Ammi majus L.Methods:The aqueous extracts were prepared separately by maceration for 48 h and by infusion for 1 h,while the fractions were prepared by the Soxhlet extractor,successively employing cyclohexane,ethyl acetate,and ethanol.The acute toxicity study was carried out in accordance with the OECD N°423 guideline at a single dose(2000 mg/kg)in mice for 14 days.The subacute toxicity study was performed by a daily oral administration of 250 mg/kg 2 for 10 d and 100 mg/kg doses for 28 d.Phytochemical screening was performed using staining and precipitation reactions,while the chemical characterization of some analytes was detected by HPLC-MS/MS analysis.Results:In the acute toxicity study,no signs of toxicity such as convulsion,salivation,diarrhea,sleep and coma were observed during 30 minutes and 14 days,so the lethal dose was higher than 2000 mg/kg for each extract and fraction.The subacute toxicity results showed that at a dose of 250 mg/kg,61.10%of the animals died and the rest developed morbidity.On the other hand,at a dose of 100 mg/kg,all the animals were still alive after 28 days,with no morbidity and the biochemical parameters were normal with no abnormalities in the liver,kidneys and pancreas.Phytochemical screening indicated the presence of flavonoids,tannins,coumarins,and free quinones and the absence of alkaloids and anthocyanins.Conclusions:The extracts and fractions of Ammi majus L.are not toxic in the short and long term with a varied chemical composition.Toxicological tests on animals other than rodents and in the long term(more than 28 days)are needed to further confirm the safety of Ammi majus extracts.

Acute and subacute oral toxicity of Litsea elliptica Blume essential oil in rats

Litsea elliptica Blume has been traditionally used to treat headache,fever,and stomach ulcer,and has also been used as an insect repellent.The acute and subacute toxicities of L.elliptica essential oil were evaluated orally by gavage in female Sprague-Dawley rats.For the acute toxicity study,L.elliptica essential oil was administered in doses from 500 to 4 000 mg/kg(single dose),and in the subacute toxicity test,the following doses were used:125,250,and 500 mg/kg,for 28 consecutive days.In the acute toxicity study,L.elliptica essential oil caused dose-dependent adverse behaviours and mortality.The median lethal dose value was 3 488.86 mg/kg and the acute non-observed-adversed-effect level value was found to be 500 mg/kg.The subacute toxicity study of L.elliptica essential oil did not reveal alterations in body weight,and food and water consumptions.The haematological and biochemical analyses did not show significant differences between control and treated groups in most of the parameters examined,except for the hemoglobin,mean cell hemoglobin concentration,mean cell volume,mean cell hemoglobin,serum albumin,and serum sodium.However,these differences were still within the normal range.No abnormalities or histopathological changes were observed in the liver,pancreatic islet of Langerhans,and renal glomerulous and tubular cells of all treated groups.In conclusion,L.elliptica essential oil can be classified in the U group,which is defined as a group unlikely to present an acute hazard according to World Health Organization(WHO) classification.

Decursin Safety from Root of Angelica gigas in Rats

The subacute intraperitoneal toxicity of decursin was investigated in Spargue-Dawly（SD） rats. The rats were treated with decursin at a dose of 125 and 250 mg·kg-1·day-1for 4 weeks. All animals were observed daily for clinical signs. Their body weights were recorded weekly, no mortality was observed in two doses of 125 and 250 mg·kg-1of decursin. There were no significant differences in the clinical observations, body weight, food and water consumption, hematology, blood chemistry, gross pathological examination or organ weight between control and treated animals of both sexes. In conclusion, no evidence of a subacute toxic potential was observed in this study and no indication for adverse effects was noted at a dose level of 250 mg·kg-1·day-1.