ABSTRACT
To determine the no-observed-adverse-effect level (NOAEL) of exposure and target organs of neem oil for establishing safety criteria for human exposure, the subchronic toxicity study with neem oil in mice was evaluated. The mice (10 per sex for each dose) was orally administered with neem oil with the doses of 0 (to serve as a control), 177, 533 and 1600 mg/kg/day for 90 days. After the treatment period, observation of reversibility or persistence of any toxic effects, mice were continuously fed without treatment for the following 30 days. During the two test periods, the serum biochemistry, organ weight and histopathology were examined. The results showed that the serum biochemistry and organ coefficient in experimental groups had no statistical difference compared with those of the control group. At the 90th day, the histopathological examinations showed that the 1600 mg/kg/day dose of neem oil had varying degrees of damage on each organ except heart, uterus and ovarian. After 30-day recovery, the degree of lesions to the tissues was lessened or even restored. The NOAEL of neem oil was 177 mg/kg/day for mice and the target organs of neem oil were determined to be testicle, liver and kidneys.
Subject(s)
Azadirachta/chemistry , Glycerides/toxicity , Terpenes/toxicity , Toxicity Tests, Subchronic , Administration, Oral , Animals , Dose-Response Relationship, Drug , Eating/drug effects , Female , Glycerides/isolation & purification , Male , Mice , Mice, Inbred Strains , No-Observed-Adverse-Effect Level , Organ Specificity , Plants, Medicinal , Seeds/chemistry , Terpenes/isolation & purificationABSTRACT
Four fractions obtained from alcohol extracts of neem (Azadirachta indica) seed kernel by column chromatography were investigated for antivirus activity against the duck plague virus (DPV) in vitro. Duck embryo fibroblasts (DEF) infected with DPV were treated with the neem seed kernel extracts, and the effect of antivirus was judged by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide colorimetric method assay and direct immunofluorescence assay. The mode of action was tested by the plaque reduction assay. The results showed that fractions 1 to 3 were inactive. The median inhibitory concentration (IC(50)) of fraction 4 was 10.9 µg/mL and inhibited the virus protein expression in the direct immunofluorescence assay. In the plaque reduction assay, fraction 4 could significantly reduce the number of plaques compared with the negative control (P < 0.01) in all modes of action. This study indicated that the fourth fraction obtained from neem seed kernel could improve the viability of infected cells, and reduce the cytopathic effects caused by DPV and the amount of the virus protein expressed in virus-infected cells. The antiviral activity works in the whole process of virus infecting the normal cells.