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Acute and sub-chronic toxicity studies of honokiol microemulsion
Qianqian Zhang1, Jianguo Li2, Wei Zhang2
1New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China.
Abstract:
The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication.
Insights
Honokiol microemulsion showed no toxicity up to 500 μg/kg body weight in rats. However, localized vascular irritation at the injection site was observed, requiring attention in clinical use.
Area of Science:
- Pharmacology
- Toxicology
- Nanomedicine
Background:
- Honokiol, a natural compound, is explored for therapeutic potential.
- Microemulsions enhance drug delivery and bioavailability.
- Understanding honokiol microemulsion's safety profile is crucial for clinical application.
Purpose of the Study:
- To evaluate the acute and sub-chronic toxicity of honokiol microemulsion.
- To determine the median lethal dose (LD50) in mice.
- To identify any adverse effects and establish a safe dosage in rats.
Main Methods:
- Acute toxicity: Intravenous injection of graded honokiol microemulsion doses in mice, observed for 14 days.
- Sub-chronic toxicity: Intravenous injection of honokiol microemulsion (100, 500, 2500 μg/kg BW) in rats for 30 days, followed by a 14-day recovery period.
- Examinations included hematology, biochemistry, and histology.
Main Results:
- The median lethal dose (LD50) of honokiol microemulsion in mice was determined to be 50.5 mg/kg body weight.
- The non-toxic reaction dose in rats was established at 500 μg/kg body weight.
- Vascular endothelial cell degeneration and vessel wall changes were noted at the injection site in some animals, but not in other organs.
Conclusions:
- Honokiol microemulsion is considered non-toxic up to a dose of 500 μg/kg body weight.
- The study identified localized vascular irritation at the injection site as a potential concern for clinical use.
- Careful administration is recommended to mitigate injection site reactions during clinical application of honokiol microemulsion.
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