The Evaluation of the Acute Toxicity and Safety of Verbenalin in ICR Mice

Background: Verbenalin is an iridoid glucoside, which is among the active components of some medicinal herbs such as Verbena officinalis Linn, and Cornus officinalis Siebold and Zucc. Previous studies have confirmed the antioxidant activity and neuroprotective potential of verbenalin. To confirm the safety of verbenalin, an approximate lethal dose was determined based on a single oral dose toxicity study.Methods: Institute of Cancer Research mice were randomly assigned to three verbenalin exposure groups (250, 500, and 1,000 mg/kg) and a control group (5% methylcellulose solution). There were (5 male and 5 female mice per group). Mortality, clinical signs, and body weight were monitored for 14 days, and necropsies were conducted.Results: No mortalities were observed in the control group or the verbenalin 250 mg/kg group, whereas mortalities were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the observation period, stool abnormalities such as mucous stools were observed. Clinical signs such as loss of locomotor activity were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the study period, significant changes in body weight were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups; however, no gross abnormalities were observed at necropsy. Overall, no toxicity was found in the 250 mg/kg group.Conclusion: The approximate lethal dose of verbenalin was estimated to be 500 mg/kg. For a more accurate assessment of the safety of verbenalin, other types of studies such as repeated-dose toxicity studies should also be conducted.