Evaluation of 13-week subchronic toxicity of Platycodon grandiflorus (Jacq.) A.DC. root extract in rats

Ethnopharmacological relevance: Platycodi radix is widely used in traditional herbal medicine for bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. However, data on safety of Platycodi radix are insufficient. Aim of the study: The present study was performed to evaluate the potential subchronic toxicity of Platycodi radix water extract through a 13-week repeated oral dose experiment in Sprague-Dawley rats. Materials and methods: Forty male and 40 female rats were randomly assigned to four experimental groups: three treatment groups receiving 300, 1000, and 3000 mg/kg/day of Platycodi radix water extract and a vehicle control group receiving sterile distilled water for 13 weeks. Results: Repeated oral administration of the Platycodi radix water extract to rats resulted in an increased incidence of centrilobular hepatocellular hypertrophy in the liver, diffuse follicular cell hypertrophy in the thyroid gland, and squamous hyperplasia of the limiting ridge in the stomach at dose levels of >= 500 mg/kg/day of both genders. However, these findings are considered be adaptive non-adverse changes because these findings were observed without organ weight change or clinical pathology alterations. No treatment-related effects on clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, and organ weights were observed at any dose tested. Conclusion: Under the present experimental conditions, the no-observed-adverse-effect level of the Platycodi radix water extract was considered to be >= 3000 mg/kg/day in rats, and no target organs were identified.

Automated summary

The repeated oral administration of Platycodi radix water extract in Sprague-Dawley rats for 13 weeks resulted in increased incidences of hepatocellular hypertrophy in the liver, follicular cell hypertrophy in the thyroid gland, and squamous hyperplasia in the stomach at doses of >= 500 mg/kg/day. However, these changes were considered adaptive non-adverse changes as they were observed without organ weight change or clinical pathology alterations. No treatment-related effects were observed in clinical signs, body weight, food and water consumption, or other parameters at any dose tested.