Safety evaluation of fermented Platycodon grandiflorus (Jacq.) A.DC. extract: Genotoxicity, acute toxicity, and 13-week subchronic toxicity study in rats

Platycodon grandiflorus (Jacq.) A.DC. is a well-known traditional herbal medicine administered for bronchitis and inflammatory diseases. Especially, anti-inflammatory effect of fermented P. grandiflorus (Jacq.) A.DC. extract (FPGE) was higher than that of P. grandiflorus (Jacq.) A.DC. extract. However, toxicological information for FPGE is lacking. In this study, we establish a toxicological profile for FPGE by testing genotoxicity, acute and 13-week subchronic toxicity. FPGE was evaluated with bacterial reverse mutation, chromosome aberration, and micronucleus test. For the acute- and 13-week subchronic toxicity tests, FPGE was administered orally at doses of 0, 750, 1500, and 3000 mg/kg in SD rats. The results of the genotoxic assays indicated that FPGE induced neither mutagenicity nor clastogenicity. The acute toxicity test showed that FPGE did not affect animal mortality, clinical signs, body weight changes, or microscopic findings at ≤ 3000 mg/kg. The approximate lethal dose (ALD) of FPGE in SD rats was >3000 mg/kg. For the 13-week subchronic toxicity assay, no FPGE dose induced any significant change in mortality, clinical signs, body or organ weight, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination in either SD rat sex. The rat no observed adverse effects level (NOAEL) for FPGE was set to 3000 mg/kg. The present study empirically demonstrated that FPGE has a safe preclinical profile and indicated that it could be safely integrated into health products for atopic dermatitis treatment. [Display omitted] •Anti-inflammatory efficacy of fermented P. grandiflorum extract (FPGE) is well-known.•FPGE did not induce genotoxicity in Ames, CA, and MN test.•In acute toxicity study, the ALD of FPGE was >3000 mg/kg in SD rats.•In 13-week subchoronic toxicity study, the NOAEL of FPGE was 3000 mg/kg in SD rats.