Oral toxicity and genotoxicity assessment of standardized (L.) extract and the pharmacokinetic profile of its active ingredient chicoric acid.

UNLABELLED

(L.), a member of family, has traditionally been used in numerous countries to treat and prevent various immune-related diseases. This study confirmed the oral toxicity and genotoxicity profile of standardized extract under good laboratory practice (GLP) conditions and the pharmacokinetic features of chicoric acid, a major ingredient in extract. For the repeated-dose toxicity test, Sprague Dawley (SD) rats were orally administered 500, 1000, and 2000 mg/kg/day of extract continuously for 13 weeks. The genotoxicity of was determined using standard genotoxicity tests, including bacterial reverse mutations, chromosome aberrations, and micronucleus tests. Additionally, a validated LC-MS/MS method was employed to measure chicoric acid levels in rat plasma for pharmacokinetic analysis. The results of this study indicate that during repeated oral administration of , both male and female SD rats showed no abnormal clinical signs. Furthermore, the genotoxicity tests did not reveal any evidence of genotoxicity in . Pharmacokinetic profile of chicoric acid, following the oral administration of highly purified chicoric acid (95%) and standardized extracts containing 2% chicoric acid, revealed the oral bioavailability to be approximately 1.5%. Increasing the dose of standardized extract (equivalent to 20-100 mg/kg of chicoric acid) from 1 to 5 g/kg resulted in a proportional increase in systemic exposure without reaching saturation. In this study, did not cause oral toxicity and genotoxicity. Additionally, the crude formulation was found to have minimal impact on the pharmacokinetics of chicoric acid.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s43188-024-00238-z.