Flavonoid-rich fraction of Croton blanchetianus Baill. (Euphorbiaceae) leaves: Chemical profile, acute and subacute toxicities, genotoxicity and antioxidant potential

Abstract Croton blanchetianus Baill, commonly known as “marmeleiro”, is native to the Brazilian Caatinga is traditional used to treat joint pain and gastrointestinal disorders. The aim of the study was identify the chemical constituents by HPLC-DAD and determine the antioxidant activity of the spray-dried extract (SDE) aqueous (AqF) and ethyl acetate (EAF) fractions obtained from the leaves of C. blanchetianus; and to determine the acute (single dose, 2000 or 5000 mg/kg, p.o) and subacute (repeated dose, 250, 500 and 1000 mg/kg, p.o) toxicities, and genotoxicity (1000 and 2000 mg/kg, p.o) of the EAF in mice. In the acute oral toxicity assay the LD50 was determined as > 5000 mg/kg. In the subacute toxicity, changes in weight gain, food and water intake, hematological, organ coefficients, oxidative stress parameters were not observed; however, changes in transaminases and leukocyte infiltration in the liver were observed at the highest dose. The genotoxicity test showed that high concentrations of EAF were not genotoxic in micronucleus and comet assays. The enrichment process was confirmed by HPLC and five flavonoids were identified. Our results provide evidence that the EAF was safe to use, although a long-term dose of 1000 mg/kg in should be avoided.