Preclinical safety studies of a SEDDS formulation of the vasorelaxing methanol extract from Crataegus rosei eggl. Leaves.

The present study aimed to assess, via acute and subacute toxicity studies, the safety of the use of the methanol extract obtained from Crataegus rosei leaves as a self-emulsifying drug delivery system (Cr-SEDDS). For the acute toxicity test, female rats were intragastrically administered single 300 and 2000 mg/kg body weight (bw) doses and followed by an observation period of 14 days. For the subacute toxicity study, female and male rats received a daily 300, 500, and 1000 mg/kg bw dose for 28 days. No decrease in food consumption, body weight, signs of apparent toxicity, or deaths were observed. Macro and microscopic necropsies were performed on the main organs, as were blood chemistry, lipidic parameters, and biometry studies. No significant differences in the levels of liver and kidney biomarkers, the levels of red and white blood cells, or structural alterations were observed in the organs of both the treated and control groups. Therefore, the results of these studies demonstrated that the Cr-SEDDS is non-toxic at repeated doses of up to 1000 mg/kg bw. These data enable the establishment of safe dose levels necessary to continue with in vivo pharmacological studies of this SEDDS for the subsequent development of a phytomedicine for the treatment of cardiovascular diseases.