Prenatal safety evaluation of a standardized dry extract of eugenia uniflora leaves: dissociation between maternal toxicity and fetal outcomes in wistar rats

Abstract

Eugenia uniflora L., Myrtaceae, commonly known as "pitanga" or "pitangueira", is widely used in Brazilian traditional medicine for its antimicrobial, anti-inflammatory, and hypoglycemic properties. However, its safety profile during pregnancy remains poorly understood. This study investigated the potential maternal and developmental toxicity of a standardized dry leaf extract of E. uniflora in Wistar rats. Leaves were oven-dried, extracted by percolation using 44% ethanol, concentrated, and spray-dried. The resulting extract was characterized by moisture content, water activity, and ellagic acid content, quantified by high-performance liquid chromatography with diode-array detection. Pregnant rats (n = 10/ group) received oral doses of 300, 600, or 1200 mg/kg/day, or vehicle, from gestational day 0 to 20. Maternal clinical signs, body weight gain, and food and water intake were monitored daily. On gestational day 21, blood samples were collected for biochemical analysis, and maternal reproductive parameters and genotoxicity were assessed. Fetuses were examined for external, visceral, and skeletal malformations or variations. Phytochemical analysis confirmed ellagic acid as a major constituent. The extract induced dose-dependent reductions in maternal weight gain and food consumption, indicating maternal toxicity. However, no significant effects were observed on reproductive outcomes or fetal development. Implantation rates, resorption frequency, fetal viability, maternal biochemical profiles, and genotoxicity markers remained unaltered. Minor skeletal variations (e.g., delayed ossification) were within the range of normal findings. Visceral anomalies, including palate deformities and ventricular enlargement, were rare and considered gray-zone findings with uncertain toxicological significance. Overall, the extract did not elicit overt developmental toxicity under the tested conditions.