UNLOCKING SAFE REMEDIES: Preclinical Toxicological Evaluation of the Hydroethanolic Extract of Spondias mombin in Rodents

Background : Toxicity accounts for nearly one-third of candidate drug attrition, underscoring the need for robust preclinical toxicological evaluation early in the drug development pipeline. To the best of our knowledge, this is the first comprehensive toxicological profiling of Spondias mombin hydroethanolic leaf extract in rodent models in Nigeria. Traditionally used for the treatment of dysentery, gonorrhea, wounds, and anemia, S. mombin hydroethanolic extract warrants systematic evaluation to support its safe therapeutic use and guide the optimization of lead compounds. Methods : Acute toxicity was assessed in mice using a limit test following a single oral dose and a 14-day observation period. Subacute and subchronic toxicity were evaluated in female Wistar rats (n = 6/group and n=10/group) administered 40, 200, or 1000 mg/kg/day of extract for 28 and 60 days, respectively. A control group received distilled water. Hematological and biochemical analyses were conducted post-treatment before humane euthanasia. Results : No mortality or observable signs of toxicity were recorded at doses up to 2000 mg/kg. The extract significantly reduced white blood cell count, absolute lymphocytes, and total bilirubin (WBC: 5.60 × 10³/µL vs. 9.35 × 10³/µL; lymphocytes: 2.08 × 10³/µL vs. 4.28 × 10³/µL; bilirubin: 1.99 µmol/L vs. 2.39 µmol/L). S. mombin extract also exhibited dose-dependent increases in red blood cell and hemoglobin counts, alongside reductions in AST, ALT, and ALP levels in the subacute phase. In the subchronic study, S. mombin significantly reduced total cholesterol (40 mg/kg: 1.96 mmol/L vs. control: 2.85 mmol/L) and bilirubin (1000 mg/kg: 10.69 µmol/L vs. control: 22.58 µmol/L). Conclusion : The validated safety profile of S. mombin hydroethanolic leaf extract supports its continued ethnomedicinal use and highlights its promise as a candidate for further pharmacological development—particularly as a potential hematinic, anti-infective, and hepatoprotective agent.