Toxicological Evaluation of Leaves Aqueous Extract Using Acute and Subacute Toxicity Studies in Mice and Genotoxicity Studies.

is a novel food source and Chinese folk medicine with multiple pharmacological properties. Our previous exploration has demonstrated the antidepressant-like activity of leaves aqueous extract by reliable animal models of depression; however, a lack of toxicological information limits its pharmacological application. The present study aimed to evaluate the preliminary safety of extract by determining acute/subacute toxicity in mice and / genotoxicity. The oral-medium lethal dose of the extract in mice was found to be higher than 5000 mg/kg body weight in the acute toxicity study. In a 14-days subacute toxicity study, extract at doses of 400, 800, and 1600 mg/kg did not result in significant changes in food intake, water intake, body weight, relative organ weight, aspartate aminotransferase activity, alanine aminotransferase activity, creatinine level, and number of white blood cells and red blood cells. However, histopathology observation of organs taken from all mice showed that 1600 mg/kg extract caused slight hydropic degeneration in the cytoplasm of hepatocytes. In a 28-days subacute toxicity study, 600 mg/kg extract significantly increased the level of red blood cells but produced no negative side effects on other pathological parameters. Mice treated with the extract at doses of 200, 400, and 600 mg/kg for 28 days did not manifest any histopathological alterations of the liver, kidney, and spleen. Additionally, the extract showed no chromosomal aberrations in the micronucleus test and chromosomal aberration test. The results revealed that the extract showed no significant toxic effects and no potential genotoxicity but with the likelihood of transient erythrocytosis and slight hepatotoxicity. Further chronic toxicological evaluation involved in more physiological parameters, especially associated with liver toxicity and erythropoietin level, would be needed to determine its safety and application value.